Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes

array:24 ["pii" => "S1578219017302111" "issn" => "15782190" "doi" => "10.1016/j.adengl.2017.06.015" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1659" "copyright" => "Elsevier España, S.L.U. and AEDV" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2017;108:609-19" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1004 "formatos" => array:3 [ "EPUB" => 35 "HTML" => 764 "PDF" => 205 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731017301771" "issn" => "00017310" "doi" => "10.1016/j.ad.2016.12.021" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1659" "copyright" => "AEDV" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2017;108:609-19" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1202 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 843 "PDF" => 357 ] ] "es" => array:14 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:3 [ 0 => "es" 1 => "es" 2 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "609" "paginaFinal" => "619" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 966 "Ancho" => 1333 "Tamanyo" => 85373 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Hernández-Ostiz, L. Prieto-Torres, G. Xirotagaros, L. Noguera-Morel, Á. Hernández-Martín, A. Torrelo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Hernández-Ostiz" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Prieto-Torres" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Xirotagaros" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Noguera-Morel" ] 4 => array:2 [ "nombre" => "Á." "apellidos" => "Hernández-Martín" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Torrelo" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<elsevierMultimedia ident="fig0025"></elsevierMultimedia>" ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219017302111" "doi" => "10.1016/j.adengl.2017.06.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302111?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017301771?idApp=UINPBA000044" "url" => "/00017310/0000010800000007/v2_201708291352/S0001731017301771/v2_201708291352/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219017302147" "issn" => "15782190" "doi" => "10.1016/j.adengl.2017.06.017" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1662" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2017;108:620-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 935 "formatos" => array:3 [ "EPUB" => 32 "HTML" => 744 "PDF" => 159 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology–Part 2: Histiocytic, Macrophage Activation, and Vasculitis Syndromes" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "620" "paginaFinal" => "629" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedades autoinflamatorias en dermatología pediátrica. Parte 2: síndromes histiocítico-macrofágicos y síndromes vasculopáticos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1333 "Ancho" => 1320 "Tamanyo" => 262650 ] ] "descripcion" => array:1 [ "en" => "Blau syndrome. Erythematous-violaceous nodules in both pretibial areas, with a very similar appearance to erythema nodosum." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Hernández-Ostiz, G. Xirotagaros, L. Prieto-Torres, L. Noguera-Morel, A. Torrelo" "autores" => array:5 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Hernández-Ostiz" ] 1 => array:2 [ "nombre" => "G." "apellidos" => "Xirotagaros" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Prieto-Torres" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Noguera-Morel" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Torrelo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731017301801" "doi" => "10.1016/j.ad.2016.12.022" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017301801?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302147?idApp=UINPBA000044" "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017302147/v2_201708291348/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219017301877" "issn" => "15782190" "doi" => "10.1016/j.adengl.2017.04.005" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1672" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Actas Dermosifiliogr. 2017;108:608" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 647 "formatos" => array:3 [ "EPUB" => 33 "HTML" => 390 "PDF" => 224 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Commentary" "titulo" => "Other Faces of Darier Disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "608" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Otras caras de la enfermedad de Darier" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. del Rio" "autores" => array:1 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "del Rio" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731017302041" "doi" => "10.1016/j.ad.2017.04.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017302041?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017301877?idApp=UINPBA000044" "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017301877/v2_201708291348/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "609" "paginaFinal" => "619" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "S. Hernández-Ostiz, L. Prieto-Torres, G. Xirotagaros, L. Noguera-Morel, Á. Hernández-Martín, A. Torrelo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Hernández-Ostiz" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Prieto-Torres" ] 2 => array:2 [ "nombre" => "G." "apellidos" => "Xirotagaros" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Noguera-Morel" ] 4 => array:2 [ "nombre" => "Á." "apellidos" => "Hernández-Martín" ] 5 => array:4 [ "nombre" => "A." "apellidos" => "Torrelo" "email" => array:1 [ 0 => "atorrelo@aedv.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Niño Jesús, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1020 "Ancho" => 975 "Tamanyo" => 237937 ] ] "descripcion" => array:1 [ "en" => "DITRA (deficiency of the IL-36 receptor antagonist). Generalized pustular eruption with polycyclic contours on an erythematous base, similar to an outbreak of generalized pustular psoriasis." ] ] ] "textoCompleto" => "IntroductionThe autoinflammatory diseases are a group of diseases characterized largely by inborn errors of the innate immune system that lead to exaggerated, antigen-independent, inflammatory responses. In this respect, they differ from autoimmune diseases, where alterations in the adaptive immune system lead to an increase in antigen-dependent responses. The innate immunity system constitutes the first line of defense against pathogens and other noxious stimuli through the recognition of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and the subsequent activation of multiple inflammatory signaling cascades and the main effector cells of the innate immune system: macrophages, neutrophils, mast cells, and natural killer cells.<a class="elsevierStyleCrossRef" href="#bib0225">1</a> Although all autoinflammatory syndromes have distinctive clinical features, the vast majority are characterized by early onset (in childhood or even during the neonatal period), recurrent episodes of fever, multisystemic inflammation, and a broad spectrum of cutaneous manifestations. Numerous classification systems exist in the literature for hereditary autoinflammatory diseases. In this review, we will focus on the clinicopathologic features of associated skin lesions to facilitate the recognition of these diseases in routine dermatology practice.Urticaria-like SyndromesIn this first section, we will focus on 2 groups of autoinflammatory diseases: cryopyrin-associated periodic syndromes (CAPS) and hereditary periodic fever syndromes, which frequently manifest with urticaria-like lesions and erythematous and edematous plaques.Cryopyrin-associated Periodic SyndromesCAPS encompass a group of 3 allelic disorders: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and CINCA (chronic infantile neurological cutaneous articular syndrome) or NOMID (neonatal-onset multisystem inflammatory disease). The 3 disorders are inherited in an autosomal dominant manner, have variable penetrance, and are all caused by gain-of-function mutations in the NLRP3 (CIAS1) gene. NLRP3 codes for the protein cryopyrin (NALP3 or PYPAF1), which is an essential component of the inflammasome NLRP3. The inflammasome is a protein complex that responds to multiple stimuli by activating a series of intracellular interactions through caspase 1 that end with the production of powerful proinflammatory cytokines, such as interleukin (IL) 1β and IL-18 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The activation of cryopyrin is triggered by the recognition of PAMPs or DAMPs. NLRP3 mutations that have been implicated in CAPS to date are gain-of-function mutations that constitutively activate the NLRP3 inflammasome, leading to an increased production of proinflammatory cytokines (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Familial Cold Autoinflammatory SyndromeFCAS is the least aggressive of the 3 CAPS. Clinical manifestations begin in the first year of life but are often noticeable in the neonatal period. They typically appear within 2 to 7hours of exposure to cold and resolve after approximately 12hours.<a class="elsevierStyleCrossRef" href="#bib0230">2</a> Lesions are not triggered by contact with cold objects.Cutaneous ManifestationsPatients with FCAS tend to develop erythematous edematous papules and plaques similar to those seen in acute urticaria, but with greater symmetry. Skin biopsy shows a predominantly neutrophilic, perivascular dermal infiltrate, contrasting with the predominantly lymphocytic, eosinophilic infiltrate without vasculitis seen in idiopathic urticaria. It should be noted, however, that both FCAS and urticaria exhibit a variable degree of dermal edema and the dominant component of the infiltrate may also vary. Biopsy thus is a very useful diagnostic aid but it is not pathognomic.Associated Clinical ManifestationsIn addition to skin lesions, patients with FCAS typically experience episodes of fever, chills, conjunctival injection, sweating, dizziness, arthromyalgia, fatigue, and headache. Secondary amyloidosis is very rare and is observed in just 2% of patients. Patients may have an elevated peripheral white blood cell count during flares.Muckle-Wells syndromeMuckle-Wells syndrome, also known as urticaria-deafness-amyloidosis syndrome, is similar to FCAS, but it has more severe clinical outcomes. Onset is also common in childhood, but the age of presentation is more variable. Multiple triggers have been described for Muckle-Wells syndrome, the most common of which are heat and cold.Cutaneous ManifestationsThe clinicopathologic features of Muckle-Wells syndrome are similar to those of FCAS. A characteristic finding is urticaria with a predominantly neutrophilic inflammatory infiltrate without edema in the dermis.Associated Clinical ManifestationsAssociated clinical manifestations include headache, aseptic meningitis, conjunctival injection, papillary edema, arthralgia, arthritis, and episodes of fever, which last longer than in FCAS (up to 36hours) and are more intermittent. Patients may also develop progressive sensorineural deafness, which starts in childhood and can progress to complete hearing loss. Between 25% and 33% of patients develop secondary amyloidosis with frequent involvement of the kidneys.<a class="elsevierStyleCrossRef" href="#bib0230">2</a> Laboratory studies during flares typically show elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), thrombocytosis, anemia, and neutrophilic leukocytosis.Neonatal-onset Multisystem Inflammatory Disease/Chronic Infantile Neurological Cutaneous Articular SyndromeNOMID, or CINCAS, is the severest of the CAPS. The first symptoms tend to appear shortly after birth. Neonatal onset has been reported for 70% of patients and almost 100% of patients show symptoms by the age of 6 months.Many cases are sporadic and the germline NLRP3 mutation is present only in 55% to 60% of patients, suggesting the existence of considerable genetic heterogeneity with a wide variety of somatic mutations.<a class="elsevierStyleCrossRefs" href="#bib0235">3,4</a> Because of this considerable heterogeneity, some authors have suggested that patients with suspected CAPS should undergo initial evaluation before being referred for genetic testing. Proposed criteria include a history of at least 3 recurrent episodes of moderate fever and urticaria, an age of under 20 years of age at disease onset, and elevated CRP levels.<a class="elsevierStyleCrossRef" href="#bib0240">4</a>Cutaneous ManifestationsA characteristic skin manifestation of CINCA/NOMID is a migratory nonpruritic urticaria-like eruption that, unlike in other CAPS, persists for lifetime and has no clear triggers such as cold (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Biopsy shows a superficial and deep perivascular mixed inflammatory infiltrate composed of lymphocytes, neutrophils, and eosinophils together with neutrophilic eccrine hidradenitis<a class="elsevierStyleCrossRef" href="#bib0245">5</a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>Associated Clinical ManifestationsNoncutaneous clinical manifestations are more severe in NOMID and can have serious consequences for neurological development. Common manifestations are short recurrent episodes of fever, enlarged lymph nodes, joint symptoms, hepatosplenomegaly, secondary amyloidosis, neurological involvement with cerebral atrophy, mental retardation, chronic aseptic neutrophilic meningitis, seizures, transient hemiplegia, sensorineural deafness, morning headaches, anterior uveitis, increased intracranial pressure, papilledema, and blindness.<a class="elsevierStyleCrossRef" href="#bib0250">6</a> Characteristic facial features such as flattening of the nasal bridge, macrocephaly, a prominent forehead, and ocular hypertelorism may also be seen. The severity of joint disease is variable. Approximately 50% of children develop severe joint deformities in the first year of life due to cartilage overgrowth and bony overgrowth of epiphyses, which can simulate bone tumors in radiological studies. Typical laboratory study findings include elevated acute phase reactants with leukocytosis, thrombocytosis, eosinophilia, and increased immunoglobulin (Ig) levels in serum.Hereditary Periodic Fever SyndromesIn this second group of autoinflammatory diseases, we have included syndromes characterized by the presence of a nonspecific skin eruption in the form of erythematous papules or macules or plaques that are frequently associated with abdominal pain and recurrent episodes of fever, separated by variable periods of time. This variable incidence of febrile episodes is one of the main distinguishing features of hereditary periodic fever syndromes, which consist, on the one hand, of familial Mediterranean fever, Marshall syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis, and mevalonate kinase deficiency) and hyperimmunoglobulinemia D syndrome (HIDS), in which fever tends to last for less than a week, and on the other hand, of tumor necrosis factor receptor-associated syndrome (TRAPS), in which fever can last for several weeks. We will also review PLAID/APLAID, AISLE, and NAIAD in this section.Familial Mediterranean FeverFamilial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory syndrome. It results from mutations in the MEFV gene, which is located on chromosome 16p13 and encodes the pyrin (or marenostrin) protein. Over 200 MEFV mutations have been reported to date, and the most severe cases of FMF are associated with homozygous M694V mutations. Diagnosis, however, is essentially clinical as not all patients with typical FMF manifestations have a mutation in MEFV. It is therefore likely that other factors are involved in the development of FMF, including, possibly, mutations in other genes.Cutaneous ManifestationsPatients typically have a well-delimited, unilateral or bilateral erythematous edematous erysipeloid plaque on the anterior surface of the lower extremities. The plaque is most often located under the knees or on the dorsum of the foot. It generally has a maximum diameter of 15cm and tends to recur at the same site. Purpuric lesions are also observed on the face, trunk, and extremities. Other cutaneous manifestations that are more common in patients with FMF than in the general population are Schönlein-Henoch purpura (5% of children) and polyarthritis nodosum. It is important to note that many patients do not present skin lesions, and when they do, these can be highly variable. Skin biopsy tends to show a predominantly neutrophilic infiltrate with karyorrhexis.Associated Clinical ManifestationsAssociated clinical manifestations tend to present before the age of 30. They consist of recurrent episodes of high fever (38.5°C-40°C) accompanied by severe asthenia, monoarthritis of large joints (mainly affecting the lower extremities), and acute abdominal pain, possibly with peritonitis. These episodes have a mean duration of 1 to 3 days. Apart from peritonitis, patients may develop other types of serositis, such as pleuritis and pericarditis, which both cause chest pain, as well as scrotal pain due to inflammation of the vaginal tunic.<a class="elsevierStyleCrossRef" href="#bib0255">7</a> Neurological involvement is uncommon, although there have been rare reports of meningitis during acute episodes. Chronic meningitis has not been described. Typical serological alterations during acute episodes include leukocytosis and increased acute phase reactants, ESR, CRP, and fibrinogen. ESR and CRP levels remain elevated during flares. This persistent increase reflects the existence of subclinical inflammation, which, if left untreated, often leads to secondary amyloidosis, which is the most common and most serious outcome of FMF.TNF Receptor–Associated Periodic SyndromeTNF is an inflammatory cytokine that has a key role in pyrexia, cachexia, production of other cytokines, expression of adhesion molecules, activation of leukocytes, and resistance to cell pathogens. The TNF receptor (TNFR) acts by antagonizing and regulating the actions of circulating TNF. TRAPS is due to a gain-of-function mutation in the TNFR gene that results in dysregulated TNF production. It is an autosomal dominant disorder with mutations in the TNFRSF1A gene, which codes for TNFR1 (also known as p55 or CD120a). The vast majority of TNFRSF1A mutations identified to date are substitution mutations located at exons 2, 3 and 4 of the gene, which codes for the extracellular domains of TNFR1. De novo mutations have also been described in some patients.Cutaneous ManifestationsCutaneous lesions have been described in 69% to 87% of patients with TRAPS. The most common manifestation (observed in 40% of patients) is a centrifugal migratory erythematous plaque associated with underlying myalgia, explaining why this condition is sometimes referred to as painful erythema. The plaque migrates from a proximal to a distal site in a process that can last minutes or days. The migration often coincides with the spread of the myalgia. On other occasions, lesions present as urticaria-like plaques or a generalized maculopapular erythematous rash that can coalesce into annular or serpiginous plaques, frequently leaving behind significant ecchymosis. Periorbital edema and conjunctivitis can be diagnostic of TRAPS when accompanied by consistent clinical findings. Skin biopsy shows a perivascular, interstitial mononuclear cell infiltrate. There have been rare reports of leukocytoclastic vasculitis and recurrent panniculitis.Associated Clinical ManifestationsClinical manifestations of TRAPS appear more frequently during childhood or adolescence (mean age of 10 years at diagnosis), but they can appear at any time between the first year of life and the sixth decade. Febrile episodes are common and can last for weeks, although on average they last for approximately 2 weeks. Many patients report sudden, intense abdominal pain during febrile episodes. Similarly to in FMF, this pain can be misdiagnosed as acute abdomen, and approximately a third of patients are sent for abdominal surgery. As mentioned, skin lesions in TRAPS are associated with musculoskeletal involvement with severe myalgia. Deep-tissue biopsy shows monocytic fasciitis, which can also be observed by magnetic resonance imaging. Approximately 50% of patients develop eye problems, such as recurrent conjunctivitis or anterior uveitis. Other potential manifestations include arthralgia or arthritis, pleuritis, pericarditis, scrotal pain, headache, ascetic meningitis, optic neuritis, and behavioral changes. Amyloidosis is the most feared outcome in TRAPS. It has been reported in up to 24% of patients with cysteine residue mutations and 2% of patients with noncysteine mutations who do not receive adequate treatment.<a class="elsevierStyleCrossRef" href="#bib0255">7</a> Blood test alterations during febrile episodes include polyclonal gammopathy, leukocytosis, thrombocytosis, increased ESR, PCR, ferritin, serum amyloid A protein, and fibrinogen, which depending on the severity and chronic nature of the condition may not return to normal levels during afebrile periods.Mevalonate Kinase Deficiency–Hyperimmunoglobulin D SyndromeHIDS can be divided into 2 entities: classic HIDS, which is associated with the MVK mutation, and variant HIDS, which does not have this mutation or any biochemical evidence of reduced mevalonate kinase activity. Variant HIDS has been linked to low-penetrance mutations in the TNFRSF1A gene and patients often have more latent symptoms. The mutated gene in classic HIDS is the kinase mevalonate gene, located on chromosome 12q24. IgD levels are typically, though not necessarily, elevated. Furthermore, no correlation has been observed between IgD elevation and disease severity or frequency of flares. Considering that IgD levels may be within normal limits in HIDS, they are probably not directly responsible for its clinical manifestations. Their increase is more likely to be a response to an initial autoinflammatory process triggered by trauma, vaccination, stress, or other factors.Cutaneous ManifestationsSkin lesions occur in 80% of patients with HIDS and can be highly variable. The most common manifestation is a macular or a maculopapular erythematous rash, with varying degrees of confluence, that mainly affects acral sites. Other lesions include urticaria, erythematous papules or nodules, or petechia, and less frequently, lesions similar to those seen in Sweet syndrome, cellulitis type lesions, Henoch-Schönlein purpura, erythema elevatum diutinum, and other forms of vasculitis. Some patients may develop mouth and genital ulcers.Associated Clinical ManifestationsEpisodes of fever and chills tend to appear within the first 4 years of life (before the age of 12 months in 80% of patients) and generally last between 3 and 7 days. They typically recur every 4 to 6 weeks and are often triggered by vaccination, trauma, surgery, or stress. They are also frequently associated with abdominal pain together with diarrhea and vomiting, serositis, headache, hepatosplenomegaly, polyarthralgia, and nonerosive large-joint arthritis. Many patients with HIDS have soft, swollen bilateral cervical lymph nodes. Blood tests show increased acute phase reactants, leukocytosis, and neutrophilia. IgD serum levels are persistently elevated (≥100U/mL) in over 90% of patients, and 80% of these also have increased IgA (≥260mg/dL). Elevated IgD levels, however, are not specific to HIDS (they are also found in FMF and TRAPS) and as already mentioned, IgD may even be within normal ranges in HIDS, particularly in patients younger than 3 years old.<a class="elsevierStyleCrossRef" href="#bib0255">7</a> A moderate increase in mevalonic acid may be observed in urine during flares.PLCG2-associated Antibody Deficiency and Immune Dysregulation and Autoinflammation PLCG2-associated Antibody Deficiency and Immune DysregulationPLAID syndrome (PLCG2-associated antibody deficiency and immune dysregulation), also known as familial atypical cold urticaria, is a recently described disorder associated with immunodeficiency, hypogammaglobulinemia, and autoimmune disease caused by deletions in the phospholipase C, gamma-2 (PLCG2) gene. Patients present with urticaria, erythema, burning, and granulomas after exposure to cold and they may also have fever, recurrent sinusitis and lung infections, asthma, and autoimmune disorders. Laboratory studies show increased IgE, decreased circulating IgM, IgG, IgA, and CD19+ B cells, and positive antinuclear antibodies (ANAs).APLAID syndrome (autoinflammation PLCG2-associated antibody deficiency and immune dysregulation) is similar to PLAID, but is additionally associated with autoinflammatory disorders caused by point mutations in PLCG2. Clinical manifestations include bronchiolitis, recurrent lung infections, cellulitis, arthralgia, enterocolitis, mild immunodeficiency without autoantibodies, and serious eye problems such as corneal erosions, blisters, ulcers, ocular hypertension, and cataracts. Laboratory studies show similar findings to in PLAID, but the ANAs are negative. The PLCC2 mutation in PLAID is a gain-of-function mutation that results in increased signaling. The mutation responsible for APLAID, by contrast, decreases the threshold required for PLCC2 activation. Both syndromes have highly variable cutaneous manifestations, ranging from cold-induced urticaria-like lesions to vesicular-pustular eruptions that worsen with heat and may be seen in both entities. Fixed granulomatous rashes are more common in PLAID, while vesicular-bullous eruptions and recurrent sterile cellulitis plaques are more common in APLAID. In both syndromes, the histopathologic study shows a dense interstitial, perivascular dermal infiltrate composed of neutrophils, lymphocytes, histiocytes, and eosinophils, and leukocytoclastic vasculitis with prominent karyorrhexis. The mutation described for APLAID causes an increase in intracellular calcium, which could activate the NLRP3 inflammasome, generating IL-1 (which would explain why patients partially respond to treatment with anti-IL-1). Depending on the mutational variants present, patients may develop different phenotypic traits, consisting of both cutaneous and systemic manifestations that may or may not be triggered by cold.<a class="elsevierStyleCrossRefs" href="#bib0260">8,9</a>Autoinflammatory Syndrome With LymphedemaAutoinflammatory syndrome associated with lymphedema (AISLE) is due to mutations in the MDFIC gene, which contains the MyoD family inhibitor domain.Cutaneous ManifestationsThe main cutaneous manifestation of AISLE is an extensive urticaria-like eruption.Associated Clinical ManifestationsOther manifestations include fever accompanied by progressive swelling of the scrotum and lower extremities. Histopathologic examination shows a reduction in the number and size of lymphatic vessels in the area.NLRP1-associated Autoinflammation With Arthritis and DyskeratosisNLRP1-associated autoinflammation with arthritis and dyskeratosis (NAIAD) was described by Grandemange. Constitutive activation of NLRP1 leads to increased activation of caspase 1 and a subsequent increase in IL-18 production.Cutaneous ManifestationsNAIAD is characterized by erythematous-brownish hyperkeratotic papules with a prickly appearance on the trunk and extremities. Dyskeratosis is the main finding and the associated cutaneous manifestations are similar to those seen in phrynoderma, a vitamin A deficiency disorder.Associated Clinical ManifestationsRecurrent fever and arthritis are common in patients with NAIAD.Pustular SyndromesDeficiency of the Interleukin-1-Receptor AntagonistDeficiency of the interleukin-1-receptor antagonist (DIRA) is caused by mutations in IL1RN (IL-1 receptor antagonist) that give rise to a shorter, truncated protein that lacks IL-1 antagonist activity, resulting in the activation of an inflammatory cascade mediated by IL-1 that causes severe bone and skin inflammation.Cutaneous ManifestationsPatients typically present generalized erythematous plaques with superficial pustules, simulating pustular psoriasis, at birth or in the first months of life. There may also be diffuse ichthyosiform scaling that often spares the palms and soles. Mouth ulcers and nail changes in the form of pitting or anonychia are common. Skin biopsy shows subcorneal or spongiform pustules with neutrophils in the epidermis and a dermal neutrophilic infiltrate with variable involvement of the hair follicles, blood vessels, and eccrine glands; immunohistochemical studies show pronounced IL-17 overexpression.<a class="elsevierStyleCrossRef" href="#bib0270">10</a>Associated Clinical ManifestationsFlares tend to be accompanied by fever, conjunctivitis, pulmonary infiltrates with respiratory distress, thrombotic episodes, and characteristic bone alterations, such as periostitis, heterotopic ossifications, cervical spinal fusion, and chronic recurrent sterile multifocal osteomyelitis. This last condition, which frequently affects the epiphyses of the long bones, can cause delayed growth. Blood tests show increased acute phase reactants, mild chronic anemia, and neutrophilic leukocytosis without fever. If the autoinflammatory response is severe enough, it can cause multiorgan failure and death.<a class="elsevierStyleCrossRef" href="#bib0270">10</a> Mutations in DIRA have also been linked to preterm delivery as well as intrauterine multiorgan involvement and death.<a class="elsevierStyleCrossRef" href="#bib0275">11</a>Deficiency of Interleukin-36-Receptor AntagonistMutations associated with deficiency of the IL-36 receptor antagonist (DITRA) have been linked to both familial (recessive autosomal inheritance) and sporadic cases of generalized pustular psoriasis (GPP).Cutaneous ManifestationsCutaneous lesions in DITRA present as an acute generalized pustular eruption on an erythematous base<a class="elsevierStyleCrossRef" href="#bib0280">12</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>), similar to that seen in a GPP flare. DITRA lesions are also characterized by recurrent bouts followed by diffuse superficial scaling. In some cases, the lesions can present as psoriasis vulgaris or pustular acral lesions with nail destruction in the form of continuous acrodermatitis. It is possible that many patients who experience GPP flares in the absence of previous manifestations of psoriasis vulgaris could have the DITRA mutation. The frequency of flares varies considerably from one patient to the next, and the lesions may become chronic and acquire the form of erythematous plaques without pustules.<a class="elsevierStyleCrossRef" href="#bib0280">12</a> Histopathologic examination shows the typical features of GPP with parakeratosis, psoriasiform acanthosis, and spongiform pustules, and a predominance of CD8+ T cells, CD3+ T cells, and macrophages.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Associated Clinical ManifestationsCutaneous flares have a variable frequency and are associated with high fever, general malaise, and asthenia. Other organs are not affected. Flares generally start in childhood but adult onset has been described. Multiple triggers have been identified and include bacterial and viral infections, menstruation, pregnancy, and drugs, among others. High fever and a poor general state of health are the main distinctive features of DITRA, but involvement in most cases is limited to the skin, unlike in DIRA. Laboratory studies show elevated acute phase reactants and lactate and low levels of albumin, zinc, and calcium.Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, AcnePyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA), also known as familial recurrent arthritis, is a rare autosomal dominant disease characterized by the triad of pyogenic arthritis, pyoderma gangrenosum, and cystic acne. The genetic mutation is located on chromosome 15 q24-25.1, which encodes the proline-serine-threonine phosphatase-interacting protein (PSTPIP1), which has incomplete penetrance and highly variable expression.<a class="elsevierStyleCrossRef" href="#bib0285">13</a> There have been reports of PAPA syndrome in patients without the above genetic mutation, although new mutations are being discovered.<a class="elsevierStyleCrossRefs" href="#bib0290">14,15</a> PSTPIP1 is a cytoskeletal protein that is strongly expressed in hematopoietic cells and modulates the activation of T cells, cytoskeletal organization, and release of IL-1β. The mutation causes IL-1β overproduction.Cutaneous ManifestationsCutaneous manifestations of PAPA syndrome typically begin in childhood but worsen considerably at puberty. They consist of severe forms of cystic acne, pathergy, and recurrent sterile ulcers with elevated violaceous borders that are very similar to those seen in pyoderma gangrenosum. An association has also been reported with psoriasis and rosacea.<a class="elsevierStyleCrossRef" href="#bib0295">15</a>Associated Clinical ManifestationsPatients with PAPA syndrome may develop fever, although episodes are inconsistent and do not appear to follow any clear pattern. Fever may be accompanied by recurrent episodes of sterile erosive arthritis. This arthritis may be spontaneous or triggered by minor trauma, and although it tends to disappear after puberty, it occasionally persists into adulthood and is severely disabling. Other less common clinical presentations are recurrent otitis, pharyngeal papillomatosis, lymphadenopathy, splenomegaly, thrombocytopenia, hypergammaglobulinemia, hemolytic anemia, and sulfonamide-induced pancytopenia.Majeed SyndromeMajeed syndrome, like DIRA, is characterized by considerable inflammation of the bones. It responds well to IL-1 antagonists, supporting the hypothesis of an IL-1β-dependent pathogenesis and highlighting the important role of this cytokine in bone inflammation.<a class="elsevierStyleCrossRef" href="#bib0300">16</a> It mainly presents as chronic recurrent multifocal osteomyelitis, neutrophilic dermatosis, and congenital dyserythropoietic anemia with microcytosis. Various homozygous LPIN2 mutations have been identified in patients with Majeed syndrome. The LPIN2 gene encodes a protein that modulates the transcription of coactivators that regulate genes involved in lipid metabolism.Cutaneous ManifestationsSkin lesions are not a characteristic finding in Majeed syndrome. Pustular involvement is more common and there have also been reports of dermatoses similar to those seen in Sweet syndrome and psoriasis.Associated Clinical ManifestationsOsteomyelitis flare-ups are invariably accompanied by high fever, pain, and swelling of the large joints. Foci of osteomyelitis are more common in the clavicles, sternum, and the long bones, and less common in the vertebral bodies and jaw. This chronic inflammation causes delayed growth, low stature, and flexion contractures, and radiographic images show osteolytic lesions and areas of sclerosis.Autoinflammatory Syndrome Associated With Pyrins and Neutrophilic DermatosisAutoinflammatory syndrome associated with pyrins and neutrophilic dermatosis is a new autoinflammatory familial pustular neutrophilic dermatosis described by Masters at the 8th International Congress of Familial Mediterranean Fever and Systemic Auto-Inflammatory Diseases in 2015. It is inherited in an autosomal dominant manner and is caused by monoallelic mutations in the MEFF gene that are different to those involved in FMF, as they affect a highly conserved region of the pyrin protein that constitutes the nexus between this protein and an inhibitory protein known as 14-3-3.Cutaneous ManifestationsCharacteristic cutaneous manifestations are multiple facial pustules and pyoderma gangrenosum–like lesions.<a class="elsevierStyleCrossRef" href="#bib0305">17</a>Associated Clinical ManifestationsThe skin lesions tend to be accompanied by fever, arthromyalgia, and myositis, and increased acute phase reactants.Syndromes With Mucocutaneous UlcersPeriodic Fever Syndrome With Aphthous Stomatitis, Pharyngitis, and AdenitisPeriodic fever syndrome with aphthous stomatitis, pharyngitis, and adenitis, also known as Marshall syndrome, is the most common of all the periodic fever syndromes. It is mostly sporadic and tends to spontaneously resolve within the first decade of life. The episodes occur approximately once a month and generally last between 3 to 6 days. No seasonal patterns have been observed.No genetic defects have been identified to date, although there have been reports of cases with a certain degree of familial aggregation.Cutaneous ManifestationsPatients typically develop small numbers of small aphthous lip or mouth ulcers that heal without scarring, in addition to nonspecific generalized urticaria-like erythema of varying intensity in a small proportion of patients.Associated Clinical ManifestationsAcute recurrent pharyngitis and tonsillitis with negative cultures and enlarged cervical lymph nodes are common. There may also be accompanying constitutional symptoms, such as abdominal pain, headache, arthralgia, cough, nausea, and diarrhea. As with other periodic fever syndromes, blood tests may show elevated acute phase reactants during flares.Periodic Fever Syndrome, Immunodeficiency, and ThrombocytopeniaPeriodic fever, immunodeficiency, and thrombocytopenia (PFIT) is a new autoinflammatory syndrome described by Brogan et al.Cutaneous ManifestationsSevere oral ulcers that result in deforming scarring and microstomia are the main cutaneous manifestation in PFIT.Associated Clinical ManifestationsAdditional clinical features include mouth ulcers, failure to thrive, recurrent infections, and thrombocytopenia.Behçet-like Autoinflammatory Syndrome Associated With A20 HaploinsufficiencyZhou et al.<a class="elsevierStyleCrossRef" href="#bib0310">18</a> published a report on 6 unrelated families with a previously undescribed loss-of-function mutation in the TNFAIP3 gene. This mutation results in haploinsufficiency, which, in turn, leads to an early-onset systemic inflammation syndrome. The mutation causes increased degradation of IkBα, which leads to translocation of NFkB p65 and increased expression of proinflammatory cytokines mediated by this transcription factor.Cutaneous ManifestationsThe clinical manifestations are very similar to those observed in childhood-onset Behçet disease, with oral and genital ulcers.Associated Clinical ManifestationsPatients also frequently develop fever, general malaise, eye inflammation, and early-onset arthralgia and arthritis.Behçet SyndromeBehçet syndrome is a systemic vasculitis that can affect any of the vessels in the body. It is endemic in Eastern Mediterranean countries (Silk Road) and Eastern and Central Asian countries and is associated with HLA-B51.Cutaneous ManifestationsThe clinical manifestations are heterogeneous and consist of erythema nodosum lesions, pustules, necrotizing ulcers, superficial thrombophlebitis and vasculitis, and lesions similar to those seen in pyoderma gangrenosum or Sweet syndrome, among others. It is associated with positive pathergy reactions. Recurrent mouth ulcers are the first manifestation in a high percentage of patients. They tend to be multiple, painful, and heal without leaving a scar, unlike genital ulcers, which leave characteristic flat scars. Neutrophilic vasculitis and/or thrombosis are characteristic histopathologic findings.Associated Clinical ManifestationsEye involvement is the main cause of morbidity in Behçet syndrome. The most common condition is posterior uveitis, but anterior uveitis and uveitis with hypopyon are also observed. Patients may also develop arthritis and a large spectrum of manifestations secondary to systemic vasculitis, such as arterial and venous thrombosis, aneurysms, and digestive and neurological symptoms.Ethical DisclosuresProtection of humans and animalsThe authors declare that no tests were carried out in humans or animals for the purpose of this study.Confidentiality of dataThe authors declare that they have followed their hospital's protocol on the publication of data concerning patients.Right to privacy and informed consentThe authors declare that no private patient data appear in this article.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres888166" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec874138" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres888167" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec874137" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Urticaria-like Syndromes" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Cryopyrin-associated Periodic Syndromes" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0020" "titulo" => "Familial Cold Autoinflammatory Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Associated Clinical Manifestations" ] ] ] 1 => array:3 [ "identificador" => "sec0035" "titulo" => "Muckle-Wells syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Associated Clinical Manifestations" ] ] ] 2 => array:3 [ "identificador" => "sec0050" "titulo" => "Neonatal-onset Multisystem Inflammatory Disease/Chronic Infantile Neurological Cutaneous Articular Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Associated Clinical Manifestations" ] ] ] ] ] 1 => array:3 [ "identificador" => "sec0065" "titulo" => "Hereditary Periodic Fever Syndromes" "secciones" => array:6 [ 0 => array:3 [ "identificador" => "sec0070" "titulo" => "Familial Mediterranean Fever" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Associated Clinical Manifestations" ] ] ] 1 => array:3 [ "identificador" => "sec0085" "titulo" => "TNF Receptor–Associated Periodic Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Associated Clinical Manifestations" ] ] ] 2 => array:3 [ "identificador" => "sec0100" "titulo" => "Mevalonate Kinase Deficiency–Hyperimmunoglobulin D Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0110" "titulo" => "Associated Clinical Manifestations" ] ] ] 3 => array:2 [ "identificador" => "sec0115" "titulo" => "PLCG2-associated Antibody Deficiency and Immune Dysregulation and Autoinflammation PLCG2-associated Antibody Deficiency and Immune Dysregulation" ] 4 => array:3 [ "identificador" => "sec0120" "titulo" => "Autoinflammatory Syndrome With Lymphedema" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0130" "titulo" => "Associated Clinical Manifestations" ] ] ] 5 => array:3 [ "identificador" => "sec0135" "titulo" => "NLRP1-associated Autoinflammation With Arthritis and Dyskeratosis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0140" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0145" "titulo" => "Associated Clinical Manifestations" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0150" "titulo" => "Pustular Syndromes" "secciones" => array:5 [ 0 => array:3 [ "identificador" => "sec0155" "titulo" => "Deficiency of the Interleukin-1-Receptor Antagonist" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0160" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0165" "titulo" => "Associated Clinical Manifestations" ] ] ] 1 => array:3 [ "identificador" => "sec0170" "titulo" => "Deficiency of Interleukin-36-Receptor Antagonist" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0175" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0180" "titulo" => "Associated Clinical Manifestations" ] ] ] 2 => array:3 [ "identificador" => "sec0185" "titulo" => "Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, Acne" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0190" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0195" "titulo" => "Associated Clinical Manifestations" ] ] ] 3 => array:3 [ "identificador" => "sec0200" "titulo" => "Majeed Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0205" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0210" "titulo" => "Associated Clinical Manifestations" ] ] ] 4 => array:3 [ "identificador" => "sec0215" "titulo" => "Autoinflammatory Syndrome Associated With Pyrins and Neutrophilic Dermatosis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0220" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0225" "titulo" => "Associated Clinical Manifestations" ] ] ] ] ] 7 => array:3 [ "identificador" => "sec0230" "titulo" => "Syndromes With Mucocutaneous Ulcers" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0235" "titulo" => "Periodic Fever Syndrome With Aphthous Stomatitis, Pharyngitis, and Adenitis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0240" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0245" "titulo" => "Associated Clinical Manifestations" ] ] ] 1 => array:3 [ "identificador" => "sec0250" "titulo" => "Periodic Fever Syndrome, Immunodeficiency, and Thrombocytopenia" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0255" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0260" "titulo" => "Associated Clinical Manifestations" ] ] ] 2 => array:3 [ "identificador" => "sec0265" "titulo" => "Behçet-like Autoinflammatory Syndrome Associated With A20 Haploinsufficiency" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0270" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0275" "titulo" => "Associated Clinical Manifestations" ] ] ] 3 => array:3 [ "identificador" => "sec0280" "titulo" => "Behçet Syndrome" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0285" "titulo" => "Cutaneous Manifestations" ] 1 => array:2 [ "identificador" => "sec0290" "titulo" => "Associated Clinical Manifestations" ] ] ] ] ] 8 => array:3 [ "identificador" => "sec0295" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0300" "titulo" => "Protection of humans and animals" ] 1 => array:2 [ "identificador" => "sec0305" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0310" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0315" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-01" "fechaAceptado" => "2016-12-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec874138" "palabras" => array:4 [ 0 => "Monogenic autoinflammatory diseases" 1 => "Skin manifestations" 2 => "Classification" 3 => "Histologic diagnosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec874137" "palabras" => array:4 [ 0 => "Enfermedades autoinflamatorias monogenéticas" 1 => "Manifestaciones cutáneas" 2 => "Clasificación" 3 => "Diagnóstico histológico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Monogenic autoinflammatory diseases are a heterogeneous emergent group of conditions that are currently under intensive study. We review the etiopathogenesis of these syndromes and their principal manifestations. Our aim is to propose a classification system based on the clinicopathologic features of typical skin lesions for routine clinical use in dermatology. Our focus is on diagnosis in pediatric practice given that this is the period when the signs and symptoms of these syndromes first appear. In Part 1 we discuss the course of urticaria-like syndromes, which include cryopyrin-associated periodic conditions and hereditary periodic fever syndromes. Pustular syndromes are also covered in this part. Finally, we review the range of therapies available as well as the genetic mutations associated with these autoinflammatory diseases." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Las enfermedades monogénicas autoinflamatorias son un grupo de enfermedades emergentes y heterogéneas en continuo estudio y desarrollo en la actualidad. Nuestro objetivo es revisar estas enfermedades desde el punto de vista de su etiopatogenia y principales manifestaciones, con el fin de proponer una clasificación, basada en las características clinicopatológicas de las lesiones cutáneas típicas, que resulte de utilidad en la práctica clínica habitual de los dermatólogos. El texto está enfocado en el diagnóstico de estos síndromes durante la edad pediátrica, ya que es el periodo habitual de aparición de los primeros síntomas y signos. La primera parte de la revisión se centrará en el desarrollo de los síndromes urticariformes, que incluyen a su vez las criopirinopatías y los síndromes hereditarios asociados a fiebres periódicas, y de los síndromes pustulosos, resumiendo al final del texto las alternativas terapéuticas de estos síndromes autoinflamatorios y sus mutaciones genéticas." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Hernández-Ostiz S, Prieto-Torres L, Xirotagaros G, Noguera-Morel L, Hernández-Martín Á, Torrelo A. Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas. Actas Dermosifiliogr. 2017;108:609–619." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2296 "Ancho" => 3170 "Tamanyo" => 293033 ] ] "descripcion" => array:1 [ "en" => "NLRP3 inflammasome. ASC indicates adaptor protein; CARD, caspase activation and recruitment domain; DAMPS, damage-associated molecular patterns; LRR, leucin-rich repeat; PAMPS, pathogen-associated molecular patterns; PYD, pyrin domain." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 676 "Ancho" => 975 "Tamanyo" => 158379 ] ] "descripcion" => array:1 [ "en" => "NOMID (neonatal-onset multisystem inflammatory disease). Permanent urticaria-like migratory eruption." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1300 "Ancho" => 975 "Tamanyo" => 610096 ] ] "descripcion" => array:1 [ "en" => "NOMID (neonatal-onset multisystem inflammatory disease). Mixed perivascular superficial and deep inflammatory infiltrate associated with a neutrophilic infiltrate in the eccrine gland (hematoxylin-eosin, original magnification ×20)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1020 "Ancho" => 975 "Tamanyo" => 237937 ] ] "descripcion" => array:1 [ "en" => "DITRA (deficiency of the IL-36 receptor antagonist). Generalized pustular eruption with polycyclic contours on an erythematous base, similar to an outbreak of generalized pustular psoriasis." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: AD, autosomal dominant inheritance; APLAID, autoinflammation PLCG2-associated antibody deficiency and immune dysregulation syndrome; AR, autosomal recessive inheritance; CINCA, chronic infantile neurological cutaneous articular syndrome; DIRA, deficiency of the interleukin-1-receptor antagonist DITRA, deficiency of the IL-36 receptor antagonist; HIDS, hyperimmunoglobulinemia D syndrome; IL, interleukin; FMF, familial Mediterranean fever; MWS, Muckle-Wells syndrome; NOMID, neonatal-onset multisystem inflammatory disease; NSAIDs, nonsteroidal anti-inflammatory drugs; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne; PFAPA, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis; PLAID, PLCG2-associated antibody deficiency and immune dysregulation syndrome; TRAPS, tumor necrosis factor receptor-associated syndrome; TNF, tumor necrosis factor." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mutation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FMF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MEFV (AR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pyrin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Of choice: colchicine<a class="elsevierStyleCrossRef" href="#bib0315">19</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250">6,19,20</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(anakinra, rilonacept, canakinumab) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Interferon-alfa, thalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0255">7,19</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HIDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MVK (mevalonate kinase) (AR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mevalonate kinase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRef" href="#bib0315">19</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Colchicine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NSAIDs<a class="elsevierStyleCrossRef" href="#bib0325">21</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Simvastatin<a class="elsevierStyleCrossRefs" href="#bib0330">22,23</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thalidomide<a class="elsevierStyleCrossRef" href="#bib0340">24</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250">6,19,20,25,26</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0315">19,27,28</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TRAPS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNFRSF1A (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF receptor p55 (TNFR1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0315">19,29</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(nonresponse to colchicine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0315">19,29–33</a> IL-1 antagonistas<a class="elsevierStyleCrossRefs" href="#bib0255">7,19,20,25,29,34</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-6 antagonists (tocilizumab)<a class="elsevierStyleCrossRefs" href="#bib0365">29,35,36</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus<a class="elsevierStyleCrossRef" href="#bib0405">37</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PFAPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0315">19,38</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cimetidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Colchicine<a class="elsevierStyleCrossRef" href="#bib0415">39</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tonsillectomy<a class="elsevierStyleCrossRef" href="#bib0420">40</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRef" href="#bib0345">25</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PLAID/APLAID \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PLCG2 (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Phospholipase C gamma 2 (PLCG2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High doses of systemic corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists (partial response)<a class="elsevierStyleCrossRefs" href="#bib0260">8,9</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FCAS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NLRP3/CIAS1 (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cryopyrin (NALP3 or PYPAF1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonexposure to coldIL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0255">7,19,20</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MWS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NLRP3/CIAS1 (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cryopyrin (NALP3 or PYPAF1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250">6,7,19,20,41</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NOMID/CINCA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NLRP3/CIAS1 (AD); some sporadic cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cryopyrin (NALP3 or PYPAF1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0235">3,6,7,19,20,42</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DIRA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1RN(AR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Interleukin-1 receptor antagonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0275">11,19,20,25</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DITRA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-36RN (AR, sporadic cases) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Interleukin-36 receptor antagonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not established<a class="elsevierStyleCrossRef" href="#bib0255">7</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acitretin<a class="elsevierStyleCrossRef" href="#bib0255">7</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical and systemic corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methotrexate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Granulocyte and monocyte apheresis<a class="elsevierStyleCrossRef" href="#bib0435">43</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-antagonists<a class="elsevierStyleCrossRef" href="#bib0440">44</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PSTPIP1/CD2BP1 (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PSTPIP1/CD2BP1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0255">7,19</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporin,<a class="elsevierStyleCrossRef" href="#bib0255">7</a>thalidomide,<a class="elsevierStyleCrossRef" href="#bib0255">7</a> dapsone, tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intravenous immunoglobulin<a class="elsevierStyleCrossRef" href="#bib0255">7</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-antagonists<a class="elsevierStyleCrossRefs" href="#bib0315">19,25</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Combination of isotretinoin and anakinra<a class="elsevierStyleCrossRef" href="#bib0315">19</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0290">14,15,19</a> (possibly treatment of choice) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Majeed Syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LPIN2 (AR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Phosphatidate phosphatase LPIN2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NSAIDs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Corticosteroids, interferon gamma, bisphosphonates \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TNF inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0255">7,16,17,25</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAAND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MEFV gene (AD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pyrin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRef" href="#bib0310">18</a> (1 patient with good response) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1501029.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Genetic Mutations and Treatment Alternatives." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bib0225" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoinflammatory diseases: Clinical and genetic advances" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Farasat" 1 => "I. Aksentijevich" 2 => "J.R. Toro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2008" "volumen" => "144" "paginaInicial" => "392" "paginaFinal" => "402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18347298" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0230" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoinflammatory syndromes for the dermatologist" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Dávila-Seijo" 1 => "A. Hernández-Martín" 2 => "A. Torrelo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clindermatol.2014.02.004" "Revista" => array:6 [ "tituloSerie" => "Clin Dermatol" "fecha" => "2014" "volumen" => "32" "paginaInicial" => "488" "paginaFinal" => "501" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25017460" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0235" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.I. Aróstegui" 1 => "M.D. Lopez Saldaña" 2 => "M. Pascal" 3 => "D. Clemente" 4 => "M. Aymerich" 5 => "F. Balaguer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.27342" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2010" "volumen" => "62" "paginaInicial" => "1158" "paginaFinal" => "1166" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20131270" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0240" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: Epidemiological study and lessons from eight years of genetic analysis in France" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Cuisset" 1 => "I. Jeru" 2 => "B. Dumont" 3 => "A. Fabre" 4 => "E. Cochet" 5 => "J. Le Bozec" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.138420" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "495" "paginaFinal" => "499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21109514" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0245" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cryopyrin-associated periodic syndromes and autoinflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Shinkai" 1 => "T. McCalmont" 2 => "K. Leslie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2007.02540.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2008" "volumen" => "33" "paginaInicial" => "1" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17927785" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0250" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current status of understanding the pathogenesis and management of patients with NOMID/CINCA" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Goldbach-Mansky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11926-011-0165-y" "Revista" => array:6 [ "tituloSerie" => "Curr Rheumatol Rep" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "123" "paginaFinal" => "131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21538043" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0255" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monogenic autoinflammatory diseases: Concept and clinical manifestations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.A. De Jesus" 1 => "R. Goldbach-Mansky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2013.03.016" "Revista" => array:6 [ "tituloSerie" => "Clin Immunol" "fecha" => "2013" "volumen" => "147" "paginaInicial" => "155" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23711932" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0260" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A hypermorphic missense mutation in PLCG2, encoding phospholipase C(2, causes a dominantly inherited autoinflammatory disease with immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Zhou" 1 => "G-S. Lee" 2 => "J. Brady" 3 => "S. Datta" 4 => "M. Katan" 5 => "A. Sheikh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2012.08.006" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2012" "volumen" => "91" "paginaInicial" => "713" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23000145" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0265" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monogenic autoinflammatory diseases: Cytokinopathies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Moghaddas" 1 => "S.L. Masters" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2015.02.012" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2015" "volumen" => "74" "paginaInicial" => "237" "paginaFinal" => "246" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25814341" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0270" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Aksentijevich" 1 => "S.L. Masters" 2 => "P.J. Ferguson" 3 => "P. Dancey" 4 => "J. Frenkel" 5 => "A. van Royen-Kerkhoff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0807865" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "360" "paginaInicial" => "2426" "paginaFinal" => "2437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19494218" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0275" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel mutation in the interleukin-1 receptor antagonist associated with intrauterine disease onset" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Altiok" 1 => "F. Aksoy" 2 => "Y. Perk" 3 => "F. Taylan" 4 => "P.W. Kim" 5 => "B. Ilıkkan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2012.08.003" "Revista" => array:6 [ "tituloSerie" => "Clin Immunol" "fecha" => "2012" "volumen" => "145" "paginaInicial" => "77" "paginaFinal" => "81" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22940634" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0280" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Marrakchi" 1 => "P. Guigue" 2 => "B.R. Renshaw" 3 => "A. Puel" 4 => "X.Y. Pei" 5 => "S. Fraitag" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1013068" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2011" "volumen" => "365" "paginaInicial" => "620" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21848462" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0285" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brief report: Genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.P. Demidowich" 1 => "A.F. Freeman" 2 => "D.B. Kuhns" 3 => "I. Aksentijevich" 4 => "J.I. Gallin" 5 => "M.L. Turner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.34332" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2012" "volumen" => "64" "paginaInicial" => "2022" "paginaFinal" => "2027" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22161697" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0290" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peculiarities of PAPA syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Tallon" 1 => "M. Corkill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/kei178" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2006" "volumen" => "45" "paginaInicial" => "1140" "paginaFinal" => "1143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16527883" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0295" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoinflammatory pustular neutrophilic diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.B. Naik" 1 => "E.W. Cowen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.det.2013.04.001" "Revista" => array:6 [ "tituloSerie" => "Dermatol Clin" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "405" "paginaFinal" => "425" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23827244" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0300" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of anti-IL-1 treatment in Majeed syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Herlin" 1 => "B. Fiirgaard" 2 => "M. Bjerre" 3 => "G. Kerndrup" 4 => "H. Hasle" 5 => "X. Bing" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2012-201818" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2013" "volumen" => "72" "paginaInicial" => "410" "paginaFinal" => "413" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23087183" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0305" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Masters" 1 => "V. Lagou" 2 => "I. Jéru" 3 => "P.J. Baker" 4 => "L. Van Eyck" 5 => "D.A. Parry" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Sci Transl Med" "fecha" => "2016" "volumen" => "8" "paginaInicial" => "332" "paginaFinal" => "345" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0310" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Zhou" 1 => "H. Wang" 2 => "D.M. Schwartz" 3 => "M. Stoffels" 4 => "Y.H. Park" 5 => "Y. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.3459" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2016" "volumen" => "48" "paginaInicial" => "67" "paginaFinal" => "73" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26642243" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0315" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever/Eurotraps Projects. Treatment of autoinflammatory diseases: Results from the Eurofever Registry and a literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Ter Haar" 1 => "H. Lachmann" 2 => "S. Özen" 3 => "P. Woo" 4 => "Y. Uziel" 5 => "C. Modesto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2011-201268" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2013" "volumen" => "72" "paginaInicial" => "678" "paginaFinal" => "685" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22753383" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0320" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IL-1 blockade in autoinflammatory syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Goldbach-Mansky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-med-061512-150641" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Med" "fecha" => "2014" "volumen" => "65" "paginaInicial" => "223" "paginaFinal" => "244" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24422572" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0325" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-steroidal anti-inflammatory drugs in the treatment of hyper-IgD syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Picco" 1 => "M. Gattorno" 2 => "M. Di Rocco" 3 => "A. Buoncompagni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2001" "volumen" => "60" "paginaInicial" => "904" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11534513" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0330" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Simon" 1 => "E. Drewe" 2 => "J.W. van der Meer" 3 => "R.J. Powell" 4 => "R.I. Kelley" 5 => "A.F.H. Stalenhoef" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clpt.2004.01.012" "Revista" => array:6 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "2004" "volumen" => "75" "paginaInicial" => "476" "paginaFinal" => "483" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15116060" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0335" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A patient with hyper-IgD syndrome responding to simvastatin treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Attout" 1 => "S. Guez" 2 => "I. Ranaivo" 3 => "N. Jameerbaccus" 4 => "C. Series" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur J Intern Med" "fecha" => "2008" "volumen" => "19" "paginaInicial" => "82" "paginaFinal" => "83" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0340" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper-IgD and periodic fever syndrome: A randomized, double-blind, placebo controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.P.H. Drenth" 1 => "A.G. Vonk" 2 => "A. Simon" 3 => "R. Powell" 4 => "J.W.M. van der Meer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pharmacol Exp Ther" "fecha" => "2001" "volumen" => "298" "paginaInicial" => "1221" "paginaFinal" => "1226" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11504824" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0345" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treating inflammation by blocking interleukin-1 in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.A. Dinarello" 1 => "J.W. van der Meer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Semin Immunol" "fecha" => "2013" "volumen" => "25" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0350" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "On-demand anakinra treatment is effective in mevalonate kinase deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E.J. Bodar" 1 => "L.M. Kuijk" 2 => "J.P. Drenth" 3 => "J.W. van der Meer" 4 => "A. Simon" 5 => "J. Frenkel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2011.149922" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "2155" "paginaFinal" => "2158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21859689" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0355" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A patient with hyper-IgD syndrome responding to anti-TNF treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Demirkaya" 1 => "M.K. Caglar" 2 => "H.R. Waterham" 3 => "R. Topaloglu" 4 => "S. Ozen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-006-0501-1" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2007" "volumen" => "26" "paginaInicial" => "1757" "paginaFinal" => "1759" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17171314" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0360" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperimmunoglobulinemia D and periodic fever syndrome; treatment with etanercept and follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Topaloğlu" 1 => "N.A. Ayaz" 2 => "H.R. Waterham" 3 => "A. Yüce" 4 => "F. Gumruk" 5 => "O. Sanal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-008-0911-3" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2008" "volumen" => "27" "paginaInicial" => "1317" "paginaFinal" => "1320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18506569" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0365" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "[Progress in classification and treatment for TNF receptor-associated periodic syndrome]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Tsukamoto" 1 => "N. Ueda" 2 => "T. Horiuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Nihon Rinsho Meneki Gakkai Kaishi" "fecha" => "2010" "volumen" => "34" "paginaInicial" => "361" "paginaFinal" => "368" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22041423" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0370" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment with infliximab of a patient with tumor necrosis factor-associated periodic syndrome (TRAPS) who failed to respond to etanercept" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Krelenbaum" 1 => "A. Chaiton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.091094" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2010" "volumen" => "37" "paginaInicial" => "1780" "paginaFinal" => "1782" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20675856" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0375" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of etanercept in the treatment of tumor necrosis factor receptor-associated periodic syndrome: Personal experience and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Cantarini" 1 => "D. Rigante" 2 => "O.M. Lucherini" 3 => "R. Cimaz" 4 => "F. Laghi Pasini" 5 => "C.T. Baldari" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/039463201002300303" "Revista" => array:6 [ "tituloSerie" => "Int J Immunopathol Pharmacol" "fecha" => "2010" "volumen" => "23" "paginaInicial" => "701" "paginaFinal" => "707" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20943039" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0380" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lessons from anti-TNF biologics: infliximab failure in a TRAPS family with the T50M mutation in TNFRSF1A" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Nedjai" 1 => "N. Quillinan" 2 => "R.J. Coughlan" 3 => "L. Church" 4 => "M.F. McDermott" 5 => "G.A. Hitman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/978-1-4419-6612-4_43" "Revista" => array:6 [ "tituloSerie" => "Adv Exp Med Biol" "fecha" => "2011" "volumen" => "691" "paginaInicial" => "409" "paginaFinal" => "419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21153346" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0385" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Failure of sustained response to etanercept and refractoriness to anakinra in patients with T50M TNF-receptor-associated periodic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Quillinan" 1 => "G. Mannion" 2 => "A. Mohammad" 3 => "R. Coughlan" 4 => "L.J. Dickie" 5 => "M.F. McDermott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.144279" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "1692" "paginaFinal" => "1693" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21378401" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0390" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: Dramatic response to Anakinra" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Cattalini" 1 => "A. Meini" 2 => "P. Monari" 3 => "G. Gualdi" 4 => "M. Arisi" 5 => "F. Pelucchi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "20405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24314780" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0395" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of interleukin-6 in a patient with tumor necrosis factor receptor-associated periodic syndrome: Assessment of outcomes following treatment with the anti-interleukin-6 receptor monoclonal antibody tocilizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M. Vaitla" 1 => "P.M. Radford" 2 => "P.J. Tighe" 3 => "R.J. Powell" 4 => "E.M. McDermott" 5 => "I. Todd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.30215" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "1151" "paginaFinal" => "1155" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21225679" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0400" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case presenting with the clinical characteristics of tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) without TNFRSF1A mutations successfully treated with tocilizumab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Hosoya" 1 => "F. Mizoguchi" 2 => "H. Hasegawa" 3 => "K. Miura" 4 => "R. Koike" 5 => "T. Kubota" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2169/internalmedicine.54.3371" "Revista" => array:6 [ "tituloSerie" => "Intern Med" "fecha" => "2015" "volumen" => "54" "paginaInicial" => "2069" "paginaFinal" => "2072" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26278305" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0405" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Succesful treatment using tacrolimus (FK506) in a patient with TNF receptor-associated periodic syndrome (TRAPS) complicated with monocytic fasciitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Ida" 1 => "T. Aramaki" 2 => "K. Arima" 3 => "T. Origuchi" 4 => "A. Kawakami" 5 => "K. Eguchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/kel178" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2006" "volumen" => "45" "paginaInicial" => "1171" "paginaFinal" => "1173" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16801330" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0410" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Documento de Consenso de la Sociedad de Infectología Pediátrica y la Sociedad de Reumatología Pediátrica sobre el diagnóstico diferencial y el abordaje terapéutico de la fiebre recurrente" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Calvo Rey" 1 => "P. Soler-Palacín" 2 => "R. Merino Muñoz" 3 => "J. Saavedra Lozano" 4 => "J. Antón López" 5 => "J.L. Aróstegui" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "An Pediatr (Barc)" "fecha" => "2011" "volumen" => "74" "paginaInicial" => "194e1" "paginaFinal" => "194e16" ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0415" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Tasher" 1 => "M. Stein" 2 => "I. Dalal" 3 => "E. Somekh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1651-2227.2008.00837.x" "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr" "fecha" => "2008" "volumen" => "97" "paginaInicial" => "1090" "paginaFinal" => "1092" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18462461" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0420" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of adenotonsillectomy in PFAPA syndrome: A randomized study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W. Garavello" 1 => "M. Romagnoli" 2 => "R.M. Gaini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jpeds.2009.02.038" "Revista" => array:6 [ "tituloSerie" => "J Pediatr" "fecha" => "2009" "volumen" => "155" "paginaInicial" => "250" "paginaFinal" => "253" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19464029" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0425" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The STING pathway and regulation of innate immune signaling in response to DNA pathogens" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Ishikawa" 1 => "G.N. Barber" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00018-010-0605-2" "Revista" => array:6 [ "tituloSerie" => "Cell Mol Life Sci" "fecha" => "2011" "volumen" => "68" "paginaInicial" => "1157" "paginaFinal" => "1165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21161320" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0430" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P.N. Hawkins" 1 => "H.J. Lachmann" 2 => "E. Aganna" 3 => "M.F. McDermott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.20033" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2004" "volumen" => "50" "paginaInicial" => "607" "paginaFinal" => "612" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14872505" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0435" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case of old age-onset generalized pustular psoriasis with a deficiency of IL-36RN (DITRA) treated by granulocyte and monocyte apheresis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Tominaga" 1 => "M. Yamamoto" 2 => "Y. Imai" 3 => "K. Yamanishi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000380876" "Revista" => array:6 [ "tituloSerie" => "Case Rep Dermatol" "fecha" => "2015" "volumen" => "7" "paginaInicial" => "29" "paginaFinal" => "35" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25848350" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0440" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Rossi-Semerano" 1 => "M. Piram" 2 => "C. Chiaverini" 3 => "D. de Ricaud" 4 => "A. Smahi" 5 => "I. Koné-Paut" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pediatrics" "fecha" => "2013" "volumen" => "132" "paginaInicial" => "1043" "paginaFinal" => "1047" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017302111/v2_201708291348/en/main.assets" "Apartado" => array:4 [ "identificador" => "6177" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Reviews" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010800000007/v2_201708291348/S1578219017302111/v2_201708291348/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302111?idApp=UINPBA000044"]

Estadísticas

Review

Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes

Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas

S. Hernández-Ostiz, L. Prieto-Torres, G. Xirotagaros, L. Noguera-Morel, Á. Hernández-Martín, A. Torrelo

Autor para correspondencia

atorrelo@aedv.es

Corresponding author.

Servicio de Dermatología, Hospital Niño Jesús, Madrid, Spain

Leído

9109

Veces
se ha leído el artículo

2711

Total PDF

6398

Total HTML

Compartir estadísticas

 array:24 [
  "pii" => "S1578219017302111"
  "issn" => "15782190"
  "doi" => "10.1016/j.adengl.2017.06.015"
  "estado" => "S300"
  "fechaPublicacion" => "2017-09-01"
  "aid" => "1659"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and AEDV"
  "copyrightAnyo" => "2017"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "ssu"
  "cita" => "Actas Dermosifiliogr. 2017;108:609-19"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 1004
    "formatos" => array:3 [
      "EPUB" => 35
      "HTML" => 764
      "PDF" => 205
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0001731017301771"
      "issn" => "00017310"
      "doi" => "10.1016/j.ad.2016.12.021"
      "estado" => "S300"
      "fechaPublicacion" => "2017-09-01"
      "aid" => "1659"
      "copyright" => "AEDV"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "ssu"
      "cita" => "Actas Dermosifiliogr. 2017;108:609-19"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 1202
        "formatos" => array:3 [
          "EPUB" => 2
          "HTML" => 843
          "PDF" => 357
        ]
      ]
      "es" => array:14 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "Enfermedades autoinflamatorias en dermatolog&#237;a pedi&#225;trica&#46; Parte 1&#58; s&#237;ndromes urticariformes&#44; s&#237;ndromes pustulosos y s&#237;ndromes con ulceraciones cut&#225;neo-mucosas"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:3 [
          0 => "es"
          1 => "es"
          2 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "609"
            "paginaFinal" => "619"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology-Part 1&#58; Urticaria-like Syndromes&#44; Pustular Syndromes&#44; and Mucocutaneous Ulceration Syndromes"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 1
          "multimedia" => array:5 [
            "identificador" => "fig0025"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => false
            "mostrarDisplay" => true
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "fx1.jpeg"
                "Alto" => 966
                "Ancho" => 1333
                "Tamanyo" => 85373
              ]
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "S&#46; Hern&#225;ndez-Ostiz, L&#46; Prieto-Torres, G&#46; Xirotagaros, L&#46; Noguera-Morel, &#193;&#46; Hern&#225;ndez-Mart&#237;n, A&#46; Torrelo"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "S&#46;"
                "apellidos" => "Hern&#225;ndez-Ostiz"
              ]
              1 => array:2 [
                "nombre" => "L&#46;"
                "apellidos" => "Prieto-Torres"
              ]
              2 => array:2 [
                "nombre" => "G&#46;"
                "apellidos" => "Xirotagaros"
              ]
              3 => array:2 [
                "nombre" => "L&#46;"
                "apellidos" => "Noguera-Morel"
              ]
              4 => array:2 [
                "nombre" => "&#193;&#46;"
                "apellidos" => "Hern&#225;ndez-Mart&#237;n"
              ]
              5 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Torrelo"
              ]
            ]
          ]
        ]
        "resumen" => array:1 [
          0 => array:3 [
            "titulo" => "Graphical abstract"
            "clase" => "graphical"
            "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0025"></elsevierMultimedia></p></span>"
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S1578219017302111"
          "doi" => "10.1016/j.adengl.2017.06.015"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302111?idApp=UINPBA000044"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017301771?idApp=UINPBA000044"
      "url" => "/00017310/0000010800000007/v2_201708291352/S0001731017301771/v2_201708291352/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1578219017302147"
    "issn" => "15782190"
    "doi" => "10.1016/j.adengl.2017.06.017"
    "estado" => "S300"
    "fechaPublicacion" => "2017-09-01"
    "aid" => "1662"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and AEDV"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Actas Dermosifiliogr. 2017;108:620-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 935
      "formatos" => array:3 [
        "EPUB" => 32
        "HTML" => 744
        "PDF" => 159
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology&#8211;Part 2&#58; Histiocytic&#44; Macrophage Activation&#44; and Vasculitis Syndromes"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "620"
          "paginaFinal" => "629"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Enfermedades autoinflamatorias en dermatolog&#237;a pedi&#225;trica&#46; Parte 2&#58; s&#237;ndromes histioc&#237;tico-macrof&#225;gicos y s&#237;ndromes vasculop&#225;ticos"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1333
              "Ancho" => 1320
              "Tamanyo" => 262650
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Blau syndrome&#46; Erythematous-violaceous nodules in both pretibial areas&#44; with a very similar appearance to erythema nodosum&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "S&#46; Hern&#225;ndez-Ostiz, G&#46; Xirotagaros, L&#46; Prieto-Torres, L&#46; Noguera-Morel, A&#46; Torrelo"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Hern&#225;ndez-Ostiz"
            ]
            1 => array:2 [
              "nombre" => "G&#46;"
              "apellidos" => "Xirotagaros"
            ]
            2 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Prieto-Torres"
            ]
            3 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Noguera-Morel"
            ]
            4 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Torrelo"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0001731017301801"
        "doi" => "10.1016/j.ad.2016.12.022"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017301801?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302147?idApp=UINPBA000044"
    "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017302147/v2_201708291348/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1578219017301877"
    "issn" => "15782190"
    "doi" => "10.1016/j.adengl.2017.04.005"
    "estado" => "S300"
    "fechaPublicacion" => "2017-09-01"
    "aid" => "1672"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and AEDV"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "cor"
    "cita" => "Actas Dermosifiliogr. 2017;108:608"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 647
      "formatos" => array:3 [
        "EPUB" => 33
        "HTML" => 390
        "PDF" => 224
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Commentary</span>"
      "titulo" => "Other Faces of Darier Disease"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:1 [
          "paginaInicial" => "608"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Otras caras de la enfermedad de Darier"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "E&#46; del Rio"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "E&#46;"
              "apellidos" => "del Rio"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0001731017302041"
        "doi" => "10.1016/j.ad.2017.04.002"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017302041?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017301877?idApp=UINPBA000044"
    "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017301877/v2_201708291348/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Autoinflammatory Diseases in Pediatric Dermatology-Part 1&#58; Urticaria-like Syndromes&#44; Pustular Syndromes&#44; and Mucocutaneous Ulceration Syndromes"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "609"
        "paginaFinal" => "619"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "S&#46; Hern&#225;ndez-Ostiz, L&#46; Prieto-Torres, G&#46; Xirotagaros, L&#46; Noguera-Morel, &#193;&#46; Hern&#225;ndez-Mart&#237;n, A&#46; Torrelo"
        "autores" => array:6 [
          0 => array:2 [
            "nombre" => "S&#46;"
            "apellidos" => "Hern&#225;ndez-Ostiz"
          ]
          1 => array:2 [
            "nombre" => "L&#46;"
            "apellidos" => "Prieto-Torres"
          ]
          2 => array:2 [
            "nombre" => "G&#46;"
            "apellidos" => "Xirotagaros"
          ]
          3 => array:2 [
            "nombre" => "L&#46;"
            "apellidos" => "Noguera-Morel"
          ]
          4 => array:2 [
            "nombre" => "&#193;&#46;"
            "apellidos" => "Hern&#225;ndez-Mart&#237;n"
          ]
          5 => array:4 [
            "nombre" => "A&#46;"
            "apellidos" => "Torrelo"
            "email" => array:1 [
              0 => "atorrelo&#64;aedv&#46;es"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Ni&#241;o Jes&#250;s&#44; Madrid&#44; Spain"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Enfermedades autoinflamatorias en dermatolog&#237;a pedi&#225;trica&#46; Parte 1&#58; s&#237;ndromes urticariformes&#44; s&#237;ndromes pustulosos y s&#237;ndromes con ulceraciones cut&#225;neo-mucosas"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1020
            "Ancho" => 975
            "Tamanyo" => 237937
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">DITRA &#40;deficiency of the IL-36 receptor antagonist&#41;&#46; Generalized pustular eruption with polycyclic contours on an erythematous base&#44; similar to an outbreak of generalized pustular psoriasis&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The autoinflammatory diseases are a group of diseases characterized largely by inborn errors of the innate immune system that lead to exaggerated&#44; antigen-independent&#44; inflammatory responses&#46; In this respect&#44; they differ from autoimmune diseases&#44; where alterations in the adaptive immune system lead to an increase in antigen-dependent responses&#46; The innate immunity system constitutes the first line of defense against pathogens and other noxious stimuli through the recognition of pathogen-associated molecular patterns &#40;PAMPs&#41; or damage-associated molecular patterns &#40;DAMPs&#41; and the subsequent activation of multiple inflammatory signaling cascades and the main effector cells of the innate immune system&#58; macrophages&#44; neutrophils&#44; mast cells&#44; and natural killer cells&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">1</span></a> Although all autoinflammatory syndromes have distinctive clinical features&#44; the vast majority are characterized by early onset &#40;in childhood or even during the neonatal period&#41;&#44; recurrent episodes of fever&#44; multisystemic inflammation&#44; and a broad spectrum of cutaneous manifestations&#46; Numerous classification systems exist in the literature for hereditary autoinflammatory diseases&#46; In this review&#44; we will focus on the clinicopathologic features of associated skin lesions to facilitate the recognition of these diseases in routine dermatology practice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Urticaria-like Syndromes</span><p id="par0010" class="elsevierStylePara elsevierViewall">In this first section&#44; we will focus on 2 groups of autoinflammatory diseases&#58; cryopyrin-associated periodic syndromes &#40;CAPS&#41; and hereditary periodic fever syndromes&#44; which frequently manifest with urticaria-like lesions and erythematous and edematous plaques&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Cryopyrin-associated Periodic Syndromes</span><p id="par0015" class="elsevierStylePara elsevierViewall">CAPS encompass a group of 3 allelic disorders&#58; familial cold autoinflammatory syndrome &#40;FCAS&#41;&#44; Muckle-Wells syndrome&#44; and CINCA &#40;chronic infantile neurological cutaneous articular syndrome&#41; or NOMID &#40;neonatal-onset multisystem inflammatory disease&#41;<span class="elsevierStyleItalic">&#46;</span> The 3 disorders are inherited in an autosomal dominant manner&#44; have variable penetrance&#44; and are all caused by gain-of-function mutations in the <span class="elsevierStyleItalic">NLRP3</span> &#40;<span class="elsevierStyleItalic">CIAS1</span>&#41; gene&#46; <span class="elsevierStyleItalic">NLRP3</span> codes for the protein cryopyrin &#40;NALP3 or PYPAF1&#41;&#44; which is an essential component of the inflammasome NLRP3&#46; The inflammasome is a protein complex that responds to multiple stimuli by activating a series of intracellular interactions through caspase 1 that end with the production of powerful proinflammatory cytokines&#44; such as interleukin &#40;IL&#41; 1&#946; and IL-18 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The activation of cryopyrin is triggered by the recognition of PAMPs or DAMPs&#46; <span class="elsevierStyleItalic">NLRP3</span> mutations that have been implicated in CAPS to date are gain-of-function mutations that constitutively activate the NLRP3 inflammasome&#44; leading to an increased production of proinflammatory cytokines &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Familial Cold Autoinflammatory Syndrome</span><p id="par0020" class="elsevierStylePara elsevierViewall">FCAS is the least aggressive of the 3 CAPS&#46; Clinical manifestations begin in the first year of life but are often noticeable in the neonatal period&#46; They typically appear within 2 to 7<span class="elsevierStyleHsp" style=""></span>hours of exposure to cold and resolve after approximately 12<span class="elsevierStyleHsp" style=""></span>hours&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">2</span></a> Lesions are not triggered by contact with cold objects&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cutaneous Manifestations</span><p id="par0025" class="elsevierStylePara elsevierViewall">Patients with FCAS tend to develop erythematous edematous papules and plaques similar to those seen in acute urticaria&#44; but with greater symmetry&#46; Skin biopsy shows a predominantly neutrophilic&#44; perivascular dermal infiltrate&#44; contrasting with the predominantly lymphocytic&#44; eosinophilic infiltrate without vasculitis seen in idiopathic urticaria&#46; It should be noted&#44; however&#44; that both FCAS and urticaria exhibit a variable degree of dermal edema and the dominant component of the infiltrate may also vary&#46; Biopsy thus is a very useful diagnostic aid but it is not pathognomic&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Associated Clinical Manifestations</span><p id="par0030" class="elsevierStylePara elsevierViewall">In addition to skin lesions&#44; patients with FCAS typically experience episodes of fever&#44; chills&#44; conjunctival injection&#44; sweating&#44; dizziness&#44; arthromyalgia&#44; fatigue&#44; and headache&#46; Secondary amyloidosis is very rare and is observed in just 2&#37; of patients&#46; Patients may have an elevated peripheral white blood cell count during flares&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Muckle-Wells syndrome</span><p id="par0035" class="elsevierStylePara elsevierViewall">Muckle-Wells syndrome&#44; also known as <span class="elsevierStyleItalic">urticaria-deafness-amyloidosis syndrome</span>&#44; is similar to FCAS&#44; but it has more severe clinical outcomes&#46; Onset is also common in childhood&#44; but the age of presentation is more variable&#46; Multiple triggers have been described for Muckle-Wells syndrome&#44; the most common of which are heat and cold&#46;</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Cutaneous Manifestations</span><p id="par0040" class="elsevierStylePara elsevierViewall">The clinicopathologic features of Muckle-Wells syndrome are similar to those of FCAS&#46; A characteristic finding is urticaria with a predominantly neutrophilic inflammatory infiltrate without edema in the dermis&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Associated Clinical Manifestations</span><p id="par0045" class="elsevierStylePara elsevierViewall">Associated clinical manifestations include headache&#44; aseptic meningitis&#44; conjunctival injection&#44; papillary edema&#44; arthralgia&#44; arthritis&#44; and episodes of fever&#44; which last longer than in FCAS &#40;up to 36<span class="elsevierStyleHsp" style=""></span>hours&#41; and are more intermittent&#46; Patients may also develop progressive sensorineural deafness&#44; which starts in childhood and can progress to complete hearing loss&#46; Between 25&#37; and 33&#37; of patients develop secondary amyloidosis with frequent involvement of the kidneys&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">2</span></a> Laboratory studies during flares typically show elevated erythrocyte sedimentation rate &#40;ESR&#41; and C-reactive protein &#40;CRP&#41;&#44; thrombocytosis&#44; anemia&#44; and neutrophilic leukocytosis&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Neonatal-onset Multisystem Inflammatory Disease&#47;Chronic Infantile Neurological Cutaneous Articular Syndrome</span><p id="par0050" class="elsevierStylePara elsevierViewall">NOMID&#44; or CINCAS&#44; is the severest of the CAPS&#46; The first symptoms tend to appear shortly after birth&#46; Neonatal onset has been reported for 70&#37; of patients and almost 100&#37; of patients show symptoms by the age of 6 months&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Many cases are sporadic and the germline <span class="elsevierStyleItalic">NLRP3</span> mutation is present only in 55&#37; to 60&#37; of patients&#44; suggesting the existence of considerable genetic heterogeneity with a wide variety of somatic mutations&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">3&#44;4</span></a> Because of this considerable heterogeneity&#44; some authors have suggested that patients with suspected CAPS should undergo initial evaluation before being referred for genetic testing&#46; Proposed criteria include a history of at least 3 recurrent episodes of moderate fever and urticaria&#44; an age of under 20 years of age at disease onset&#44; and elevated CRP levels&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">4</span></a></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Cutaneous Manifestations</span><p id="par0060" class="elsevierStylePara elsevierViewall">A characteristic skin manifestation of CINCA&#47;NOMID is a migratory nonpruritic urticaria-like eruption that&#44; unlike in other CAPS&#44; persists for lifetime and has no clear triggers such as cold &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Biopsy shows a superficial and deep perivascular mixed inflammatory infiltrate composed of lymphocytes&#44; neutrophils&#44; and eosinophils together with neutrophilic eccrine hidradenitis<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Associated Clinical Manifestations</span><p id="par0065" class="elsevierStylePara elsevierViewall">Noncutaneous clinical manifestations are more severe in NOMID and can have serious consequences for neurological development&#46; Common manifestations are short recurrent episodes of fever&#44; enlarged lymph nodes&#44; joint symptoms&#44; hepatosplenomegaly&#44; secondary amyloidosis&#44; neurological involvement with cerebral atrophy&#44; mental retardation&#44; chronic aseptic neutrophilic meningitis&#44; seizures&#44; transient hemiplegia&#44; sensorineural deafness&#44; morning headaches&#44; anterior uveitis&#44; increased intracranial pressure&#44; papilledema&#44; and blindness&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">6</span></a> Characteristic facial features such as flattening of the nasal bridge&#44; macrocephaly&#44; a prominent forehead&#44; and ocular hypertelorism may also be seen&#46; The severity of joint disease is variable&#46; Approximately 50&#37; of children develop severe joint deformities in the first year of life due to cartilage overgrowth and bony overgrowth of epiphyses&#44; which can simulate bone tumors in radiological studies&#46; Typical laboratory study findings include elevated acute phase reactants with leukocytosis&#44; thrombocytosis&#44; eosinophilia&#44; and increased immunoglobulin &#40;Ig&#41; levels in serum&#46;</p></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Hereditary Periodic Fever Syndromes</span><p id="par0070" class="elsevierStylePara elsevierViewall">In this second group of autoinflammatory diseases&#44; we have included syndromes characterized by the presence of a nonspecific skin eruption in the form of erythematous papules or macules or plaques that are frequently associated with abdominal pain and recurrent episodes of fever&#44; separated by variable periods of time&#46; This variable incidence of febrile episodes is one of the main distinguishing features of hereditary periodic fever syndromes&#44; which consist&#44; on the one hand&#44; of familial Mediterranean fever&#44; Marshall syndrome &#40;periodic fever&#44; aphthous stomatitis&#44; pharyngitis&#44; adenitis&#44; and mevalonate kinase deficiency&#41; and hyperimmunoglobulinemia D syndrome &#40;HIDS&#41;&#44; in which fever tends to last for less than a week&#44; and on the other hand&#44; of tumor necrosis factor receptor-associated syndrome &#40;TRAPS&#41;&#44; in which fever can last for several weeks&#46; We will also review PLAID&#47;APLAID&#44; AISLE&#44; and NAIAD in this section&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Familial Mediterranean Fever</span><p id="par0075" class="elsevierStylePara elsevierViewall">Familial Mediterranean fever &#40;FMF&#41; is an autosomal recessive autoinflammatory syndrome&#46; It results from mutations in the <span class="elsevierStyleItalic">MEFV</span> gene&#44; which is located on chromosome 16p13 and encodes the pyrin &#40;or marenostrin&#41; protein&#46; Over 200 <span class="elsevierStyleItalic">MEFV</span> mutations have been reported to date&#44; and the most severe cases of FMF are associated with homozygous <span class="elsevierStyleItalic">M694<span class="elsevierStyleHsp" style=""></span>V</span> mutations&#46; Diagnosis&#44; however&#44; is essentially clinical as not all patients with typical FMF manifestations have a mutation in <span class="elsevierStyleItalic">MEFV</span>&#46; It is therefore likely that other factors are involved in the development of FMF&#44; including&#44; possibly&#44; mutations in other genes&#46;</p><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Cutaneous Manifestations</span><p id="par0080" class="elsevierStylePara elsevierViewall">Patients typically have a well-delimited&#44; unilateral or bilateral erythematous edematous erysipeloid plaque on the anterior surface of the lower extremities&#46; The plaque is most often located under the knees or on the dorsum of the foot&#46; It generally has a maximum diameter of 15<span class="elsevierStyleHsp" style=""></span>cm and tends to recur at the same site&#46; Purpuric lesions are also observed on the face&#44; trunk&#44; and extremities&#46; Other cutaneous manifestations that are more common in patients with FMF than in the general population are Sch&#246;nlein-Henoch purpura &#40;5&#37; of children&#41; and polyarthritis nodosum&#46; It is important to note that many patients do not present skin lesions&#44; and when they do&#44; these can be highly variable&#46; Skin biopsy tends to show a predominantly neutrophilic infiltrate with karyorrhexis&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Associated Clinical Manifestations</span><p id="par0085" class="elsevierStylePara elsevierViewall">Associated clinical manifestations tend to present before the age of 30&#46; They consist of recurrent episodes of high fever &#40;38&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C-40<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; accompanied by severe asthenia&#44; monoarthritis of large joints &#40;mainly affecting the lower extremities&#41;&#44; and acute abdominal pain&#44; possibly with peritonitis&#46; These episodes have a mean duration of 1 to 3 days&#46; Apart from peritonitis&#44; patients may develop other types of serositis&#44; such as pleuritis and pericarditis&#44; which both cause chest pain&#44; as well as scrotal pain due to inflammation of the vaginal tunic&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a> Neurological involvement is uncommon&#44; although there have been rare reports of meningitis during acute episodes&#46; Chronic meningitis has not been described&#46; Typical serological alterations during acute episodes include leukocytosis and increased acute phase reactants&#44; ESR&#44; CRP&#44; and fibrinogen&#46; ESR and CRP levels remain elevated during flares&#46; This persistent increase reflects the existence of subclinical inflammation&#44; which&#44; if left untreated&#44; often leads to secondary amyloidosis&#44; which is the most common and most serious outcome of FMF&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">TNF Receptor&#8211;Associated Periodic Syndrome</span><p id="par0090" class="elsevierStylePara elsevierViewall">TNF is an inflammatory cytokine that has a key role in pyrexia&#44; cachexia&#44; production of other cytokines&#44; expression of adhesion molecules&#44; activation of leukocytes&#44; and resistance to cell pathogens&#46; The TNF receptor &#40;TNFR&#41; acts by antagonizing and regulating the actions of circulating TNF&#46; TRAPS is due to a gain-of-function mutation in the <span class="elsevierStyleItalic">TNFR</span> gene that results in dysregulated TNF production&#46; It is an autosomal dominant disorder with mutations in the <span class="elsevierStyleItalic">TNFRSF1A</span> gene&#44; which codes for TNFR1 &#40;also known as <span class="elsevierStyleItalic">p55</span> or <span class="elsevierStyleItalic">CD120a</span>&#41;&#46; The vast majority of <span class="elsevierStyleItalic">TNFRSF1A</span> mutations identified to date are substitution mutations located at exons 2&#44; 3 and 4 of the gene&#44; which codes for the extracellular domains of TNFR1&#46; De novo mutations have also been described in some patients&#46;</p><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Cutaneous Manifestations</span><p id="par0095" class="elsevierStylePara elsevierViewall">Cutaneous lesions have been described in 69&#37; to 87&#37; of patients with TRAPS&#46; The most common manifestation &#40;observed in 40&#37; of patients&#41; is a centrifugal migratory erythematous plaque associated with underlying myalgia&#44; explaining why this condition is sometimes referred to as <span class="elsevierStyleItalic">painful erythema</span>&#46; The plaque migrates from a proximal to a distal site in a process that can last minutes or days&#46; The migration often coincides with the spread of the myalgia&#46; On other occasions&#44; lesions present as urticaria-like plaques or a generalized maculopapular erythematous rash that can coalesce into annular or serpiginous plaques&#44; frequently leaving behind significant ecchymosis&#46; Periorbital edema and conjunctivitis can be diagnostic of TRAPS when accompanied by consistent clinical findings&#46; Skin biopsy shows a perivascular&#44; interstitial mononuclear cell infiltrate&#46; There have been rare reports of leukocytoclastic vasculitis and recurrent panniculitis&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Associated Clinical Manifestations</span><p id="par0100" class="elsevierStylePara elsevierViewall">Clinical manifestations of TRAPS appear more frequently during childhood or adolescence &#40;mean age of 10 years at diagnosis&#41;&#44; but they can appear at any time between the first year of life and the sixth decade&#46; Febrile episodes are common and can last for weeks&#44; although on average they last for approximately 2 weeks&#46; Many patients report sudden&#44; intense abdominal pain during febrile episodes&#46; Similarly to in FMF&#44; this pain can be misdiagnosed as acute abdomen&#44; and approximately a third of patients are sent for abdominal surgery&#46; As mentioned&#44; skin lesions in TRAPS are associated with musculoskeletal involvement with severe myalgia&#46; Deep-tissue biopsy shows monocytic fasciitis&#44; which can also be observed by magnetic resonance imaging&#46; Approximately 50&#37; of patients develop eye problems&#44; such as recurrent conjunctivitis or anterior uveitis&#46; Other potential manifestations include arthralgia or arthritis&#44; pleuritis&#44; pericarditis&#44; scrotal pain&#44; headache&#44; ascetic meningitis&#44; optic neuritis&#44; and behavioral changes&#46; Amyloidosis is the most feared outcome in TRAPS&#46; It has been reported in up to 24&#37; of patients with cysteine residue mutations and 2&#37; of patients with noncysteine mutations who do not receive adequate treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a> Blood test alterations during febrile episodes include polyclonal gammopathy&#44; leukocytosis&#44; thrombocytosis&#44; increased ESR&#44; PCR&#44; ferritin&#44; serum amyloid A protein&#44; and fibrinogen&#44; which depending on the severity and chronic nature of the condition may not return to normal levels during afebrile periods&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Mevalonate Kinase Deficiency&#8211;Hyperimmunoglobulin D Syndrome</span><p id="par0105" class="elsevierStylePara elsevierViewall">HIDS can be divided into 2 entities&#58; classic HIDS&#44; which is associated with the <span class="elsevierStyleItalic">MVK</span> mutation&#44; and variant HIDS&#44; which does not have this mutation or any biochemical evidence of reduced mevalonate kinase activity&#46; Variant HIDS has been linked to low-penetrance mutations in the <span class="elsevierStyleItalic">TNFRSF1A</span> gene and patients often have more latent symptoms&#46; The mutated gene in classic HIDS is the kinase mevalonate gene&#44; located on chromosome 12q24&#46; IgD levels are typically&#44; though not necessarily&#44; elevated&#46; Furthermore&#44; no correlation has been observed between IgD elevation and disease severity or frequency of flares&#46; Considering that IgD levels may be within normal limits in HIDS&#44; they are probably not directly responsible for its clinical manifestations&#46; Their increase is more likely to be a response to an initial autoinflammatory process triggered by trauma&#44; vaccination&#44; stress&#44; or other factors&#46;</p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Cutaneous Manifestations</span><p id="par0110" class="elsevierStylePara elsevierViewall">Skin lesions occur in 80&#37; of patients with HIDS and can be highly variable&#46; The most common manifestation is a macular or a maculopapular erythematous rash&#44; with varying degrees of confluence&#44; that mainly affects acral sites&#46; Other lesions include urticaria&#44; erythematous papules or nodules&#44; or petechia&#44; and less frequently&#44; lesions similar to those seen in Sweet syndrome&#44; cellulitis type lesions&#44; Henoch-Sch&#246;nlein purpura&#44; erythema elevatum diutinum&#44; and other forms of vasculitis&#46; Some patients may develop mouth and genital ulcers&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Associated Clinical Manifestations</span><p id="par0115" class="elsevierStylePara elsevierViewall">Episodes of fever and chills tend to appear within the first 4 years of life &#40;before the age of 12 months in 80&#37; of patients&#41; and generally last between 3 and 7 days&#46; They typically recur every 4 to 6 weeks and are often triggered by vaccination&#44; trauma&#44; surgery&#44; or stress&#46; They are also frequently associated with abdominal pain together with diarrhea and vomiting&#44; serositis&#44; headache&#44; hepatosplenomegaly&#44; polyarthralgia&#44; and nonerosive large-joint arthritis&#46; Many patients with HIDS have soft&#44; swollen bilateral cervical lymph nodes&#46; Blood tests show increased acute phase reactants&#44; leukocytosis&#44; and neutrophilia&#46; IgD serum levels are persistently elevated &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>U&#47;mL&#41; in over 90&#37; of patients&#44; and 80&#37; of these also have increased IgA &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>260<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; Elevated IgD levels&#44; however&#44; are not specific to HIDS &#40;they are also found in FMF and TRAPS&#41; and as already mentioned&#44; IgD may even be within normal ranges in HIDS&#44; particularly in patients younger than 3 years old&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a> A moderate increase in mevalonic acid may be observed in urine during flares&#46;</p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">PLCG2-associated Antibody Deficiency and Immune Dysregulation and Autoinflammation PLCG2-associated Antibody Deficiency and Immune Dysregulation</span><p id="par0120" class="elsevierStylePara elsevierViewall">PLAID syndrome &#40;PLCG2-associated antibody deficiency and immune dysregulation&#41;&#44; also known as <span class="elsevierStyleItalic">familial atypical cold urticaria</span>&#44; is a recently described disorder associated with immunodeficiency&#44; hypogammaglobulinemia&#44; and autoimmune disease caused by deletions in the phospholipase C&#44; gamma-2 &#40;<span class="elsevierStyleItalic">PLCG2</span>&#41; gene&#46; Patients present with urticaria&#44; erythema&#44; burning&#44; and granulomas after exposure to cold and they may also have fever&#44; recurrent sinusitis and lung infections&#44; asthma&#44; and autoimmune disorders&#46; Laboratory studies show increased IgE&#44; decreased circulating IgM&#44; IgG&#44; IgA&#44; and CD19<span class="elsevierStyleSup">&#43;</span> B cells&#44; and positive antinuclear antibodies &#40;ANAs&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">APLAID syndrome &#40;autoinflammation PLCG2-associated antibody deficiency and immune dysregulation&#41; is similar to PLAID&#44; but is additionally associated with autoinflammatory disorders caused by point mutations in <span class="elsevierStyleItalic">PLCG2</span>&#46; Clinical manifestations include bronchiolitis&#44; recurrent lung infections&#44; cellulitis&#44; arthralgia&#44; enterocolitis&#44; mild immunodeficiency without autoantibodies&#44; and serious eye problems such as corneal erosions&#44; blisters&#44; ulcers&#44; ocular hypertension&#44; and cataracts&#46; Laboratory studies show similar findings to in PLAID&#44; but the ANAs are negative&#46; The <span class="elsevierStyleItalic">PLCC2</span> mutation in PLAID is a gain-of-function mutation that results in increased signaling&#46; The mutation responsible for APLAID&#44; by contrast&#44; decreases the threshold required for PLCC2 activation&#46; Both syndromes have highly variable cutaneous manifestations&#44; ranging from cold-induced urticaria-like lesions to vesicular-pustular eruptions that worsen with heat and may be seen in both entities&#46; Fixed granulomatous rashes are more common in PLAID&#44; while vesicular-bullous eruptions and recurrent sterile cellulitis plaques are more common in APLAID&#46; In both syndromes&#44; the histopathologic study shows a dense interstitial&#44; perivascular dermal infiltrate composed of neutrophils&#44; lymphocytes&#44; histiocytes&#44; and eosinophils&#44; and leukocytoclastic vasculitis with prominent karyorrhexis&#46; The mutation described for APLAID causes an increase in intracellular calcium&#44; which could activate the NLRP3 inflammasome&#44; generating IL-1 &#40;which would explain why patients partially respond to treatment with anti-IL-1&#41;&#46; Depending on the mutational variants present&#44; patients may develop different phenotypic traits&#44; consisting of both cutaneous and systemic manifestations that may or may not be triggered by cold&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">8&#44;9</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Autoinflammatory Syndrome With Lymphedema</span><p id="par0130" class="elsevierStylePara elsevierViewall">Autoinflammatory syndrome associated with lymphedema &#40;AISLE&#41; is due to mutations in the <span class="elsevierStyleItalic">MDFIC</span> gene&#44; which contains the MyoD family inhibitor domain&#46;</p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Cutaneous Manifestations</span><p id="par0135" class="elsevierStylePara elsevierViewall">The main cutaneous manifestation of AISLE is an extensive urticaria-like eruption&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Associated Clinical Manifestations</span><p id="par0140" class="elsevierStylePara elsevierViewall">Other manifestations include fever accompanied by progressive swelling of the scrotum and lower extremities&#46; Histopathologic examination shows a reduction in the number and size of lymphatic vessels in the area&#46;</p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">NLRP1-associated Autoinflammation With Arthritis and Dyskeratosis</span><p id="par0145" class="elsevierStylePara elsevierViewall">NLRP1-associated autoinflammation with arthritis and dyskeratosis &#40;NAIAD&#41; was described by Grandemange&#46; Constitutive activation of NLRP1 leads to increased activation of caspase 1 and a subsequent increase in IL-18 production&#46;</p><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Cutaneous Manifestations</span><p id="par0150" class="elsevierStylePara elsevierViewall">NAIAD is characterized by erythematous-brownish hyperkeratotic papules with a prickly appearance on the trunk and extremities&#46; Dyskeratosis is the main finding and the associated cutaneous manifestations are similar to those seen in phrynoderma&#44; a vitamin A deficiency disorder&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Associated Clinical Manifestations</span><p id="par0155" class="elsevierStylePara elsevierViewall">Recurrent fever and arthritis are common in patients with NAIAD&#46;</p></span></span></span></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Pustular Syndromes</span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Deficiency of the Interleukin-1-Receptor Antagonist</span><p id="par0160" class="elsevierStylePara elsevierViewall">Deficiency of the interleukin-1-receptor antagonist &#40;DIRA&#41; is caused by mutations in <span class="elsevierStyleItalic">IL1RN</span> &#40;IL-1 receptor antagonist&#41; that give rise to a shorter&#44; truncated protein that lacks IL-1 antagonist activity&#44; resulting in the activation of an inflammatory cascade mediated by IL-1 that causes severe bone and skin inflammation&#46;</p><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Cutaneous Manifestations</span><p id="par0165" class="elsevierStylePara elsevierViewall">Patients typically present generalized erythematous plaques with superficial pustules&#44; simulating pustular psoriasis&#44; at birth or in the first months of life&#46; There may also be diffuse ichthyosiform scaling that often spares the palms and soles&#46; Mouth ulcers and nail changes in the form of pitting or anonychia are common&#46; Skin biopsy shows subcorneal or spongiform pustules with neutrophils in the epidermis and a dermal neutrophilic infiltrate with variable involvement of the hair follicles&#44; blood vessels&#44; and eccrine glands&#59; immunohistochemical studies show pronounced IL-17 overexpression&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Associated Clinical Manifestations</span><p id="par0170" class="elsevierStylePara elsevierViewall">Flares tend to be accompanied by fever&#44; conjunctivitis&#44; pulmonary infiltrates with respiratory distress&#44; thrombotic episodes&#44; and characteristic bone alterations&#44; such as periostitis&#44; heterotopic ossifications&#44; cervical spinal fusion&#44; and chronic recurrent sterile multifocal osteomyelitis&#46; This last condition&#44; which frequently affects the epiphyses of the long bones&#44; can cause delayed growth&#46; Blood tests show increased acute phase reactants&#44; mild chronic anemia&#44; and neutrophilic leukocytosis without fever&#46; If the autoinflammatory response is severe enough&#44; it can cause multiorgan failure and death&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">10</span></a> Mutations in DIRA have also been linked to preterm delivery as well as intrauterine multiorgan involvement and death&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">11</span></a></p></span></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Deficiency of Interleukin-36-Receptor Antagonist</span><p id="par0175" class="elsevierStylePara elsevierViewall">Mutations associated with deficiency of the IL-36 receptor antagonist &#40;DITRA&#41; have been linked to both familial &#40;recessive autosomal inheritance&#41; and sporadic cases of generalized pustular psoriasis &#40;GPP&#41;&#46;</p><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Cutaneous Manifestations</span><p id="par0180" class="elsevierStylePara elsevierViewall">Cutaneous lesions in DITRA present as an acute generalized pustular eruption on an erythematous base<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">12</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; similar to that seen in a GPP flare&#46; DITRA lesions are also characterized by recurrent bouts followed by diffuse superficial scaling&#46; In some cases&#44; the lesions can present as psoriasis vulgaris or pustular acral lesions with nail destruction in the form of continuous acrodermatitis&#46; It is possible that many patients who experience GPP flares in the absence of previous manifestations of psoriasis vulgaris could have the DITRA mutation&#46; The frequency of flares varies considerably from one patient to the next&#44; and the lesions may become chronic and acquire the form of erythematous plaques without pustules&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">12</span></a> Histopathologic examination shows the typical features of GPP with parakeratosis&#44; psoriasiform acanthosis&#44; and spongiform pustules&#44; and a predominance of CD8<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; and macrophages&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Associated Clinical Manifestations</span><p id="par0185" class="elsevierStylePara elsevierViewall">Cutaneous flares have a variable frequency and are associated with high fever&#44; general malaise&#44; and asthenia&#46; Other organs are not affected&#46; Flares generally start in childhood but adult onset has been described&#46; Multiple triggers have been identified and include bacterial and viral infections&#44; menstruation&#44; pregnancy&#44; and drugs&#44; among others&#46; High fever and a poor general state of health are the main distinctive features of DITRA&#44; but involvement in most cases is limited to the skin&#44; unlike in DIRA&#46; Laboratory studies show elevated acute phase reactants and lactate and low levels of albumin&#44; zinc&#44; and calcium&#46;</p></span></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Pyogenic Sterile Arthritis&#44; Pyoderma Gangrenosum&#44; Acne</span><p id="par0190" class="elsevierStylePara elsevierViewall">Pyogenic sterile arthritis&#44; pyoderma gangrenosum&#44; and acne &#40;PAPA&#41;&#44; also known as <span class="elsevierStyleItalic">familial recurrent arthritis</span>&#44; is a rare autosomal dominant disease characterized by the triad of pyogenic arthritis&#44; pyoderma gangrenosum&#44; and cystic acne&#46; The genetic mutation is located on chromosome 15 q24-25&#46;1&#44; which encodes the proline-serine-threonine phosphatase-interacting protein &#40;PSTPIP1&#41;&#44; which has incomplete penetrance and highly variable expression&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">13</span></a> There have been reports of PAPA syndrome in patients without the above genetic mutation&#44; although new mutations are being discovered&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">14&#44;15</span></a> PSTPIP1 is a cytoskeletal protein that is strongly expressed in hematopoietic cells and modulates the activation of T cells&#44; cytoskeletal organization&#44; and release of IL-1&#946;&#46; The mutation causes IL-1&#946; overproduction&#46;</p><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Cutaneous Manifestations</span><p id="par0195" class="elsevierStylePara elsevierViewall">Cutaneous manifestations of PAPA syndrome typically begin in childhood but worsen considerably at puberty&#46; They consist of severe forms of cystic acne&#44; pathergy&#44; and recurrent sterile ulcers with elevated violaceous borders that are very similar to those seen in pyoderma gangrenosum&#46; An association has also been reported with psoriasis and rosacea&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Associated Clinical Manifestations</span><p id="par0200" class="elsevierStylePara elsevierViewall">Patients with PAPA syndrome may develop fever&#44; although episodes are inconsistent and do not appear to follow any clear pattern&#46; Fever may be accompanied by recurrent episodes of sterile erosive arthritis&#46; This arthritis may be spontaneous or triggered by minor trauma&#44; and although it tends to disappear after puberty&#44; it occasionally persists into adulthood and is severely disabling&#46; Other less common clinical presentations are recurrent otitis&#44; pharyngeal papillomatosis&#44; lymphadenopathy&#44; splenomegaly&#44; thrombocytopenia&#44; hypergammaglobulinemia&#44; hemolytic anemia&#44; and sulfonamide-induced pancytopenia&#46;</p></span></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Majeed Syndrome</span><p id="par0205" class="elsevierStylePara elsevierViewall">Majeed syndrome&#44; like DIRA&#44; is characterized by considerable inflammation of the bones&#46; It responds well to IL-1 antagonists&#44; supporting the hypothesis of an IL-1&#946;-dependent pathogenesis and highlighting the important role of this cytokine in bone inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">16</span></a> It mainly presents as chronic recurrent multifocal osteomyelitis&#44; neutrophilic dermatosis&#44; and congenital dyserythropoietic anemia with microcytosis&#46; Various homozygous <span class="elsevierStyleItalic">LPIN2</span> mutations have been identified in patients with Majeed syndrome&#46; The <span class="elsevierStyleItalic">LPIN2</span> gene encodes a protein that modulates the transcription of coactivators that regulate genes involved in lipid metabolism&#46;</p><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Cutaneous Manifestations</span><p id="par0210" class="elsevierStylePara elsevierViewall">Skin lesions are not a characteristic finding in Majeed syndrome&#46; Pustular involvement is more common and there have also been reports of dermatoses similar to those seen in Sweet syndrome and psoriasis&#46;</p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Associated Clinical Manifestations</span><p id="par0215" class="elsevierStylePara elsevierViewall">Osteomyelitis flare-ups are invariably accompanied by high fever&#44; pain&#44; and swelling of the large joints&#46; Foci of osteomyelitis are more common in the clavicles&#44; sternum&#44; and the long bones&#44; and less common in the vertebral bodies and jaw&#46; This chronic inflammation causes delayed growth&#44; low stature&#44; and flexion contractures&#44; and radiographic images show osteolytic lesions and areas of sclerosis&#46;</p></span></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Autoinflammatory Syndrome Associated With Pyrins and Neutrophilic Dermatosis</span><p id="par0220" class="elsevierStylePara elsevierViewall">Autoinflammatory syndrome associated with pyrins and neutrophilic dermatosis is a new autoinflammatory familial pustular neutrophilic dermatosis described by Masters at the 8th International Congress of Familial Mediterranean Fever and Systemic Auto-Inflammatory Diseases in 2015&#46; It is inherited in an autosomal dominant manner and is caused by monoallelic mutations in the <span class="elsevierStyleItalic">MEFF</span> gene that are different to those involved in FMF&#44; as they affect a highly conserved region of the pyrin protein that constitutes the nexus between this protein and an inhibitory protein known as 14-3-3&#46;</p><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Cutaneous Manifestations</span><p id="par0225" class="elsevierStylePara elsevierViewall">Characteristic cutaneous manifestations are multiple facial pustules and pyoderma gangrenosum&#8211;like lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Associated Clinical Manifestations</span><p id="par0230" class="elsevierStylePara elsevierViewall">The skin lesions tend to be accompanied by fever&#44; arthromyalgia&#44; and myositis&#44; and increased acute phase reactants&#46;</p></span></span></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Syndromes With Mucocutaneous Ulcers</span><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Periodic Fever Syndrome With Aphthous Stomatitis&#44; Pharyngitis&#44; and Adenitis</span><p id="par0235" class="elsevierStylePara elsevierViewall">Periodic fever syndrome with aphthous stomatitis&#44; pharyngitis&#44; and adenitis&#44; also known as <span class="elsevierStyleItalic">Marshall syndrome</span>&#44; is the most common of all the periodic fever syndromes&#46; It is mostly sporadic and tends to spontaneously resolve within the first decade of life&#46; The episodes occur approximately once a month and generally last between 3 to 6 days&#46; No seasonal patterns have been observed&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">No genetic defects have been identified to date&#44; although there have been reports of cases with a certain degree of familial aggregation&#46;</p><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Cutaneous Manifestations</span><p id="par0245" class="elsevierStylePara elsevierViewall">Patients typically develop small numbers of small aphthous lip or mouth ulcers that heal without scarring&#44; in addition to nonspecific generalized urticaria-like erythema of varying intensity in a small proportion of patients&#46;</p></span><span id="sec0245" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Associated Clinical Manifestations</span><p id="par0250" class="elsevierStylePara elsevierViewall">Acute recurrent pharyngitis and tonsillitis with negative cultures and enlarged cervical lymph nodes are common&#46; There may also be accompanying constitutional symptoms&#44; such as abdominal pain&#44; headache&#44; arthralgia&#44; cough&#44; nausea&#44; and diarrhea&#46; As with other periodic fever syndromes&#44; blood tests may show elevated acute phase reactants during flares&#46;</p></span></span><span id="sec0250" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Periodic Fever Syndrome&#44; Immunodeficiency&#44; and Thrombocytopenia</span><p id="par0255" class="elsevierStylePara elsevierViewall">Periodic fever&#44; immunodeficiency&#44; and thrombocytopenia &#40;PFIT&#41; is a new autoinflammatory syndrome described by Brogan et al&#46;</p><span id="sec0255" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0275">Cutaneous Manifestations</span><p id="par0260" class="elsevierStylePara elsevierViewall">Severe oral ulcers that result in deforming scarring and microstomia are the main cutaneous manifestation in PFIT&#46;</p></span><span id="sec0260" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0280">Associated Clinical Manifestations</span><p id="par0265" class="elsevierStylePara elsevierViewall">Additional clinical features include mouth ulcers&#44; failure to thrive&#44; recurrent infections&#44; and thrombocytopenia&#46;</p></span></span><span id="sec0265" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0285">Beh&#231;et-like Autoinflammatory Syndrome Associated With A20 Haploinsufficiency</span><p id="par0270" class="elsevierStylePara elsevierViewall">Zhou et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">18</span></a> published a report on 6 unrelated families with a previously undescribed loss-of-function mutation in the <span class="elsevierStyleItalic">TNFAIP3</span> gene&#46; This mutation results in haploinsufficiency&#44; which&#44; in turn&#44; leads to an early-onset systemic inflammation syndrome&#46; The mutation causes increased degradation of IkB&#945;&#44; which leads to translocation of NFkB p65 and increased expression of proinflammatory cytokines mediated by this transcription factor&#46;</p><span id="sec0270" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0290">Cutaneous Manifestations</span><p id="par0275" class="elsevierStylePara elsevierViewall">The clinical manifestations are very similar to those observed in childhood-onset Beh&#231;et disease&#44; with oral and genital ulcers&#46;</p></span><span id="sec0275" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0295">Associated Clinical Manifestations</span><p id="par0280" class="elsevierStylePara elsevierViewall">Patients also frequently develop fever&#44; general malaise&#44; eye inflammation&#44; and early-onset arthralgia and arthritis&#46;</p></span></span><span id="sec0280" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0300">Beh&#231;et Syndrome</span><p id="par0285" class="elsevierStylePara elsevierViewall">Beh&#231;et syndrome is a systemic vasculitis that can affect any of the vessels in the body&#46; It is endemic in Eastern Mediterranean countries &#40;Silk Road&#41; and Eastern and Central Asian countries and is associated with HLA-B51&#46;</p><span id="sec0285" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0305">Cutaneous Manifestations</span><p id="par0290" class="elsevierStylePara elsevierViewall">The clinical manifestations are heterogeneous and consist of erythema nodosum lesions&#44; pustules&#44; necrotizing ulcers&#44; superficial thrombophlebitis and vasculitis&#44; and lesions similar to those seen in pyoderma gangrenosum or Sweet syndrome&#44; among others&#46; It is associated with positive pathergy reactions&#46; Recurrent mouth ulcers are the first manifestation in a high percentage of patients&#46; They tend to be multiple&#44; painful&#44; and heal without leaving a scar&#44; unlike genital ulcers&#44; which leave characteristic flat scars&#46; Neutrophilic vasculitis and&#47;or thrombosis are characteristic histopathologic findings&#46;</p></span><span id="sec0290" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0310">Associated Clinical Manifestations</span><p id="par0295" class="elsevierStylePara elsevierViewall">Eye involvement is the main cause of morbidity in Beh&#231;et syndrome&#46; The most common condition is posterior uveitis&#44; but anterior uveitis and uveitis with hypopyon are also observed&#46; Patients may also develop arthritis and a large spectrum of manifestations secondary to systemic vasculitis&#44; such as arterial and venous thrombosis&#44; aneurysms&#44; and digestive and neurological symptoms&#46;</p></span></span></span><span id="sec0295" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0315">Ethical Disclosures</span><span id="sec0300" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0320">Protection of humans and animals</span><p id="par0300" class="elsevierStylePara elsevierViewall">The authors declare that no tests were carried out in humans or animals for the purpose of this study&#46;</p></span><span id="sec0305" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0325">Confidentiality of data</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital&#39;s protocol on the publication of data concerning patients&#46;</p></span><span id="sec0310" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0330">Right to privacy and informed consent</span><p id="par0310" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span></span><span id="sec0315" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0335">Conflicts of Interest</span><p id="par0315" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres888166"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec874138"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres888167"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec874137"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Urticaria-like Syndromes"
          "secciones" => array:2 [
            0 => array:3 [
              "identificador" => "sec0015"
              "titulo" => "Cryopyrin-associated Periodic Syndromes"
              "secciones" => array:3 [
                0 => array:3 [
                  "identificador" => "sec0020"
                  "titulo" => "Familial Cold Autoinflammatory Syndrome"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0025"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0030"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                1 => array:3 [
                  "identificador" => "sec0035"
                  "titulo" => "Muckle-Wells syndrome"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0040"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0045"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                2 => array:3 [
                  "identificador" => "sec0050"
                  "titulo" => "Neonatal-onset Multisystem Inflammatory Disease&#47;Chronic Infantile Neurological Cutaneous Articular Syndrome"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0055"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0060"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "sec0065"
              "titulo" => "Hereditary Periodic Fever Syndromes"
              "secciones" => array:6 [
                0 => array:3 [
                  "identificador" => "sec0070"
                  "titulo" => "Familial Mediterranean Fever"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0075"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0080"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                1 => array:3 [
                  "identificador" => "sec0085"
                  "titulo" => "TNF Receptor&#8211;Associated Periodic Syndrome"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0090"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0095"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                2 => array:3 [
                  "identificador" => "sec0100"
                  "titulo" => "Mevalonate Kinase Deficiency&#8211;Hyperimmunoglobulin D Syndrome"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0105"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0110"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                3 => array:2 [
                  "identificador" => "sec0115"
                  "titulo" => "PLCG2-associated Antibody Deficiency and Immune Dysregulation and Autoinflammation PLCG2-associated Antibody Deficiency and Immune Dysregulation"
                ]
                4 => array:3 [
                  "identificador" => "sec0120"
                  "titulo" => "Autoinflammatory Syndrome With Lymphedema"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0125"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0130"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
                5 => array:3 [
                  "identificador" => "sec0135"
                  "titulo" => "NLRP1-associated Autoinflammation With Arthritis and Dyskeratosis"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0140"
                      "titulo" => "Cutaneous Manifestations"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0145"
                      "titulo" => "Associated Clinical Manifestations"
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0150"
          "titulo" => "Pustular Syndromes"
          "secciones" => array:5 [
            0 => array:3 [
              "identificador" => "sec0155"
              "titulo" => "Deficiency of the Interleukin-1-Receptor Antagonist"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0160"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0165"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "sec0170"
              "titulo" => "Deficiency of Interleukin-36-Receptor Antagonist"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0175"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0180"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "sec0185"
              "titulo" => "Pyogenic Sterile Arthritis&#44; Pyoderma Gangrenosum&#44; Acne"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0190"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0195"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "sec0200"
              "titulo" => "Majeed Syndrome"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0205"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0210"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "sec0215"
              "titulo" => "Autoinflammatory Syndrome Associated With Pyrins and Neutrophilic Dermatosis"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0220"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0225"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0230"
          "titulo" => "Syndromes With Mucocutaneous Ulcers"
          "secciones" => array:4 [
            0 => array:3 [
              "identificador" => "sec0235"
              "titulo" => "Periodic Fever Syndrome With Aphthous Stomatitis&#44; Pharyngitis&#44; and Adenitis"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0240"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0245"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "sec0250"
              "titulo" => "Periodic Fever Syndrome&#44; Immunodeficiency&#44; and Thrombocytopenia"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0255"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0260"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "sec0265"
              "titulo" => "Beh&#231;et-like Autoinflammatory Syndrome Associated With A20 Haploinsufficiency"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0270"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0275"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "sec0280"
              "titulo" => "Beh&#231;et Syndrome"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0285"
                  "titulo" => "Cutaneous Manifestations"
                ]
                1 => array:2 [
                  "identificador" => "sec0290"
                  "titulo" => "Associated Clinical Manifestations"
                ]
              ]
            ]
          ]
        ]
        8 => array:3 [
          "identificador" => "sec0295"
          "titulo" => "Ethical Disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0300"
              "titulo" => "Protection of humans and animals"
            ]
            1 => array:2 [
              "identificador" => "sec0305"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0310"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        9 => array:2 [
          "identificador" => "sec0315"
          "titulo" => "Conflicts of Interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-09-01"
    "fechaAceptado" => "2016-12-23"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec874138"
          "palabras" => array:4 [
            0 => "Monogenic autoinflammatory diseases"
            1 => "Skin manifestations"
            2 => "Classification"
            3 => "Histologic diagnosis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec874137"
          "palabras" => array:4 [
            0 => "Enfermedades autoinflamatorias monogen&#233;ticas"
            1 => "Manifestaciones cut&#225;neas"
            2 => "Clasificaci&#243;n"
            3 => "Diagn&#243;stico histol&#243;gico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Monogenic autoinflammatory diseases are a heterogeneous emergent group of conditions that are currently under intensive study&#46; We review the etiopathogenesis of these syndromes and their principal manifestations&#46; Our aim is to propose a classification system based on the clinicopathologic features of typical skin lesions for routine clinical use in dermatology&#46; Our focus is on diagnosis in pediatric practice given that this is the period when the signs and symptoms of these syndromes first appear&#46; In Part 1 we discuss the course of urticaria-like syndromes&#44; which include cryopyrin-associated periodic conditions and hereditary periodic fever syndromes&#46; Pustular syndromes are also covered in this part&#46; Finally&#44; we review the range of therapies available as well as the genetic mutations associated with these autoinflammatory diseases&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las enfermedades monog&#233;nicas autoinflamatorias son un grupo de enfermedades emergentes y heterog&#233;neas en continuo estudio y desarrollo en la actualidad&#46; Nuestro objetivo es revisar estas enfermedades desde el punto de vista de su etiopatogenia y principales manifestaciones&#44; con el fin de proponer una clasificaci&#243;n&#44; basada en las caracter&#237;sticas clinicopatol&#243;gicas de las lesiones cut&#225;neas t&#237;picas&#44; que resulte de utilidad en la pr&#225;ctica cl&#237;nica habitual de los dermat&#243;logos&#46; El texto est&#225; enfocado en el diagn&#243;stico de estos s&#237;ndromes durante la edad pedi&#225;trica&#44; ya que es el periodo habitual de aparici&#243;n de los primeros s&#237;ntomas y signos&#46; La primera parte de la revisi&#243;n se centrar&#225; en el desarrollo de los s&#237;ndromes urticariformes&#44; que incluyen a su vez las criopirinopat&#237;as y los s&#237;ndromes hereditarios asociados a fiebres peri&#243;dicas&#44; y de los s&#237;ndromes pustulosos&#44; resumiendo al final del texto las alternativas terap&#233;uticas de estos s&#237;ndromes autoinflamatorios y sus mutaciones gen&#233;ticas&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Hern&#225;ndez-Ostiz S&#44; Prieto-Torres L&#44; Xirotagaros G&#44; Noguera-Morel L&#44; Hern&#225;ndez-Mart&#237;n &#193;&#44; Torrelo A&#46; Enfermedades autoinflamatorias en dermatolog&#237;a pedi&#225;trica&#46; Parte 1&#58; s&#237;ndromes urticariformes&#44; s&#237;ndromes pustulosos y s&#237;ndromes con ulceraciones cut&#225;neo-mucosas&#46; Actas Dermosifiliogr&#46; 2017&#59;108&#58;609&#8211;619&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2296
            "Ancho" => 3170
            "Tamanyo" => 293033
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">NLRP3 inflammasome&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ASC indicates adaptor protein&#59; CARD&#44; caspase activation and recruitment domain&#59; DAMPS&#44; damage-associated molecular patterns&#59; LRR&#44; leucin-rich repeat&#59; PAMPS&#44; pathogen-associated molecular patterns&#59; PYD&#44; pyrin domain&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 676
            "Ancho" => 975
            "Tamanyo" => 158379
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">NOMID &#40;neonatal-onset multisystem inflammatory disease&#41;&#46; Permanent urticaria-like migratory eruption&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1300
            "Ancho" => 975
            "Tamanyo" => 610096
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">NOMID &#40;neonatal-onset multisystem inflammatory disease&#41;&#46; Mixed perivascular superficial and deep inflammatory infiltrate associated with a neutrophilic infiltrate in the eccrine gland &#40;hematoxylin-eosin&#44; original magnification &#215;20&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1020
            "Ancho" => 975
            "Tamanyo" => 237937
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">DITRA &#40;deficiency of the IL-36 receptor antagonist&#41;&#46; Generalized pustular eruption with polycyclic contours on an erythematous base&#44; similar to an outbreak of generalized pustular psoriasis&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AD&#44; autosomal dominant inheritance&#59; APLAID&#44; autoinflammation PLCG2-associated antibody deficiency and immune dysregulation syndrome&#59; AR&#44; autosomal recessive inheritance&#59; CINCA&#44; chronic infantile neurological cutaneous articular syndrome&#59; DIRA&#44; deficiency of the interleukin-1-receptor antagonist DITRA&#44; deficiency of the IL-36 receptor antagonist&#59; HIDS&#44; hyperimmunoglobulinemia D syndrome&#59; IL&#44; interleukin&#59; FMF&#44; familial Mediterranean fever&#59; MWS&#44; Muckle-Wells syndrome&#59; NOMID&#44; neonatal-onset multisystem inflammatory disease&#59; NSAIDs&#44; nonsteroidal anti-inflammatory drugs&#59; PAPA&#44; pyogenic sterile arthritis&#44; pyoderma gangrenosum&#44; and acne&#59; PFAPA&#44; periodic fever&#44; aphthous stomatitis&#44; pharyngitis&#44; and cervical adenitis&#59; PLAID&#44; PLCG2-associated antibody deficiency and immune dysregulation syndrome&#59; TRAPS&#44; tumor necrosis factor receptor-associated syndrome&#59; TNF&#44; tumor necrosis factor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FMF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">MEFV</span> &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pyrin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Of choice&#58; colchicine<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;anakinra&#44; rilonacept&#44; canakinumab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Interferon-alfa&#44; thalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">7&#44;19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HIDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">MVK</span> &#40;mevalonate kinase&#41; &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mevalonate kinase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Colchicine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSAIDs<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Simvastatin<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">22&#44;23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Thalidomide<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">6&#44;19&#44;20&#44;25&#44;26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">19&#44;27&#44;28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TRAPS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">TNFRSF1A</span> &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF receptor p55 &#40;TNFR1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">19&#44;29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;nonresponse to colchicine&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">19&#44;29&#8211;33</span></a> IL-1 antagonistas<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">7&#44;19&#44;20&#44;25&#44;29&#44;34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-6 antagonists &#40;tocilizumab&#41;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">29&#44;35&#44;36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tacrolimus<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PFAPA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">19&#44;38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cimetidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Colchicine<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tonsillectomy<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PLAID&#47;APLAID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">PLCG2</span> &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Phospholipase C gamma 2 &#40;PLCG2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High doses of systemic corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists &#40;partial response&#41;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">8&#44;9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FCAS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">NLRP3&#47;CIAS1</span> &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cryopyrin &#40;NALP3 or PYPAF1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nonexposure to coldIL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">7&#44;19&#44;20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MWS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">NLRP3&#47;CIAS1</span> &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cryopyrin &#40;NALP3 or PYPAF1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">6&#44;7&#44;19&#44;20&#44;41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NOMID&#47;CINCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">NLRP3</span>&#47;<span class="elsevierStyleItalic">CIAS1</span> &#40;AD&#41;&#59; some sporadic cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cryopyrin &#40;NALP3 or PYPAF1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">3&#44;6&#44;7&#44;19&#44;20&#44;42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DIRA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1RN&#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Interleukin-1 receptor antagonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">11&#44;19&#44;20&#44;25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DITRA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">IL-36RN</span> &#40;AR&#44; sporadic cases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Interleukin-36 receptor antagonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not established<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Acitretin<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical and systemic corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ciclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Granulocyte and monocyte apheresis<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-antagonists<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAPA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">PSTPIP1&#47;CD2BP1</span> &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PSTPIP1&#47;CD2BP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systemic corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">7&#44;19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ciclosporin&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a>thalidomide&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a> dapsone&#44; tacrolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intravenous immunoglobulin<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-antagonists<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">19&#44;25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Combination of isotretinoin and anakinra<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">14&#44;15&#44;19</span></a> &#40;possibly treatment of choice&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Majeed Syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">LPIN2</span> &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Phosphatidate phosphatase LPIN2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Corticosteroids&#44; interferon gamma&#44; bisphosphonates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TNF inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">7&#44;16&#44;17&#44;25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PAAND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">MEFV</span> gene &#40;AD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pyrin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IL-1 antagonists<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">18</span></a> &#40;1 patient with good response&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1501029.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Genetic Mutations and Treatment Alternatives&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:44 [
            0 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoinflammatory diseases&#58; Clinical and genetic advances"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Farasat"
                            1 => "I&#46; Aksentijevich"
                            2 => "J&#46;R&#46; Toro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol"
                        "fecha" => "2008"
                        "volumen" => "144"
                        "paginaInicial" => "392"
                        "paginaFinal" => "402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18347298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoinflammatory syndromes for the dermatologist"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; D&#225;vila-Seijo"
                            1 => "A&#46; Hern&#225;ndez-Mart&#237;n"
                            2 => "A&#46; Torrelo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clindermatol.2014.02.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Dermatol"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "paginaInicial" => "488"
                        "paginaFinal" => "501"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25017460"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic&#44; cutaneous&#44; articular syndrome&#47;neonatal-onset multisystem inflammatory disease&#58; Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;I&#46; Ar&#243;stegui"
                            1 => "M&#46;D&#46; Lopez Salda&#241;a"
                            2 => "M&#46; Pascal"
                            3 => "D&#46; Clemente"
                            4 => "M&#46; Aymerich"
                            5 => "F&#46; Balaguer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.27342"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2010"
                        "volumen" => "62"
                        "paginaInicial" => "1158"
                        "paginaFinal" => "1166"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20131270"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene&#58; Epidemiological study and lessons from eight years of genetic analysis in France"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Cuisset"
                            1 => "I&#46; Jeru"
                            2 => "B&#46; Dumont"
                            3 => "A&#46; Fabre"
                            4 => "E&#46; Cochet"
                            5 => "J&#46; Le Bozec"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2010.138420"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "paginaInicial" => "495"
                        "paginaFinal" => "499"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21109514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cryopyrin-associated periodic syndromes and autoinflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Shinkai"
                            1 => "T&#46; McCalmont"
                            2 => "K&#46; Leslie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2230.2007.02540.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Dermatol"
                        "fecha" => "2008"
                        "volumen" => "33"
                        "paginaInicial" => "1"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17927785"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current status of understanding the pathogenesis and management of patients with NOMID&#47;CINCA"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Goldbach-Mansky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11926-011-0165-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Rheumatol Rep"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "123"
                        "paginaFinal" => "131"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21538043"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monogenic autoinflammatory diseases&#58; Concept and clinical manifestations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;A&#46; De Jesus"
                            1 => "R&#46; Goldbach-Mansky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clim.2013.03.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Immunol"
                        "fecha" => "2013"
                        "volumen" => "147"
                        "paginaInicial" => "155"
                        "paginaFinal" => "174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23711932"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A hypermorphic missense mutation in PLCG2&#44; encoding phospholipase C&#40;2&#44; causes a dominantly inherited autoinflammatory disease with immunodeficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46; Zhou"
                            1 => "G-S&#46; Lee"
                            2 => "J&#46; Brady"
                            3 => "S&#46; Datta"
                            4 => "M&#46; Katan"
                            5 => "A&#46; Sheikh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajhg.2012.08.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2012"
                        "volumen" => "91"
                        "paginaInicial" => "713"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23000145"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monogenic autoinflammatory diseases&#58; Cytokinopathies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Moghaddas"
                            1 => "S&#46;L&#46; Masters"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cyto.2015.02.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cytokine"
                        "fecha" => "2015"
                        "volumen" => "74"
                        "paginaInicial" => "237"
                        "paginaFinal" => "246"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25814341"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Aksentijevich"
                            1 => "S&#46;L&#46; Masters"
                            2 => "P&#46;J&#46; Ferguson"
                            3 => "P&#46; Dancey"
                            4 => "J&#46; Frenkel"
                            5 => "A&#46; van Royen-Kerkhoff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0807865"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "360"
                        "paginaInicial" => "2426"
                        "paginaFinal" => "2437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19494218"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A novel mutation in the interleukin-1 receptor antagonist associated with intrauterine disease onset"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Altiok"
                            1 => "F&#46; Aksoy"
                            2 => "Y&#46; Perk"
                            3 => "F&#46; Taylan"
                            4 => "P&#46;W&#46; Kim"
                            5 => "B&#46; Il&#305;kkan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clim.2012.08.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Immunol"
                        "fecha" => "2012"
                        "volumen" => "145"
                        "paginaInicial" => "77"
                        "paginaFinal" => "81"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22940634"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Marrakchi"
                            1 => "P&#46; Guigue"
                            2 => "B&#46;R&#46; Renshaw"
                            3 => "A&#46; Puel"
                            4 => "X&#46;Y&#46; Pei"
                            5 => "S&#46; Fraitag"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1013068"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2011"
                        "volumen" => "365"
                        "paginaInicial" => "620"
                        "paginaFinal" => "628"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21848462"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brief report&#58; Genotype&#44; phenotype&#44; and clinical course in five patients with PAPA syndrome &#40;pyogenic sterile arthritis&#44; pyoderma gangrenosum&#44; and acne&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;P&#46; Demidowich"
                            1 => "A&#46;F&#46; Freeman"
                            2 => "D&#46;B&#46; Kuhns"
                            3 => "I&#46; Aksentijevich"
                            4 => "J&#46;I&#46; Gallin"
                            5 => "M&#46;L&#46; Turner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.34332"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "2022"
                        "paginaFinal" => "2027"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22161697"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peculiarities of PAPA syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Tallon"
                            1 => "M&#46; Corkill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/kei178"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2006"
                        "volumen" => "45"
                        "paginaInicial" => "1140"
                        "paginaFinal" => "1143"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16527883"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoinflammatory pustular neutrophilic diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46;B&#46; Naik"
                            1 => "E&#46;W&#46; Cowen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.det.2013.04.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Clin"
                        "fecha" => "2013"
                        "volumen" => "31"
                        "paginaInicial" => "405"
                        "paginaFinal" => "425"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23827244"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of anti-IL-1 treatment in Majeed syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Herlin"
                            1 => "B&#46; Fiirgaard"
                            2 => "M&#46; Bjerre"
                            3 => "G&#46; Kerndrup"
                            4 => "H&#46; Hasle"
                            5 => "X&#46; Bing"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2012-201818"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2013"
                        "volumen" => "72"
                        "paginaInicial" => "410"
                        "paginaFinal" => "413"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23087183"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;L&#46; Masters"
                            1 => "V&#46; Lagou"
                            2 => "I&#46; J&#233;ru"
                            3 => "P&#46;J&#46; Baker"
                            4 => "L&#46; Van Eyck"
                            5 => "D&#46;A&#46; Parry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Sci Transl Med"
                        "fecha" => "2016"
                        "volumen" => "8"
                        "paginaInicial" => "332"
                        "paginaFinal" => "345"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46; Zhou"
                            1 => "H&#46; Wang"
                            2 => "D&#46;M&#46; Schwartz"
                            3 => "M&#46; Stoffels"
                            4 => "Y&#46;H&#46; Park"
                            5 => "Y&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng.3459"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "2016"
                        "volumen" => "48"
                        "paginaInicial" => "67"
                        "paginaFinal" => "73"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26642243"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric Rheumatology International Trials Organisation &#40;PRINTO&#41; and the Eurofever&#47;Eurotraps Projects&#46; Treatment of autoinflammatory diseases&#58; Results from the Eurofever Registry and a literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Ter Haar"
                            1 => "H&#46; Lachmann"
                            2 => "S&#46; &#214;zen"
                            3 => "P&#46; Woo"
                            4 => "Y&#46; Uziel"
                            5 => "C&#46; Modesto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2011-201268"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2013"
                        "volumen" => "72"
                        "paginaInicial" => "678"
                        "paginaFinal" => "685"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22753383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL-1 blockade in autoinflammatory syndromes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Goldbach-Mansky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev-med-061512-150641"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Med"
                        "fecha" => "2014"
                        "volumen" => "65"
                        "paginaInicial" => "223"
                        "paginaFinal" => "244"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24422572"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-steroidal anti-inflammatory drugs in the treatment of hyper-IgD syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46; Picco"
                            1 => "M&#46; Gattorno"
                            2 => "M&#46; Di Rocco"
                            3 => "A&#46; Buoncompagni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2001"
                        "volumen" => "60"
                        "paginaInicial" => "904"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11534513"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Simon"
                            1 => "E&#46; Drewe"
                            2 => "J&#46;W&#46; van der Meer"
                            3 => "R&#46;J&#46; Powell"
                            4 => "R&#46;I&#46; Kelley"
                            5 => "A&#46;F&#46;H&#46; Stalenhoef"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clpt.2004.01.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Pharmacol Ther"
                        "fecha" => "2004"
                        "volumen" => "75"
                        "paginaInicial" => "476"
                        "paginaFinal" => "483"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15116060"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A patient with hyper-IgD syndrome responding to simvastatin treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46; Attout"
                            1 => "S&#46; Guez"
                            2 => "I&#46; Ranaivo"
                            3 => "N&#46; Jameerbaccus"
                            4 => "C&#46; Series"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Intern Med"
                        "fecha" => "2008"
                        "volumen" => "19"
                        "paginaInicial" => "82"
                        "paginaFinal" => "83"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper-IgD and periodic fever syndrome&#58; A randomized&#44; double-blind&#44; placebo controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;P&#46;H&#46; Drenth"
                            1 => "A&#46;G&#46; Vonk"
                            2 => "A&#46; Simon"
                            3 => "R&#46; Powell"
                            4 => "J&#46;W&#46;M&#46; van der Meer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pharmacol Exp Ther"
                        "fecha" => "2001"
                        "volumen" => "298"
                        "paginaInicial" => "1221"
                        "paginaFinal" => "1226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11504824"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treating inflammation by blocking interleukin-1 in humans"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;A&#46; Dinarello"
                            1 => "J&#46;W&#46; van der Meer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Semin Immunol"
                        "fecha" => "2013"
                        "volumen" => "25"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "On-demand anakinra treatment is effective in mevalonate kinase deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46;J&#46; Bodar"
                            1 => "L&#46;M&#46; Kuijk"
                            2 => "J&#46;P&#46; Drenth"
                            3 => "J&#46;W&#46; van der Meer"
                            4 => "A&#46; Simon"
                            5 => "J&#46; Frenkel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2011.149922"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "paginaInicial" => "2155"
                        "paginaFinal" => "2158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21859689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A patient with hyper-IgD syndrome responding to anti-TNF treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Demirkaya"
                            1 => "M&#46;K&#46; Caglar"
                            2 => "H&#46;R&#46; Waterham"
                            3 => "R&#46; Topaloglu"
                            4 => "S&#46; Ozen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-006-0501-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2007"
                        "volumen" => "26"
                        "paginaInicial" => "1757"
                        "paginaFinal" => "1759"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17171314"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hyperimmunoglobulinemia D and periodic fever syndrome&#59; treatment with etanercept and follow-up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Topalo&#287;lu"
                            1 => "N&#46;A&#46; Ayaz"
                            2 => "H&#46;R&#46; Waterham"
                            3 => "A&#46; Y&#252;ce"
                            4 => "F&#46; Gumruk"
                            5 => "O&#46; Sanal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-008-0911-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "27"
                        "paginaInicial" => "1317"
                        "paginaFinal" => "1320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18506569"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#91;Progress in classification and treatment for TNF receptor-associated periodic syndrome&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46; Tsukamoto"
                            1 => "N&#46; Ueda"
                            2 => "T&#46; Horiuchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nihon Rinsho Meneki Gakkai Kaishi"
                        "fecha" => "2010"
                        "volumen" => "34"
                        "paginaInicial" => "361"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22041423"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Successful treatment with infliximab of a patient with tumor necrosis factor-associated periodic syndrome &#40;TRAPS&#41; who failed to respond to etanercept"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Krelenbaum"
                            1 => "A&#46; Chaiton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.091094"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2010"
                        "volumen" => "37"
                        "paginaInicial" => "1780"
                        "paginaFinal" => "1782"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20675856"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of etanercept in the treatment of tumor necrosis factor receptor-associated periodic syndrome&#58; Personal experience and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Cantarini"
                            1 => "D&#46; Rigante"
                            2 => "O&#46;M&#46; Lucherini"
                            3 => "R&#46; Cimaz"
                            4 => "F&#46; Laghi Pasini"
                            5 => "C&#46;T&#46; Baldari"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/039463201002300303"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Immunopathol Pharmacol"
                        "fecha" => "2010"
                        "volumen" => "23"
                        "paginaInicial" => "701"
                        "paginaFinal" => "707"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20943039"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lessons from anti-TNF biologics&#58; infliximab failure in a TRAPS family with the T50<span class="elsevierStyleHsp" style=""></span>M mutation in TNFRSF1A"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Nedjai"
                            1 => "N&#46; Quillinan"
                            2 => "R&#46;J&#46; Coughlan"
                            3 => "L&#46; Church"
                            4 => "M&#46;F&#46; McDermott"
                            5 => "G&#46;A&#46; Hitman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/978-1-4419-6612-4_43"
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Exp Med Biol"
                        "fecha" => "2011"
                        "volumen" => "691"
                        "paginaInicial" => "409"
                        "paginaFinal" => "419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21153346"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Failure of sustained response to etanercept and refractoriness to anakinra in patients with T50<span class="elsevierStyleHsp" style=""></span>M TNF-receptor-associated periodic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Quillinan"
                            1 => "G&#46; Mannion"
                            2 => "A&#46; Mohammad"
                            3 => "R&#46; Coughlan"
                            4 => "L&#46;J&#46; Dickie"
                            5 => "M&#46;F&#46; McDermott"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2010.144279"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2011"
                        "volumen" => "70"
                        "paginaInicial" => "1692"
                        "paginaFinal" => "1693"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21378401"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS&#58; Dramatic response to Anakinra"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Cattalini"
                            1 => "A&#46; Meini"
                            2 => "P&#46; Monari"
                            3 => "G&#46; Gualdi"
                            4 => "M&#46; Arisi"
                            5 => "F&#46; Pelucchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatol Online J"
                        "fecha" => "2013"
                        "volumen" => "19"
                        "paginaInicial" => "20405"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24314780"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of interleukin-6 in a patient with tumor necrosis factor receptor-associated periodic syndrome&#58; Assessment of outcomes following treatment with the anti-interleukin-6 receptor monoclonal antibody tocilizumab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;M&#46; Vaitla"
                            1 => "P&#46;M&#46; Radford"
                            2 => "P&#46;J&#46; Tighe"
                            3 => "R&#46;J&#46; Powell"
                            4 => "E&#46;M&#46; McDermott"
                            5 => "I&#46; Todd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.30215"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "paginaInicial" => "1151"
                        "paginaFinal" => "1155"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21225679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A case presenting with the clinical characteristics of tumor necrosis factor &#40;TNF&#41; receptor-associated periodic syndrome &#40;TRAPS&#41; without TNFRSF1A mutations successfully treated with tocilizumab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Hosoya"
                            1 => "F&#46; Mizoguchi"
                            2 => "H&#46; Hasegawa"
                            3 => "K&#46; Miura"
                            4 => "R&#46; Koike"
                            5 => "T&#46; Kubota"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2169/internalmedicine.54.3371"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intern Med"
                        "fecha" => "2015"
                        "volumen" => "54"
                        "paginaInicial" => "2069"
                        "paginaFinal" => "2072"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26278305"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Succesful treatment using tacrolimus &#40;FK506&#41; in a patient with TNF receptor-associated periodic syndrome &#40;TRAPS&#41; complicated with monocytic fasciitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46; Ida"
                            1 => "T&#46; Aramaki"
                            2 => "K&#46; Arima"
                            3 => "T&#46; Origuchi"
                            4 => "A&#46; Kawakami"
                            5 => "K&#46; Eguchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/kel178"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2006"
                        "volumen" => "45"
                        "paginaInicial" => "1171"
                        "paginaFinal" => "1173"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16801330"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Documento de Consenso de la Sociedad de Infectolog&#237;a Pedi&#225;trica y la Sociedad de Reumatolog&#237;a Pedi&#225;trica sobre el diagn&#243;stico diferencial y el abordaje terap&#233;utico de la fiebre recurrente"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Calvo Rey"
                            1 => "P&#46; Soler-Palac&#237;n"
                            2 => "R&#46; Merino Mu&#241;oz"
                            3 => "J&#46; Saavedra Lozano"
                            4 => "J&#46; Ant&#243;n L&#243;pez"
                            5 => "J&#46;L&#46; Ar&#243;stegui"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "An Pediatr &#40;Barc&#41;"
                        "fecha" => "2011"
                        "volumen" => "74"
                        "paginaInicial" => "194e1"
                        "paginaFinal" => "194e16"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Colchicine prophylaxis for frequent periodic fever&#44; aphthous stomatitis&#44; pharyngitis and adenitis episodes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Tasher"
                            1 => "M&#46; Stein"
                            2 => "I&#46; Dalal"
                            3 => "E&#46; Somekh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1651-2227.2008.00837.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2008"
                        "volumen" => "97"
                        "paginaInicial" => "1090"
                        "paginaFinal" => "1092"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18462461"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effectiveness of adenotonsillectomy in PFAPA syndrome&#58; A randomized study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "W&#46; Garavello"
                            1 => "M&#46; Romagnoli"
                            2 => "R&#46;M&#46; Gaini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jpeds.2009.02.038"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "2009"
                        "volumen" => "155"
                        "paginaInicial" => "250"
                        "paginaFinal" => "253"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19464029"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The STING pathway and regulation of innate immune signaling in response to DNA pathogens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Ishikawa"
                            1 => "G&#46;N&#46; Barber"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00018-010-0605-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Mol Life Sci"
                        "fecha" => "2011"
                        "volumen" => "68"
                        "paginaInicial" => "1157"
                        "paginaFinal" => "1165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21161320"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46;N&#46; Hawkins"
                            1 => "H&#46;J&#46; Lachmann"
                            2 => "E&#46; Aganna"
                            3 => "M&#46;F&#46; McDermott"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.20033"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2004"
                        "volumen" => "50"
                        "paginaInicial" => "607"
                        "paginaFinal" => "612"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14872505"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A case of old age-onset generalized pustular psoriasis with a deficiency of IL-36RN &#40;DITRA&#41; treated by granulocyte and monocyte apheresis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Tominaga"
                            1 => "M&#46; Yamamoto"
                            2 => "Y&#46; Imai"
                            3 => "K&#46; Yamanishi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000380876"
                      "Revista" => array:6 [
                        "tituloSerie" => "Case Rep Dermatol"
                        "fecha" => "2015"
                        "volumen" => "7"
                        "paginaInicial" => "29"
                        "paginaFinal" => "35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25848350"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Rossi-Semerano"
                            1 => "M&#46; Piram"
                            2 => "C&#46; Chiaverini"
                            3 => "D&#46; de Ricaud"
                            4 => "A&#46; Smahi"
                            5 => "I&#46; Kon&#233;-Paut"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2013"
                        "volumen" => "132"
                        "paginaInicial" => "1043"
                        "paginaFinal" => "1047"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/15782190/0000010800000007/v2_201708291348/S1578219017302111/v2_201708291348/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "6177"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Reviews"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010800000007/v2_201708291348/S1578219017302111/v2_201708291348/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219017302111?idApp=UINPBA000044"
]

Información del artículo

ISSN: 15782190
Idioma original: Inglés

DOI:10.1016/j.adengl.2017.06.015

Datos actualizados diariamente

año/Mes	Html	Pdf	Total

2024 Noviembre	26	10	36
2024 Octubre	136	39	175
2024 Septiembre	142	25	167
2024 Agosto	162	52	214
2024 Julio	141	39	180
2024 Junio	153	61	214
2024 Mayo	146	57	203
2024 Abril	117	45	162
2024 Marzo	131	29	160
2024 Febrero	115	38	153
2024 Enero	109	40	149
2023 Diciembre	99	29	128
2023 Noviembre	128	34	162
2023 Octubre	116	44	160
2023 Septiembre	97	46	143
2023 Agosto	88	19	107
2023 Julio	134	38	172
2023 Junio	102	32	134
2023 Mayo	150	28	178
2023 Abril	134	23	157
2023 Marzo	175	36	211
2023 Febrero	135	40	175
2023 Enero	110	54	164
2022 Diciembre	85	48	133
2022 Noviembre	69	28	97
2022 Octubre	58	22	80
2022 Septiembre	37	44	81
2022 Agosto	43	45	88
2022 Julio	38	49	87
2022 Junio	36	23	59
2022 Mayo	73	49	122
2022 Abril	90	65	155
2022 Marzo	89	71	160
2022 Febrero	84	50	134
2022 Enero	93	66	159
2021 Diciembre	56	69	125
2021 Noviembre	59	57	116
2021 Octubre	104	74	178
2021 Septiembre	325	64	389
2021 Agosto	58	55	113
2021 Julio	63	49	112
2021 Junio	86	48	134
2021 Mayo	219	79	298
2021 Abril	178	100	278
2021 Marzo	130	64	194
2021 Febrero	113	47	160
2021 Enero	80	68	148
2020 Diciembre	115	54	169
2020 Noviembre	51	40	91
2020 Octubre	50	28	78
2020 Septiembre	65	26	91
2020 Agosto	47	42	89
2020 Julio	50	24	74
2020 Junio	45	38	83
2020 Mayo	41	22	63
2020 Abril	25	16	41
2020 Marzo	30	22	52
2020 Febrero	3	2	5
2019 Diciembre	4	0	4
2019 Octubre	1	0	1
2019 Septiembre	5	0	5
2019 Agosto	2	0	2
2019 Junio	2	0	2
2019 Mayo	2	1	3
2019 Abril	3	0	3
2019 Marzo	3	0	3
2019 Febrero	8	0	8
2019 Enero	1	0	1
2018 Diciembre	6	0	6
2018 Noviembre	1	0	1
2018 Octubre	6	0	6
2018 Septiembre	5	0	5
2018 Julio	1	0	1
2018 Mayo	0	1	1
2018 Febrero	37	9	46
2018 Enero	58	12	70
2017 Diciembre	72	19	91
2017 Noviembre	55	14	69
2017 Octubre	57	26	83
2017 Septiembre	318	50	368
2017 Agosto	110	44	154
2017 Julio	7	29	36

Mostrar todo

Indexada en:

Síguenos:

Estadísticas

Indexada en:

Síguenos:

Estadísticas

Suscríbase a la newsletter