Case Report
Erythema Nodosum Leprosum and Reversal Reaction in 2 Cases of Imported Leprosy
Eritema nudoso leproso y reacción de reversión en 2 casos de lepra importada
A. Pulido-Pérez
, M.D. Mendoza-Cembranos, J.A. Avilés-Izquierdo, R. Suárez-Fernández
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Servicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Pulido-Pérez, M.D. Mendoza-Cembranos, J.A. Avilés-Izquierdo, R. Suárez-Fernández" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Pulido-Pérez" "email" => array:1 [ 0 => "ana.pulido@madrimasd.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.D." "apellidos" => "Mendoza-Cembranos" ] 2 => array:2 [ "nombre" => "J.A." "apellidos" => "Avilés-Izquierdo" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Suárez-Fernández" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eritema nudoso leproso y reacción de reversión en 2 casos de lepra importada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 669 "Ancho" => 900 "Tamanyo" => 257951 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Lymphocytic, neutrophilic, and histiocytic infiltrate in the deep dermis in a patient with erythema nodosum leprosum (hematoxylin-eosin, original magnification ×40).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hansen disease, or leprosy, is uncommon in Spain. It is no longer considered a public health problem in our country<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> and most new cases are imported from leprosy-endemic areas in Southeast Asia, South America, and Africa.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The virtual absence of autochthonous cases and the added difficulty of evaluating dermatological conditions in patients from other racial groups complicate the early diagnosis of leprosy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Leprosy is characterized by a wide spectrum of clinical manifestations that affect the skin, the mucosas, the eyes, the organs, and/or the nerves. On occasions, its cardinal signs or symptoms may be masked by sudden clinical changes known as leprosy reactions,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which are triggered by changes in immune response.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Multiple factors are involved in the development of leprosy reactions, but commencement of specific leprosy treatment is a factor in a considerable number of cases.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We describe 2 cases of type 1 and type 2 leprosy reactions in patients with previously undiagnosed leprosy that illustrate the diagnostic challenges in such cases.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><p id="par0020" class="elsevierStylePara elsevierViewall">The first patient, a 25-year-old woman from Brazil who had been living in Spain for 6 months, visited the emergency department with high fever (up to 39<span class="elsevierStyleHsp" style=""></span>°C), general malaise, watery rhinorrhea, and painful, erythematous nodules located predominantly on the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The manifestations had started the previous week, but the patient had experienced similar lesions—which cleared spontaneously—on several occasions in the previous 3 months. Blood tests revealed a normocytic, normochromic anemia, leukocytosis with neutrophilia, mild elevation of the tranaminases, and considerably increased serum levels of immunoglobulin G. The ear, nose, and throat examination confirmed mucosal edema in the paranasal sinuses. The skin examination revealed multiple, asymptomatic brownish papules symmetrically distributed on the legs and the arches of the soles that were clinically diagnosed as lepromas. There were also purple nonulcerated papules on the distal third of the toes (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The path of the right common peroneal nerve was thickened and electromyography demonstrated a severe sensory-motor neuropathy. Biopsy of a nodule showed a diffuse inflammatory infiltrate in the deep dermis and subcutaneous tissue composed of lymphocytes, neutrophils and histiocytes with vacuolated cytoplasm (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The neutrophils exhibited marked tropism for the walls of the small dermal vessels but there was no evidence of fibrinoid necrosis. Ziehl-Neelsen staining showed acid-alcohol-fast bacilli (AAFB) within the histiocytes. A slit-skin smear taken from the earlobe, elbow, and a brownish papule on the leg showed 10 AAFB in one 100× microscope field (bacterial index, 3+). The diagnosis was erythema nodosum leprosum in a patient with subpolar lepromatous leprosy. Multiple drug therapy (MDT) was initiated following the regimen recommended by the World Health Organization for patients with multibacillary leprosy (rifampicin, clofazimine, and dapsone) in combination with oral corticosteroids (prednisone, 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d). The nodules, fever, and general malaise all resolved. However, when the corticosteroid dose was reduced to 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d, the patient experienced a new episode of nodules and fever that required treatment with thalidomide (150<span class="elsevierStyleHsp" style=""></span>mg/d). The response was complete.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The second patient was a 38-year-old man, born in the Philippine Islands and resident in Spain for 4 months, who visited the emergency department following the sudden worsening of annular skin lesions that had developed initially on the face and been treated in the patient's country of origin a year earlier. There was no fever or other systemic symptoms. The patient was questioned further but could not remember what treatment he had received or for how long. Physical examination showed erythematous, edematous plaques that were neither painful nor hot and were located on the lesions initially described by the patient (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). There was also a striking alteration of the nasal pyramid due to a road traffic accident. The neurological examination revealed moderate hypoesthesia in the area of a scaly plaque on the right leg. Two biopsies were taken: one from an erythematous, edematous plaque on the face and the other from the scaly plaque on the right leg. Multiple noncaseating granulomas surrounded by a crown of lymphocytes and located mainly around the nerves and the skin appendages were visible in both lesions, together with edema of the superficial and deep dermis. Skin-smear examination of a facial plaque showed a low bacillary load (2+) of AAFB. The diagnosis was a type 1 reaction in a patient with borderline leprosy. We initiated treatment with corticosteroids (prednisone, 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d), which led to a gradual improvement, plus MDT (rifampicin, clofazimine, and dapsone) for 12 months in view of the little information available on previous treatments.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">Leprosy reactions are sudden changes in the clinical condition of patients diagnosed with leprosy.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They typically occur in patients with immunologically unstable forms of leprosy, but no clinical predictors have been identified to date. These clinical conditions, which are defined according to the Ridley-Jopling classification,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> fall within the spectrum of clinical, microbiologic, histologic, and immunologic manifestations that occur between the 2 extremes, or poles, of leprosy: at one end, tuberculoid or paucibacillary leprosy and at the other, lepromatous or multibacillary leprosy (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The factors involved in the development of these states disrupt the balance between the mycobacteria and the host's immune system. Examples of triggers that alter the immune state are adrenal gland insufficiency, stress, intercurrent infections, pregnancy, and, in particular, specific leprosy treatment.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Classically, there are 2 types of type 1 leprosy reactions: an upgrading, or reversal, reaction and a downgrading reaction.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Downgrading reactions are assumed to represent a shift towards the lepromatous (multibacillary) pole of the disease and are correlated with a decrease in cellular immune response. Reversal reactions, by contrast, are seen in patients who have received treatment and experience an increase in immune response. Type 1 reversal reactions are considered to be a delayed hypersensitivity reaction (or type IV reaction according to the Gell and Coombs classification), involving augmented type 1 helper T-cell response.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Clinically, pre-existing lesions become inflamed and there is considerable exacerbation of neurological manifestations (polyneuritis with marked inflammation of the nerves). Patients may sometimes develop new lesions and general malaise, usually due to the sudden neurological deterioration. Treatment includes rest and systemic corticosteroids.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Type 2 leprosy reactions are essentially due to a type III hypersensitivity reaction, mediated by circulating immune complexes formed by antibodies binding to antigens. These complexes cannot be cleared by the kidneys or phagocytized by macrophages and therefore deposit on the vessel walls.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The release of inflammatory cytokines and the subsequent recruitment of neutrophils contribute to the development of characteristic clinical manifestations that vary according to the organ involved. When the skin is affected patients develop painful inflammatory nodules (a condition known as erythema nodosum leprosum as it is not an inflammatory process occurring within the septa of the subcutaneous tissue), necrotic areas (Lucio phenomenon), or plaques resembling erythema multiforme. Patients may also develop neuritis, with palpable, painful enlargement of the affected nerves.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Treatment includes rest, acetylsalicylic acid, pentoxifylline, systemic corticosteroids, and clofazimine. However, thalidomide (100-300<span class="elsevierStyleHsp" style=""></span>mg/d) remains the treatment of choice in recurrent cases because it is well tolerated and maintains prolonged remission.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> Women of childbearing age receiving this drug must be warned to use effective contraception.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Early diagnosis of leprosy reactions is very important. While these reactions are uncommon in our setting, a late diagnosis can lead to irreversible nerve damage and severe functional impairment.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical Disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of humans and animals</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that no tests were carried out in humans or animals for the purpose of this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of Interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres295317" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec279238" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres295316" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec279237" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of humans and animals" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-12-08" "fechaAceptado" => "2012-09-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec279238" "palabras" => array:5 [ 0 => "Leprosy" 1 => "Hansen disease" 2 => "Vasculitis" 3 => "Thalidomide" 4 => "Neuropathy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec279237" "palabras" => array:5 [ 0 => "Lepra" 1 => "Enfermedad de Hansen" 2 => "Vasculitis" 3 => "Talidomida" 4 => "Neuropatía" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Leprosy reactions, which are abrupt changes in the clinical condition of patients with immunologically unstable forms of the disease, can mask the cardinal signs of leprosy, delaying both diagnosis and treatment. The main complications that arise from delayed diagnosis reflect the characteristic features of the disease, involving impaired nerve function and both local (ulcers, pyogenic infection, osteomyelitis) and systemic compromise. Thorough clinical examination, sensory testing, and, where necessary, histopathology and microbiology, are essential when leprosy is suspected. Rapid initiation of anti-inflammatory treatment reduces the risk of functional impairment, the main concern in leprosy. We describe type 1 and type 2 leprosy reactions in 2 patients who had not yet been diagnosed with the disease.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las leprorreacciones suponen cambios clínicos de inicio súbito en los pacientes que presentan formas inmunológicamente inestables de la enfermedad de Hansen. Estos cuadros pueden enmascarar los signos cardinales de la misma y demorar así su diagnóstico y tratamiento. Las principales complicaciones derivadas de este retraso son las relacionadas con el compromiso neural, local (ulceraciones, piodermitis, osteomielitis…) y/o sistémico característico de estos cuadros. Ante su sospecha debe realizarse un minucioso examen clínico, exploración de la sensibilidad y, cuando se precise, estudio histopatológico y microbiológico. La instauración inmediata de tratamiento antiinflamatorio disminuye el riesgo de secuelas funcionales, principal causa de morbilidad en la lepra. A continuación, se presentan dos casos de leprorreacciones de tipo I y II en pacientes no diagnosticados hasta ese momento de enfermedad de Hansen.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pulido-Pérez A, Mendoza-Cembranos MD, Avilés-Izquierdo JA, Suárez-Fernández R. Eritema nudoso leproso y reacción de reversión en 2 casos de lepra importada. Actas Dermosifiliogr. 2013;104:915–919.</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" => 796 "Ancho" => 900 "Tamanyo" => 100000 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Erythematous nodules affecting both thighs of a patient with erythema nodosum leprosum (type 2 leprosy reaction).</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" => 860 "Ancho" => 900 "Tamanyo" => 112305 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Distal purpuric lesions in a patient with erythema nodosum leprosum (type 2 leprosy reaction).</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" => 669 "Ancho" => 900 "Tamanyo" => 257951 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Lymphocytic, neutrophilic, and histiocytic infiltrate in the deep dermis in a patient with erythema nodosum leprosum (hematoxylin-eosin, original magnification ×40).</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" => 933 "Ancho" => 900 "Tamanyo" => 156609 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Erythematous, edematous facial plaques in a patient with a type 1 leprosy reaction.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: BB, mid-borderline leprosy; BL, borderline lepromatous leprosy; LL<span class="elsevierStyleInf">s</span>, subpolar lepromatous leprosy; NSAIDs, nonsteroidal anti-inflammatory drugs; TT<span class="elsevierStyleInf">s</span>, subpolar tuberculoid leprosy.</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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Type 1 Reactions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Type 2 Reactions \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immune response \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 1 helper cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 2 helper cells \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pathogenesis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type IV (delayed cell-mediated) hypersensitivity reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type III hypersensitivity reaction (immune complex formation and deposition) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical subtypes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TT<span class="elsevierStyleInf">S</span>, BT, BB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BL, LL<span class="elsevierStyleInf">S</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Host \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment (except in downgrading reactions) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatment or not \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Types \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reversal reactionDowngrading reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema nodosum leprosumLucio phenomenonErythema multiforme-like reaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cutaneous manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Edema of previous lesionsIncrease in distal scalingNerve involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NodulesNecrotic areasPolymorphous erythematous plaquesNerve involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Histopathology (changes with respect to conventional histologic findings) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tuberculoid granulomasDermal edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neutrophilic infiltrate in the mid and deep dermis and subcutaneous cellular tissueLeukocytoclastic vasculitis of the small and medium vessels \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RestNSAIDsSystemic corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RestAcetylsalicylic acid, pentoxifyllineSystemic corticosteroidsClofazimineThalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab430520.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Type 1 and 2 Leprosy<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–17</span></a> Reactions.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Historia de la lepra en España" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.T. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 13 | 13 | 26 |
| 2024 Octubre | 142 | 179 | 321 |
| 2024 Septiembre | 175 | 42 | 217 |
| 2024 Agosto | 221 | 71 | 292 |
| 2024 Julio | 200 | 54 | 254 |
| 2024 Junio | 176 | 45 | 221 |
| 2024 Mayo | 206 | 50 | 256 |
| 2024 Abril | 161 | 47 | 208 |
| 2024 Marzo | 204 | 33 | 237 |
| 2024 Febrero | 185 | 38 | 223 |
| 2024 Enero | 124 | 44 | 168 |
| 2023 Diciembre | 149 | 35 | 184 |
| 2023 Noviembre | 170 | 44 | 214 |
| 2023 Octubre | 121 | 40 | 161 |
| 2023 Septiembre | 122 | 43 | 165 |
| 2023 Agosto | 116 | 70 | 186 |
| 2023 Julio | 128 | 106 | 234 |
| 2023 Junio | 146 | 44 | 190 |
| 2023 Mayo | 188 | 56 | 244 |
| 2023 Abril | 174 | 46 | 220 |
| 2023 Marzo | 170 | 38 | 208 |
| 2023 Febrero | 177 | 40 | 217 |
| 2023 Enero | 149 | 45 | 194 |
| 2022 Diciembre | 132 | 32 | 164 |
| 2022 Noviembre | 112 | 45 | 157 |
| 2022 Octubre | 89 | 56 | 145 |
| 2022 Septiembre | 69 | 54 | 123 |
| 2022 Agosto | 49 | 51 | 100 |
| 2022 Julio | 78 | 49 | 127 |
| 2022 Junio | 65 | 28 | 93 |
| 2022 Mayo | 177 | 69 | 246 |
| 2022 Abril | 207 | 87 | 294 |
| 2022 Marzo | 172 | 87 | 259 |
| 2022 Febrero | 158 | 70 | 228 |
| 2022 Enero | 193 | 100 | 293 |
| 2021 Diciembre | 151 | 90 | 241 |
| 2021 Noviembre | 132 | 68 | 200 |
| 2021 Octubre | 178 | 85 | 263 |
| 2021 Septiembre | 136 | 58 | 194 |
| 2021 Agosto | 128 | 50 | 178 |
| 2021 Julio | 183 | 82 | 265 |
| 2021 Junio | 182 | 64 | 246 |
| 2021 Mayo | 175 | 55 | 230 |
| 2021 Abril | 397 | 61 | 458 |
| 2021 Marzo | 186 | 50 | 236 |
| 2021 Febrero | 144 | 35 | 179 |
| 2021 Enero | 106 | 45 | 151 |
| 2020 Diciembre | 87 | 28 | 115 |
| 2020 Noviembre | 73 | 22 | 95 |
| 2020 Octubre | 79 | 25 | 104 |
| 2020 Septiembre | 65 | 17 | 82 |
| 2020 Agosto | 53 | 26 | 79 |
| 2020 Julio | 54 | 19 | 73 |
| 2020 Junio | 57 | 30 | 87 |
| 2020 Mayo | 55 | 35 | 90 |
| 2020 Abril | 36 | 23 | 59 |
| 2020 Marzo | 24 | 22 | 46 |
| 2020 Febrero | 6 | 8 | 14 |
| 2020 Enero | 0 | 7 | 7 |
| 2019 Diciembre | 0 | 8 | 8 |
| 2019 Noviembre | 0 | 5 | 5 |
| 2019 Octubre | 0 | 6 | 6 |
| 2019 Septiembre | 0 | 10 | 10 |
| 2019 Agosto | 0 | 8 | 8 |
| 2019 Julio | 0 | 15 | 15 |
| 2019 Junio | 0 | 20 | 20 |
| 2019 Mayo | 1 | 35 | 36 |
| 2019 Abril | 0 | 66 | 66 |
| 2019 Marzo | 0 | 11 | 11 |
| 2019 Febrero | 1 | 9 | 10 |
| 2019 Enero | 5 | 7 | 12 |
| 2018 Diciembre | 0 | 9 | 9 |
| 2018 Noviembre | 3 | 7 | 10 |
| 2018 Octubre | 4 | 0 | 4 |
| 2018 Septiembre | 9 | 2 | 11 |
| 2018 Agosto | 0 | 15 | 15 |
| 2018 Julio | 0 | 17 | 17 |
| 2018 Junio | 0 | 26 | 26 |
| 2018 Mayo | 0 | 9 | 9 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Marzo | 4 | 3 | 7 |
| 2018 Febrero | 141 | 25 | 166 |
| 2018 Enero | 134 | 25 | 159 |
| 2017 Diciembre | 162 | 27 | 189 |
| 2017 Noviembre | 120 | 21 | 141 |
| 2017 Octubre | 89 | 17 | 106 |
| 2017 Septiembre | 95 | 19 | 114 |
| 2017 Agosto | 133 | 27 | 160 |
| 2017 Julio | 120 | 17 | 137 |
| 2017 Junio | 147 | 50 | 197 |
| 2017 Mayo | 129 | 31 | 160 |
| 2017 Abril | 107 | 24 | 131 |
| 2017 Marzo | 92 | 25 | 117 |
| 2017 Febrero | 95 | 24 | 119 |
| 2017 Enero | 81 | 18 | 99 |
| 2016 Diciembre | 107 | 13 | 120 |
| 2016 Noviembre | 176 | 22 | 198 |
| 2016 Octubre | 215 | 22 | 237 |
| 2016 Septiembre | 300 | 26 | 326 |
| 2016 Agosto | 262 | 25 | 287 |
| 2016 Julio | 113 | 18 | 131 |
| 2016 Junio | 9 | 15 | 24 |
| 2016 Mayo | 7 | 20 | 27 |
| 2016 Abril | 3 | 2 | 5 |
| 2016 Marzo | 10 | 14 | 24 |
| 2016 Febrero | 15 | 22 | 37 |
| 2016 Enero | 7 | 1 | 8 |
| 2015 Diciembre | 5 | 14 | 19 |
| 2015 Noviembre | 9 | 2 | 11 |
| 2015 Octubre | 6 | 29 | 35 |
| 2015 Septiembre | 7 | 2 | 9 |
| 2015 Agosto | 5 | 2 | 7 |
| 2015 Julio | 144 | 13 | 157 |
| 2015 Junio | 91 | 12 | 103 |
| 2015 Mayo | 76 | 27 | 103 |
| 2015 Abril | 56 | 12 | 68 |
| 2015 Marzo | 113 | 16 | 129 |
| 2015 Febrero | 118 | 14 | 132 |
| 2015 Enero | 71 | 11 | 82 |
| 2014 Diciembre | 60 | 27 | 87 |
| 2014 Noviembre | 71 | 4 | 75 |
| 2014 Octubre | 69 | 7 | 76 |
| 2014 Septiembre | 44 | 8 | 52 |
| 2014 Agosto | 49 | 13 | 62 |
| 2014 Julio | 77 | 17 | 94 |
| 2014 Junio | 73 | 17 | 90 |
| 2014 Mayo | 61 | 16 | 77 |
| 2014 Abril | 48 | 9 | 57 |
| 2014 Marzo | 73 | 15 | 88 |
| 2014 Febrero | 51 | 8 | 59 |
| 2014 Enero | 98 | 8 | 106 |
| 2013 Diciembre | 34 | 15 | 49 |
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