Syphilis Maligna: A Presentation to Bear in Mind

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Fustà-Novell, D. Morgado-Carrasco, A. Barreiro-Capurro, C. Manzardo, M. Alsina-Gibert" "autores" => array:6 [ 0 => array:3 [ "nombre" => "X." "apellidos" => "Fustà-Novell" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Barreiro-Capurro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Manzardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:4 [ "nombre" => "M." "apellidos" => "Alsina-Gibert" "email" => array:1 [ 0 => "malsina@clinic.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 5 => array:2 [ "colaborador" => "Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona" "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Enfermedades Infecciosas, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Microbiología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] 1 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sífilis maligna, una presentación de sífilis a tener en cuenta" ] ] "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" => 1085 "Ancho" => 1095 "Tamanyo" => 145985 ] ] ] ] "textoCompleto" => "IntroductionMalignant syphilis (MS) is an uncommon form of secondary syphilis that presents with ulcerated and necrotic skin lesions. The last 2 decades have seen an increase in the number of published cases, mainly in patients with human immunodeficiency virus (HIV).<a class="elsevierStyleCrossRefs" href="#bib0075">1–4</a> Literature on MS is scarce, and is limited mainly to isolated case reports. It is therefore difficult to determine its frequency, pathogenesis, and clinical spectrum. Here we describe the clinical and histological characteristics and treatment response of MS cases diagnosed in our hospital.Material and MethodsWe performed a retrospective observational study of patients diagnosed with syphilis in our hospital during the period 2012 to 2016. We selected patients who had ulcerated, necrotic skin lesions compatible with MS and fulfilled the criteria of Fisher et al<a class="elsevierStyleCrossRef" href="#bib0095">5</a> for the diagnosis of MS. The clinical histories of participating patients were reviewed and the following variables recorded: sex, age, sexual orientation, mucocutaneous lesions, extracutaneous manifestations, HIV status, viral load and HIV treatment, CD4+ T-lymphocyte count, histological pattern, venereal disease research laboratory (VDRL) test titer at diagnosis, treatment administered, and treatment response.ResultsA total of 332 patients were diagnosed with syphilis during the study period, of whom 202 were HIV-positive. Four cases corresponded to MS, accounting for 1.2% of the total number of diagnosed syphilis cases and 2% of syphilis cases in HIV-positive patients. The affected individuals were men who had sex with other men, were positive for HIV, and aged between 26 and 54 years (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). All had multiple ulcerated and necrotic nodules with palmoplantar involvement, and scalp involvement was observed in 3 cases (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). A clinical diagnosis of neurosyphilis was established in one case, and was confirmed by cerebrospinal fluid analysis.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Three of the 4 MS patients were not receiving HIV treatment at the moment of syphilis diagnosis, and one was unaware of his HIV-positive status. All patients had positive results in treponemal and nontreponemal tests, and a prozone phenomenon was observed in the 2 patients with the lowest CD4+ counts. Both these patients also displayed a Jarisch-Herxheimer reaction after antibiotic treatment.All patients had achieved complete clinical remission at the follow-up visit 1 month after treatment. A 4-fold decrease in VDRL titer was observed after 3 months in 2 patients and after 6 months in 1 patient. The fourth patient did not attend the scheduled follow-up visits. After 1 year of follow-up, none of the patients in follow-up had developed new lesions or showed increases in VDRL titer.DiscussionMS is an uncommon form of secondary syphilis, the exact incidence of which is unknown.<a class="elsevierStyleCrossRefs" href="#bib0075">1,2</a> The first case of MS in a HIV patient was reported in in 1988.<a class="elsevierStyleCrossRef" href="#bib0100">6</a> Since then, there has been an increase in the number of cases of MS in young, HIV-positive men.<a class="elsevierStyleCrossRefs" href="#bib0075">1,7</a> Immunological status does not appear to influence the development of MS; 80% of HIV patients with MS have a CD4+ cell count >200 cells/mm3 and almost none have had a previous opportunistic infection.<a class="elsevierStyleCrossRefs" href="#bib0080">2,8</a> These observations suggest that MS is the consequence of either an interaction between Treponema pallidum and the HIV virus or a functional immunological defect, rather than the result of a quantitative immunological deficit.<a class="elsevierStyleCrossRefs" href="#bib0090">4,9</a> In our series, only one patient had a CD4+ cell count <200 cells/mm3 at the time of diagnosis of syphilis, and CD4+ counts >500 cells/mm3 were detected in 2 patients, one of whom was receiving appropriate antiretroviral treatment and had an undetectable viral load. Cases of MS have also been described in nonimmunocompromised, HIV-negative individuals.<a class="elsevierStyleCrossRefs" href="#bib0105">7,10</a>Clinically, MS is characterized by disseminated pustules that evolve to ulcerated nodules, with a necrotic or hyperkeratotic surface, occasionally with a rupioid or ostraceous appearance.<a class="elsevierStyleCrossRefs" href="#bib0075">1,3</a> The lesions mainly affect the trunk and extremities, but involvement of the mucosae, palms, soles, and scalp is also common.<a class="elsevierStyleCrossRef" href="#bib0090">4</a> Fever and constitutional symptoms are frequent and often precede cutaneous signs.<a class="elsevierStyleCrossRef" href="#bib0125">11</a> The aggressiveness classically attributed to this form of syphilis is evidenced by the appearance of necrotic lesions that often leave varioliform scars after healing. These lesions, together with a high fever and general malaise, seem to be the only consistent features of MS that account for its more aggressive course compared with other forms of secondary syphilis. The extracutaneous involvement reported in these cases (neurosyphilis,<a class="elsevierStyleCrossRef" href="#bib0130">12</a> hepatitis,<a class="elsevierStyleCrossRef" href="#bib0125">11</a> and ocular involvement<a class="elsevierStyleCrossRefs" href="#bib0105">7,13</a>) has also been described in other forms of secondary syphilis, and there is no evidence in the literature to indicate that it is more frequent in MS.The clinical differential diagnosis can be challenging, and should include other infectious skin diseases (mainly infections caused by herpes family viruses, ecthyma gangrenosum, deep mycoses, mycobacteriosis, and leishmaniasis), lymphoproliferative skin diseases (cutaneous T-cell lymphoma, lymphomatoid papulosis, and pityriasis lichenoides et varioliformis acuta), and other diseases such as Reiter syndrome (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Fisher et al<a class="elsevierStyleCrossRef" href="#bib0095">5</a> defined the classical diagnostic criteria for MS: compatible macroscopic and microscopic skin lesions; a high VDRL titer; Jarisch-Herxheimer reaction upon starting antibiotic treatment; and rapid clinical resolution with treatment. All the cases in our series fulfilled these criteria, although 2 patients did not develop a Jarisch-Herxheimer reaction in response to antibiotic treatment. The absence of this reaction was not considered a reason to rule out a diagnosis of MS, nor does it appear to have any bearing on the specific clinical presentation. Indeed, the absence of the Jarisch-Herxheimer reaction has been described in many MS cases, and its presence may be difficult to confirm in patients who are already febrile and in a poor general condition as a consequence of the disease.Histologically, MS is similar to other forms of secondary syphilis, and is characterized by the presence of a dense inflammatory infiltrate, sometimes in the context of a lichenoid dermatitis pattern, with a predominance of lymphocytes and plasma cells and occasional granulomas.<a class="elsevierStyleCrossRef" href="#bib0090">4</a> Ulcerated lesions may be caused by vascular involvement secondary to infection, which gives rise to infarcts in medium-sized arteries.<a class="elsevierStyleCrossRef" href="#bib0110">8</a> In our series, we observed vascular thrombosis (without signs of vasculitis) in only one case, probably because these findings depend on the lesion biopsied and its stage of evolution. Classically, T pallidum is absent from MS histology (probably due to the intensity of the inflammatory infiltrate).<a class="elsevierStyleCrossRef" href="#bib0125">11</a> However, in our series we detected its presence by immunohistochemistry in 2 patients (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>There is no evidence in the literature indicating a greater incidence of treatment failure and neurosyphilis in MS as compared with other forms of secondary syphilis in patients with HIV. Although the most frequently reported regimen for the treatment of these cases is 3 doses of intramuscular penicillin benzathine (2.4 million units), treatment with a single dose results in a comparable response and has no effect on the rate of treatment failure.<a class="elsevierStyleCrossRef" href="#bib0090">4</a> In these patients it thus seems appropriate to opt for the therapeutic approach recommended in current clinical guidelines<a class="elsevierStyleCrossRef" href="#bib0140">14</a> for the management of HIV-positive patients with syphilis. Therefore, lumbar puncture should always be performed in MS patients with signs or symptoms suggestive of neurosyphilis or ocular involvement. Lumbar puncture is also recommended in HIV patients with late or unconfirmed syphilis, with a CD4+ count ≤350 cells/mm3 and/or persistent VDRL/rapid plasma reagin (RPR) titers >1:32 after treatment, in the absence of neurological signs.<a class="elsevierStyleCrossRef" href="#bib0140">14</a>ConclusionMS is an uncommon variant of secondary syphilis that should be included in the differential diagnosis of HIV patients with ulcerated and necrotic lesions. In our series, MS accounted for 1.2% of all patients diagnosed with syphilis. MS is characterized not by aggressive systemic manifestations but by aggressive cutaneous lesions that heal leaving varioliform scars. In the absence of neurosyphilis, the proposed treatment is the same as that recommended for HIV-negative patients with secondary syphilis. A single dose of intramuscular penicillin is sufficient in cases of early syphilis.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1174044" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1174046" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1097964" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1174045" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0015" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1097963" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and Methods" ] 7 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-12" "fechaAceptado" => "2018-02-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1097964" "palabras" => array:4 [ 0 => "Syphilis" 1 => "Sexually transmitted infections" 2 => "Human immunodeficiency virus" 3 => "Epidemiology" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1097963" "palabras" => array:4 [ 0 => "Sífilis" 1 => "Infecciones de transmisión sexual" 2 => "Virus de la inmunodeficiencia humana" 3 => "Epidemiología" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La sífilis maligna es una forma infrecuente de sífilis secundaria asociada a la infección por el VIH, caracterizada clínicamente por nódulos necróticos y lesiones ulceradas generalizadas. Presentamos 4 pacientes diagnosticados de sífilis maligna tras revisar los casos de sífilis diagnosticados en nuestro centro entre 2012 y 2016. Describimos los aspectos epidemiológicos, clínicos, histopatológicos y serológicos, así como su relación con el VIH y la respuesta al tratamiento. Aunque se trate de una forma de sífilis poco frecuente, en los últimos años ha aumentado el número de casos publicados, principalmente pacientes jóvenes infectados por el VIH. Es necesario incluir la sífilis maligna en el diagnóstico diferencial de pacientes infectados por el VIH con lesiones ulceradas y necróticas." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Fustà-Novell X, Morgado-Carrasco D, Barreiro-Capurro A, Manzardo C, Alsina-Gibert M, Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona, et al. Syphilis Maligna: A Presentation to Bear in Mind. Actas Dermosifiliogr. 2019;110:232–237." ] 1 => array:3 [ "etiqueta" => "1" "nota" => "Véase el Anexo A." "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "Irene Fuertes-de Vega, José-Luís Blanco, Anna González, Asunción Moreno, Miriam Álvarez, Jordi Bosch" "etiqueta" => "Annex A" "titulo" => "Members of the Working Group on Sexually Transmitted Infections, Hospital Clínic de Barcelona" "identificador" => "sec0035" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2452 "Ancho" => 2501 "Tamanyo" => 719593 ] ] "descripcion" => array:1 [ "en" => "Skin lesions in Patients 1 (A, B) and 2 (C, D)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2264 "Ancho" => 2501 "Tamanyo" => 591511 ] ] "descripcion" => array:1 [ "en" => "Skin lesions in Patients 3 (A, B) and 4 (C, D)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1164 "Ancho" => 2094 "Tamanyo" => 228447 ] ] "descripcion" => array:1 [ "en" => "Schematic showing diagnostic and treatment approach for suspected malignant syphilis. Abbreviations: F, fundus; HIV, human immunodeficiency virus; IHC, immunohistochemistry; IM, intramuscular; IV, intravenous; J-H, Jarisch-Herxheimer; LP, lumbar puncture; MU, millions of units; PCR, polymerase chain reaction; PG, penicillin G; PLEVA, pityriasis lichenoides et varioliformis acuta; VZV, varicella-zoster virus." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1675 "Ancho" => 1501 "Tamanyo" => 582536 ] ] "descripcion" => array:1 [ "en" => "Histology of biopsy from Patient 2. A, Epidermis showing marked spongiotic changes. Predominantly histiocytic inflammatory infiltrate is evident in the superficial dermis (hematoxylin-eosin, original magnification ×100). B, Visualization of abundant spirochetes by immunostaining for Treponema pallidum (Treponema immunohistochemistry, original magnification ×100)." ] ] 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: HIV, human immunodeficiency virus; M, male; MSM, men who have sex with men; MU, millions of units; VDRL, venereal disease research laboratory test." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \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">Sex \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">Age, y \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">Mucocutaneous Signs \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">Systemic Signs \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">Days Since Lesion Onset \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">HIV Status \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">HIV Viral Load, Copies/mL \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">CD4+ Count, Cells/mm3 \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">Histological Pattern (Cellularity of Dermal Inflammatory Infiltrate) \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">VDRL Titer \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><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Course \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">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M (MSM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ulcerated and necrotic nodules, palmoplantar and scalp involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever (>38°C) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ (not in treatment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 950 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">171 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lichenoid dermatitis (lymphocytes, histiocytes, plasma cells). Treponema immunostaining + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1:128 (prozone phenomenon) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intramuscular penicillin G benzathine, 2.4 MU (3 doses) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Jarisch-Herxheimer reaction. Complete clinical response \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">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M (MSM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ulcerated and necrotic nodules, palmoplantar, ungueal, and scalp involvement. Oral erosions. Genital involvement, seborrheic dermatitis-like lesions. Perianal condyloma lata \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever (>38°C) Syphilitic uveitis. Neurosyphilis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ (not in treatment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 350 000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">250 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Spongiotic dermatitis (histiocytes, plasma cells). Treponema immunostaining + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1:250 (prozone phenomenon) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intravenous aqueous penicillin G, 24 MU (daily for 15 days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Jarisch-Herxheimer reaction. Complete clinical response \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">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M (MSM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ulcerated and necrotic nodules, hyperkeratotic nodules, palmoplantar involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever (>38°C) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ (unknown, not in treatment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71 300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">697 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lichenoid dermatitis (lymphocytes, histiocytes, plasma cells). Treponema immunostaining - \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1:512 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intramuscular penicillin G benzathine, 2.4 MU (3 doses) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete clinical response \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">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M (MSM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ulcerated and necrotic nodules, palmar and scalp involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low-grade fever, night sweats \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ (in treatment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">790 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cutaneous abscess (lymphocytes, histiocytes, plasma cells). Treponema immunostaining - \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1:256 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intramuscular penicillin G benzathine, 2.4 MU (1 dose) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete clinical response \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2003839.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical and Histological Characteristics, Blood Test Abnormalities, Treatment, and Clinical Course" ] ] 5 => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1085 "Ancho" => 1095 "Tamanyo" => 145985 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lues maligna in early HIV infection case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.D. 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Estadísticas

Brief Comunications

Syphilis Maligna: A Presentation to Bear in Mind

Sífilis maligna, una presentación de sífilis a tener en cuenta

X. Fustà-Novella, D. Morgado-Carrascoa, A. Barreiro-Capurroa, C. Manzardob, M. Alsina-Giberta,

Autor para correspondencia

malsina@clinic.cat

Corresponding author.

, Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona a,b,c,1

a Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España

b Servicio de Enfermedades Infecciosas, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España

c Servicio de Microbiología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España

Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Malignant syphilis &#40;MS&#41; is an uncommon form of secondary syphilis that presents with ulcerated and necrotic skin lesions&#46; The last 2 decades have seen an increase in the number of published cases&#44; mainly in patients with human immunodeficiency virus &#40;HIV&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#8211;4</span></a> Literature on MS is scarce&#44; and is limited mainly to isolated case reports&#46; It is therefore difficult to determine its frequency&#44; pathogenesis&#44; and clinical spectrum&#46; Here we describe the clinical and histological characteristics and treatment response of MS cases diagnosed in our hospital&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Material and Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">We performed a retrospective observational study of patients diagnosed with syphilis in our hospital during the period 2012 to 2016&#46; We selected patients who had ulcerated&#44; necrotic skin lesions compatible with MS and fulfilled the criteria of Fisher et al<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> for the diagnosis of MS&#46; The clinical histories of participating patients were reviewed and the following variables recorded&#58; sex&#44; age&#44; sexual orientation&#44; mucocutaneous lesions&#44; extracutaneous manifestations&#44; HIV status&#44; viral load and HIV treatment&#44; CD4<span class="elsevierStyleSup">&#43;</span> T-lymphocyte count&#44; histological pattern&#44; venereal disease research laboratory &#40;VDRL&#41; test titer at diagnosis&#44; treatment administered&#44; and treatment response&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">A total of 332 patients were diagnosed with syphilis during the study period&#44; of whom 202 were HIV-positive&#46; Four cases corresponded to MS&#44; accounting for 1&#46;2&#37; of the total number of diagnosed syphilis cases and 2&#37; of syphilis cases in HIV-positive patients&#46; The affected individuals were men who had sex with other men&#44; were positive for HIV&#44; and aged between 26 and 54 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All had multiple ulcerated and necrotic nodules with palmoplantar involvement&#44; and scalp involvement was observed in 3 cases &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; A clinical diagnosis of neurosyphilis was established in one case&#44; and was confirmed by cerebrospinal fluid analysis&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Three of the 4 MS patients were not receiving HIV treatment at the moment of syphilis diagnosis&#44; and one was unaware of his HIV-positive status&#46; All patients had positive results in treponemal and nontreponemal tests&#44; and a prozone phenomenon was observed in the 2 patients with the lowest CD4<span class="elsevierStyleSup">&#43;</span> counts&#46; Both these patients also displayed a Jarisch-Herxheimer reaction after antibiotic treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients had achieved complete clinical remission at the follow-up visit 1 month after treatment&#46; A 4-fold decrease in VDRL titer was observed after 3 months in 2 patients and after 6 months in 1 patient&#46; The fourth patient did not attend the scheduled follow-up visits&#46; After 1 year of follow-up&#44; none of the patients in follow-up had developed new lesions or showed increases in VDRL titer&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">MS is an uncommon form of secondary syphilis&#44; the exact incidence of which is unknown&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#44;2</span></a> The first case of MS in a HIV patient was reported in in 1988&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> Since then&#44; there has been an increase in the number of cases of MS in young&#44; HIV-positive men&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#44;7</span></a> Immunological status does not appear to influence the development of MS&#59; 80&#37; of HIV patients with MS have a CD4<span class="elsevierStyleSup">&#43;</span> cell count &#62;200&#160;cells&#47;mm<span class="elsevierStyleSup">3</span> and almost none have had a previous opportunistic infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;8</span></a> These observations suggest that MS is the consequence of either an interaction between <span class="elsevierStyleItalic">Treponema pallidum</span> and the HIV virus or a functional immunological defect&#44; rather than the result of a quantitative immunological deficit&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">4&#44;9</span></a> In our series&#44; only one patient had a CD4<span class="elsevierStyleSup">&#43;</span> cell count &#60;200&#160;cells&#47;mm<span class="elsevierStyleSup">3</span> at the time of diagnosis of syphilis&#44; and CD4<span class="elsevierStyleSup">&#43;</span> counts &#62;500&#160;cells&#47;mm<span class="elsevierStyleSup">3</span> were detected in 2 patients&#44; one of whom was receiving appropriate antiretroviral treatment and had an undetectable viral load&#46; Cases of MS have also been described in nonimmunocompromised&#44; HIV-negative individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">7&#44;10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Clinically&#44; MS is characterized by disseminated pustules that evolve to ulcerated nodules&#44; with a necrotic or hyperkeratotic surface&#44; occasionally with a rupioid or ostraceous appearance&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#44;3</span></a> The lesions mainly affect the trunk and extremities&#44; but involvement of the mucosae&#44; palms&#44; soles&#44; and scalp is also common&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> Fever and constitutional symptoms are frequent and often precede cutaneous signs&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> The aggressiveness classically attributed to this form of syphilis is evidenced by the appearance of necrotic lesions that often leave varioliform scars after healing&#46; These lesions&#44; together with a high fever and general malaise&#44; seem to be the only consistent features of MS that account for its more aggressive course compared with other forms of secondary syphilis&#46; The extracutaneous involvement reported in these cases &#40;neurosyphilis&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> hepatitis&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> and ocular involvement<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">7&#44;13</span></a>&#41; has also been described in other forms of secondary syphilis&#44; and there is no evidence in the literature to indicate that it is more frequent in MS&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The clinical differential diagnosis can be challenging&#44; and should include other infectious skin diseases &#40;mainly infections caused by herpes family viruses&#44; ecthyma gangrenosum&#44; deep mycoses&#44; mycobacteriosis&#44; and leishmaniasis&#41;&#44; lymphoproliferative skin diseases &#40;cutaneous T-cell lymphoma&#44; lymphomatoid papulosis&#44; and pityriasis lichenoides et varioliformis acuta&#41;&#44; and other diseases such as Reiter syndrome &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Fisher et al<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> defined the classical diagnostic criteria for MS&#58; compatible macroscopic and microscopic skin lesions&#59; a high VDRL titer&#59; Jarisch-Herxheimer reaction upon starting antibiotic treatment&#59; and rapid clinical resolution with treatment&#46; All the cases in our series fulfilled these criteria&#44; although 2 patients did not develop a Jarisch-Herxheimer reaction in response to antibiotic treatment&#46; The absence of this reaction was not considered a reason to rule out a diagnosis of MS&#44; nor does it appear to have any bearing on the specific clinical presentation&#46; Indeed&#44; the absence of the Jarisch-Herxheimer reaction has been described in many MS cases&#44; and its presence may be difficult to confirm in patients who are already febrile and in a poor general condition as a consequence of the disease&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Histologically&#44; MS is similar to other forms of secondary syphilis&#44; and is characterized by the presence of a dense inflammatory infiltrate&#44; sometimes in the context of a lichenoid dermatitis pattern&#44; with a predominance of lymphocytes and plasma cells and occasional granulomas&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> Ulcerated lesions may be caused by vascular involvement secondary to infection&#44; which gives rise to infarcts in medium-sized arteries&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> In our series&#44; we observed vascular thrombosis &#40;without signs of vasculitis&#41; in only one case&#44; probably because these findings depend on the lesion biopsied and its stage of evolution&#46; Classically&#44; <span class="elsevierStyleItalic">T pallidum</span> is absent from MS histology &#40;probably due to the intensity of the inflammatory infiltrate&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> However&#44; in our series we detected its presence by immunohistochemistry in 2 patients &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">There is no evidence in the literature indicating a greater incidence of treatment failure and neurosyphilis in MS as compared with other forms of secondary syphilis in patients with HIV&#46; Although the most frequently reported regimen for the treatment of these cases is 3 doses of intramuscular penicillin benzathine &#40;2&#46;4 million units&#41;&#44; treatment with a single dose results in a comparable response and has no effect on the rate of treatment failure&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> In these patients it thus seems appropriate to opt for the therapeutic approach recommended in current clinical guidelines<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> for the management of HIV-positive patients with syphilis&#46; Therefore&#44; lumbar puncture should always be performed in MS patients with signs or symptoms suggestive of neurosyphilis or ocular involvement&#46; Lumbar puncture is also recommended in HIV patients with late or unconfirmed syphilis&#44; with a CD4<span class="elsevierStyleSup">&#43;</span> count&#160;&#8804;350 cells&#47;mm<span class="elsevierStyleSup">3</span> and&#47;or persistent VDRL&#47;rapid plasma reagin &#40;RPR&#41; titers &#62;1&#58;32 after treatment&#44; in the absence of neurological signs&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="par0060" class="elsevierStylePara elsevierViewall">MS is an uncommon variant of secondary syphilis that should be included in the differential diagnosis of HIV patients with ulcerated and necrotic lesions&#46; In our series&#44; MS accounted for 1&#46;2&#37; of all patients diagnosed with syphilis&#46; MS is characterized not by aggressive systemic manifestations but by aggressive cutaneous lesions that heal leaving varioliform scars&#46; In the absence of neurosyphilis&#44; the proposed treatment is the same as that recommended for HIV-negative patients with secondary syphilis&#46; A single dose of intramuscular penicillin is sufficient in cases of early syphilis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection&#46; Clinically&#44; it is characterized by necrotic nodules and generalized ulcerated lesions&#46; We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016&#46; We describe the epidemiologic&#44; clinical&#44; histiopathologic&#44; and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection&#46; Although malignant syphilis is uncommon&#44; there has been an increase in the number of cases published in recent years&#44; particularly in young HIV-positive patients&#46; Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated&#44; necrotic lesions&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La s&#237;filis maligna es una forma infrecuente de s&#237;filis secundaria asociada a la infecci&#243;n por el VIH&#44; caracterizada cl&#237;nicamente por n&#243;dulos necr&#243;ticos y lesiones ulceradas generalizadas&#46; Presentamos 4 pacientes diagnosticados de s&#237;filis maligna tras revisar los casos de s&#237;filis diagnosticados en nuestro centro entre 2012 y 2016&#46; Describimos los aspectos epidemiol&#243;gicos&#44; cl&#237;nicos&#44; histopatol&#243;gicos y serol&#243;gicos&#44; as&#237; como su relaci&#243;n con el VIH y la respuesta al tratamiento&#46; Aunque se trate de una forma de s&#237;filis poco frecuente&#44; en los &#250;ltimos a&#241;os ha aumentado el n&#250;mero de casos publicados&#44; principalmente pacientes j&#243;venes infectados por el VIH&#46; Es necesario incluir la s&#237;filis maligna en el diagn&#243;stico diferencial de pacientes infectados por el VIH con lesiones ulceradas y necr&#243;ticas&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Fust&#224;-Novell X&#44; Morgado-Carrasco D&#44; Barreiro-Capurro A&#44; Manzardo C&#44; Alsina-Gibert M&#44; Miembros del Grupo de Trabajo de Infecciones de Transmisi&#243;n Sexual del Hospital Cl&#237;nic de Barcelona&#44; et al&#46; Syphilis Maligna&#58; A Presentation to Bear in Mind&#46; Actas Dermosifiliogr&#46; 2019&#59;110&#58;232&#8211;237&#46;</p>"
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            "titulo" => "Members of the Working Group on Sexually Transmitted Infections&#44; Hospital Cl&#237;nic de Barcelona"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Schematic showing diagnostic and treatment approach for suspected malignant syphilis&#46; Abbreviations&#58; F&#44; fundus&#59; HIV&#44; human immunodeficiency virus&#59; IHC&#44; immunohistochemistry&#59; IM&#44; intramuscular&#59; IV&#44; intravenous&#59; J-H&#44; Jarisch-Herxheimer&#59; LP&#44; lumbar puncture&#59; MU&#44; millions of units&#59; PCR&#44; polymerase chain reaction&#59; PG&#44; penicillin G&#59; PLEVA&#44; pityriasis lichenoides et varioliformis acuta&#59; VZV&#44; varicella-zoster virus&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Histology of biopsy from Patient 2&#46; A&#44; Epidermis showing marked spongiotic changes&#46; Predominantly histiocytic inflammatory infiltrate is evident in the superficial dermis &#40;hematoxylin-eosin&#44; original magnification &#215;100&#41;&#46; B&#44; Visualization of abundant spirochetes by immunostaining for <span class="elsevierStyleItalic">Treponema pallidum</span> &#40;<span class="elsevierStyleItalic">Treponema</span> immunohistochemistry&#44; original magnification &#215;100&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; HIV&#44; human immunodeficiency virus&#59; M&#44; male&#59; MSM&#44; men who have sex with men&#59; MU&#44; millions of units&#59; VDRL&#44; venereal disease research laboratory test&#46;</p>"
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                  <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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient&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">Sex&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">Age&#44; y&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">Mucocutaneous Signs&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">Systemic Signs&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">Days Since Lesion Onset&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">HIV Status&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">HIV Viral Load&#44; Copies&#47;mL&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">CD4<span class="elsevierStyleSup">&#43;</span> Count&#44; Cells&#47;mm<span class="elsevierStyleSup">3</span>&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">Histological Pattern &#40;Cellularity of Dermal Inflammatory Infiltrate&#41;&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">VDRL Titer&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><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Course&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">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M &#40;MSM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ulcerated and necrotic nodules&#44; palmoplantar and scalp involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever &#40;&#62;38&#176;C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43; &#40;not in treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 950&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lichenoid dermatitis &#40;lymphocytes&#44; histiocytes&#44; plasma cells&#41;&#46; <span class="elsevierStyleItalic">Treponema</span> immunostaining &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;128 &#40;prozone phenomenon&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intramuscular penicillin G benzathine&#44; 2&#46;4&#160;MU &#40;3 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Jarisch-Herxheimer reaction&#46; Complete clinical response&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">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M &#40;MSM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ulcerated and necrotic nodules&#44; palmoplantar&#44; ungueal&#44; and scalp involvement&#46; Oral erosions&#46; Genital involvement&#44; seborrheic dermatitis-like lesions&#46; Perianal condyloma lata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever &#40;&#62;38&#176;C&#41; Syphilitic uveitis&#46; Neurosyphilis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43; &#40;not in treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 350 000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">250&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spongiotic dermatitis &#40;histiocytes&#44; plasma cells&#41;&#46; <span class="elsevierStyleItalic">Treponema</span> immunostaining &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;250 &#40;prozone phenomenon&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intravenous aqueous penicillin G&#44; 24&#160;MU &#40;daily for 15 days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Jarisch-Herxheimer reaction&#46; Complete clinical response&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">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M &#40;MSM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ulcerated and necrotic nodules&#44; hyperkeratotic nodules&#44; palmoplantar involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever &#40;&#62;38&#176;C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43; &#40;unknown&#44; not in treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71 300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">697&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lichenoid dermatitis &#40;lymphocytes&#44; histiocytes&#44; plasma cells&#41;&#46; <span class="elsevierStyleItalic">Treponema</span> immunostaining -&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;512&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intramuscular penicillin G benzathine&#44; 2&#46;4&#160;MU &#40;3 doses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Complete clinical response&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">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M &#40;MSM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ulcerated and necrotic nodules&#44; palmar and scalp involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Low-grade fever&#44; night sweats&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43; &#40;in treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">790&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cutaneous abscess &#40;lymphocytes&#44; histiocytes&#44; plasma cells&#41;&#46; <span class="elsevierStyleItalic">Treponema</span> immunostaining -&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;256&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intramuscular penicillin G benzathine&#44; 2&#46;4&#160;MU &#40;1 dose&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Complete clinical response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                            4 => "A&#46; Zembowicz"
                            5 => "D&#46; Kroshinsky"
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                            0 => "M&#46;J&#46; Romero-Jim&#233;nez"
                            1 => "I&#46; Su&#225;rez Lozano"
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                            0 => "P&#46;M&#46; Cid"
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                            0 => "B&#46; De Unamuno Bustos"
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                            2 => "J&#46;L&#46;S&#46; Carazo"
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                        "fecha" => "2014"
                        "volumen" => "53"
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Información del artículo

ISSN: 15782190
Idioma original: Inglés

DOI:10.1016/j.adengl.2019.02.001

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