Case and Research Letter
Usefulness of Immunohistochemial Staining With Antitrepenomal Antibodies in the Diagnosis of Syphilis
Utilidad de la inmunohistoquímica con anticuerpos antitreponema en el diagnóstico de la sífilis
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Imagen superior (tinción hematoxilina-eosina × 50) donde se aprecia un intenso infiltrado inflamatorio con predominio de células plasmáticas. En la parte inferior la misma biopsia con IHQ (× 400) donde se observa la infiltración de treponemas que aparecen como estructuras arrosariadas marronáceas.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Hernández, R. Fúnez, B. Repiso, M. Frieyro" "autores" => array:4 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Hernández" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Fúnez" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Repiso" ] 3 => array:2 [ "nombre" => "M." 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Hernández, R. Fúnez, B. Repiso, M. Frieyro" "autores" => array:4 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Hernández" "email" => array:1 [ 0 => "chernandez@aedv.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R." "apellidos" => "Fúnez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "B." "apellidos" => "Repiso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Frieyro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Costa del Sol, Marbella, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicios de Anatomía Patológica, Hospital Costa del Sol, Marbella, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Utilidad de la inmunohistoquímica con anticuerpos antitreponema en el diagnóstico de la sífilis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 950 "Ancho" => 951 "Tamanyo" => 233516 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Biopsy of the lesion shown in Figure 1. Upper image: intense inflammatory infiltrate with a predominance of plasma cells (hematoxylin-eosin, original magnification × 50). Lower panel: IHC of the same biopsy (original magnification × 400) showing infiltration of treponemata, which appear as brownish bead-like structures.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Syphilis is a sexually transmitted infection (STI) caused by the spirochete <span class="elsevierStyleItalic">Treponema pallidum pallidum</span>. Recent years have seen a resurgence of syphilis. This is mainly due to an increased number of cases diagnosed in men who have sex with men (MSM).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Infection is associated with erratic condom use and a high number of sexual partners in the months before diagnosis.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In Spain the incidence of syphilis has tripled since the beginning of this century, increasing from 1.96 to 5.70 per 100 000 population between 1998 and 2008..<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Even with effective treatment, the disease remains a significant public health problem with high associated economic costs.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Correct diagnosis is crucial in order to start antibiotic therapy as soon as possible and thus prevent new infections and stop the progression of the disease and associated sequelae.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Accordingly, new, more effective diagnostic techniques are required.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Traditionally the diagnosis of syphilis is based on a combination of clinical signs and symptoms, serological tests, and direct detection of the organism using dark field microscopy and silver impregnation techniques.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,5,6</span></a> A definitive diagnosis can be reached only by direct detection of the microorganism in infected tissues.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">These diagnostic methods can yield conflicting results in many clinical situations. Obtaining the clinical history of a patient with an STI can be difficult due to feelings of embarrassment or guilt.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Moreover, syphilis has a wide range of clinical manifestations, which has earned it the epigram <span class="elsevierStyleItalic">the great imitator</span>. It can present with very atypical clinical features and hence be mistaken for genital ulcers or other different types of rash.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6,8</span></a> Clinical diagnosis thus depends on the experience of the physician and the presence of lesions.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Serology, using a combination of nontreponemal tests (Venereal Disease Research Laboratory and rapid plasma reagin) and treponemal tests (fluorescent treponemal antibody absorption and <span class="elsevierStyleItalic">Treponema pallidum</span> particle agglutination assay), has become the most commonly used means of indirect diagnosis, with proven benefits for the diagnosis and monitoring of patients after the initiation of treatment, although several acute and chronic infections can produce false positives in nontreponemal tests While treponemal tests are highly specific and sensitive (almost 100%) in cases of secondary syphilis, sensitivity and/or specificity are lower in the early stages of infection, in cases of congenital and tertiary syphilis, neurosyphilis with HIV coinfection, and in other immunosuppressive conditions.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,5,6,9</span></a> The increasingly common association of syphilis with HIV should be noted, given the confusion that can arise due to serological test results in these cases and the quite atypical clinical course.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">For direct detection of <span class="elsevierStyleItalic">T pallidum</span> dark field microscopy is sensitive but not specific, and requires trained personnel. Silver impregnation techniques are of low sensitivity (33% to 71%) and low specificity. Moreover, they give rise to numerous field artifacts and lack the necessary specificity to identify contaminant nontreponemal spirochetes (e.g., in oral mucosa).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6,9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Several recently published findings support the role of biopsy with immunohistochemistry (IHC) using antitreponemal antibodies for the diagnosis of syphilis. One study comparing IHC with silver impregnation techniques concluded that the former was more sensitive.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Indeed, the sensitivity of IHC is over 90% in most cases, although lower values (71%) have been reported in some studies.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Sensitivity and specificity are highest in early primary and secondary syphilis (when spirochetes are found in large quantities), but diminish in later stages due to decreases in the number of microorganisms in the lesions.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> IHC can distinguish syphilis lesions from other unrelated lesions, which may appear in patients with both true and false positive serology for <span class="elsevierStyleItalic">T pallidum.</span> Moreover, this technique permits the detection of spirochetes in the skin, although cross-reactivity with <span class="elsevierStyleItalic">Borrelia</span> species is possible.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Furthermore, IHC is a relatively rapid and inexpensive technique, with results available in about 48<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Here we present 5 clinical cases of patients treated in our STI outpatient clinic between January 2009 and January 2012 with a final diagnosis of syphilis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>); in all cases IHC was crucial for accurate diagnosis. The selected cases are representative of those seen in everyday practice, in terms of their clinical manifestations and/or doubtful or even negative serology, and thus were difficult to diagnose. Case 1 was an HIV-positive patient with a negative treponemal test, a lesion suggestive of syphilitic chancre, and no lymph node enlargement. This test result may have been due to the window period, or may reflect a false negative influenced by HIV co-infection. In case 2, the patient had a lesion suggestive of syphilitic chancre, but a negative enzyme-linked immunosorbent assay (ELISA), which was also probably due to the window period. Similarly, the negative ELISA in case 3, despite lesions suggestive of secondary syphilis, was probably a rare case of a false negative using this technique. The patient in case 4 presented rarely seen clinical features with a faint macular rash without palmoplantar involvement. Finally, case 5 (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>) is an example of atypical extragenital clinical manifestations.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">IHC offers increased sensitivity and specificity compared with conventional techniques for the detection of <span class="elsevierStyleItalic">T pallidum</span>.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–6,8–10</span></a> Although this technique is not a widely used diagnostic method and we do not recommend its routine use, these 5 cases highlight its utility, especially in HIV patients or immunosuppressed patients in general, in those with secondary syphilis with negative and/or dubious serology, in cases with atypical clinical features (including cases of extragenital syphilis), and in the early stages of the disease.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Hernández C, Fúnez R, Repiso B, Frieyro M. Utilidad de la inmunohistoquímica con anticuerpos antitreponema en el diagnóstico de la sífilis. Actas Dermosifiliogr. 2013;104:926–928.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 607 "Ancho" => 801 "Tamanyo" => 94772 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Case 5. Whitish papillary lesions on the lateral border of the tongue.</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" => 950 "Ancho" => 951 "Tamanyo" => 233516 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Biopsy of the lesion shown in Figure 1. Upper image: intense inflammatory infiltrate with a predominance of plasma cells (hematoxylin-eosin, original magnification × 50). Lower panel: IHC of the same biopsy (original magnification × 400) showing infiltration of treponemata, which appear as brownish bead-like structures.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ELISA, enzyme-linked immunosorbent assay; F, female; HIV, human immunodeficiency virus; IHC, immunohistochemistry; M, male; NP, not performed; RPR, rapid plasma regain; TPHA, <span class="elsevierStyleItalic">Treponema pallidum</span> haemagglutination test.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical Cases \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">Sex \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">Age \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">Clinical Features \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">HIV \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">ELISA \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">RPR \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">TPHA \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">Case Details \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">IHC \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">Case 1 \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"><span class="elsevierStyleSmallCaps">M</span> \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">42 \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">Painful genital ulcer Swollen lymph nodes \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">+ \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">+ \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">1/4 \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">− \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">TPHA \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">+ \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">Case 2 \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"><span class="elsevierStyleSmallCaps">M</span> \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">54 \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">Two painful genital ulcers Swollen lymph nodes \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">− \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">− \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">NP \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">NP \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">ELISA with typical clinical features \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">+ \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">Case 3 \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"><span class="elsevierStyleSmallCaps">M</span> \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">37 \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">Plaques with depressed center and multiple non-painful ulcers in the pubic area \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"><span class="elsevierStyleBold">−</span> \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"><span class="elsevierStyleBold">−</span> \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">NP \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">NP \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">ELISA with typical clinical features \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">+ \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">Case 4 \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"><span class="elsevierStyleSmallCaps">M</span> \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">47 \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">Faint macular rash without palmoplantar 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"><span class="elsevierStyleBold">−</span> \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">+ \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">1/64 \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">1/2560 \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">Atypical clinical features \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">+ \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">Case 5 \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">F \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">55 \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">Whitish papillary lesions on the lateral border of the tongue \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"><span class="elsevierStyleBold">−</span> \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">NP \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">1/128 \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">1/2560 \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">Atypical clinical features \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">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab430513.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clinical and Serological Features of the 5 Clinical Cases.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 16 | 7 | 23 |
| 2024 Octubre | 108 | 40 | 148 |
| 2024 Septiembre | 123 | 19 | 142 |
| 2024 Agosto | 132 | 52 | 184 |
| 2024 Julio | 124 | 38 | 162 |
| 2024 Junio | 148 | 58 | 206 |
| 2024 Mayo | 101 | 35 | 136 |
| 2024 Abril | 111 | 19 | 130 |
| 2024 Marzo | 113 | 27 | 140 |
| 2024 Febrero | 104 | 37 | 141 |
| 2024 Enero | 88 | 26 | 114 |
| 2023 Diciembre | 75 | 24 | 99 |
| 2023 Noviembre | 80 | 40 | 120 |
| 2023 Octubre | 86 | 36 | 122 |
| 2023 Septiembre | 88 | 32 | 120 |
| 2023 Agosto | 73 | 27 | 100 |
| 2023 Julio | 73 | 28 | 101 |
| 2023 Junio | 57 | 20 | 77 |
| 2023 Mayo | 76 | 24 | 100 |
| 2023 Abril | 78 | 30 | 108 |
| 2023 Marzo | 60 | 20 | 80 |
| 2023 Febrero | 65 | 25 | 90 |
| 2023 Enero | 75 | 23 | 98 |
| 2022 Diciembre | 76 | 40 | 116 |
| 2022 Noviembre | 23 | 21 | 44 |
| 2022 Octubre | 27 | 30 | 57 |
| 2022 Septiembre | 29 | 46 | 75 |
| 2022 Agosto | 23 | 32 | 55 |
| 2022 Julio | 45 | 41 | 86 |
| 2022 Junio | 21 | 25 | 46 |
| 2022 Mayo | 59 | 44 | 103 |
| 2022 Abril | 73 | 53 | 126 |
| 2022 Marzo | 137 | 57 | 194 |
| 2022 Febrero | 85 | 28 | 113 |
| 2022 Enero | 79 | 37 | 116 |
| 2021 Diciembre | 47 | 27 | 74 |
| 2021 Noviembre | 70 | 52 | 122 |
| 2021 Octubre | 84 | 51 | 135 |
| 2021 Septiembre | 54 | 46 | 100 |
| 2021 Agosto | 42 | 22 | 64 |
| 2021 Julio | 44 | 40 | 84 |
| 2021 Junio | 65 | 29 | 94 |
| 2021 Mayo | 47 | 37 | 84 |
| 2021 Abril | 142 | 42 | 184 |
| 2021 Marzo | 111 | 27 | 138 |
| 2021 Febrero | 69 | 27 | 96 |
| 2021 Enero | 56 | 20 | 76 |
| 2020 Diciembre | 50 | 23 | 73 |
| 2020 Noviembre | 40 | 13 | 53 |
| 2020 Octubre | 41 | 17 | 58 |
| 2020 Septiembre | 34 | 14 | 48 |
| 2020 Agosto | 26 | 24 | 50 |
| 2020 Julio | 40 | 13 | 53 |
| 2020 Junio | 37 | 24 | 61 |
| 2020 Mayo | 24 | 15 | 39 |
| 2020 Abril | 34 | 17 | 51 |
| 2020 Marzo | 31 | 17 | 48 |
| 2020 Febrero | 4 | 6 | 10 |
| 2020 Enero | 4 | 6 | 10 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 4 | 1 | 5 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 8 | 2 | 10 |
| 2019 Agosto | 3 | 3 | 6 |
| 2019 Julio | 4 | 5 | 9 |
| 2019 Junio | 6 | 14 | 20 |
| 2019 Mayo | 4 | 15 | 19 |
| 2019 Abril | 2 | 14 | 16 |
| 2019 Marzo | 2 | 8 | 10 |
| 2019 Febrero | 4 | 4 | 8 |
| 2019 Enero | 1 | 1 | 2 |
| 2018 Diciembre | 0 | 7 | 7 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 4 | 0 | 4 |
| 2018 Marzo | 14 | 0 | 14 |
| 2018 Febrero | 61 | 6 | 67 |
| 2018 Enero | 75 | 4 | 79 |
| 2017 Diciembre | 77 | 4 | 81 |
| 2017 Noviembre | 72 | 6 | 78 |
| 2017 Octubre | 67 | 8 | 75 |
| 2017 Septiembre | 74 | 4 | 78 |
| 2017 Agosto | 74 | 8 | 82 |
| 2017 Julio | 65 | 9 | 74 |
| 2017 Junio | 68 | 9 | 77 |
| 2017 Mayo | 84 | 8 | 92 |
| 2017 Abril | 70 | 4 | 74 |
| 2017 Marzo | 60 | 5 | 65 |
| 2017 Febrero | 59 | 11 | 70 |
| 2017 Enero | 60 | 7 | 67 |
| 2016 Diciembre | 71 | 6 | 77 |
| 2016 Noviembre | 87 | 5 | 92 |
| 2016 Octubre | 103 | 8 | 111 |
| 2016 Septiembre | 146 | 11 | 157 |
| 2016 Agosto | 82 | 5 | 87 |
| 2016 Julio | 50 | 7 | 57 |
| 2016 Junio | 7 | 10 | 17 |
| 2016 Mayo | 5 | 2 | 7 |
| 2016 Abril | 4 | 4 | 8 |
| 2016 Marzo | 12 | 0 | 12 |
| 2016 Febrero | 8 | 2 | 10 |
| 2016 Enero | 5 | 1 | 6 |
| 2015 Diciembre | 5 | 0 | 5 |
| 2015 Noviembre | 10 | 2 | 12 |
| 2015 Octubre | 4 | 1 | 5 |
| 2015 Septiembre | 2 | 1 | 3 |
| 2015 Agosto | 4 | 3 | 7 |
| 2015 Julio | 57 | 3 | 60 |
| 2015 Junio | 37 | 6 | 43 |
| 2015 Mayo | 51 | 12 | 63 |
| 2015 Abril | 37 | 7 | 44 |
| 2015 Marzo | 67 | 4 | 71 |
| 2015 Febrero | 47 | 1 | 48 |
| 2015 Enero | 36 | 4 | 40 |
| 2014 Diciembre | 42 | 3 | 45 |
| 2014 Noviembre | 24 | 2 | 26 |
| 2014 Octubre | 37 | 5 | 42 |
| 2014 Septiembre | 37 | 0 | 37 |
| 2014 Agosto | 27 | 6 | 33 |
| 2014 Julio | 18 | 6 | 24 |
| 2014 Junio | 45 | 5 | 50 |
| 2014 Mayo | 37 | 6 | 43 |
| 2014 Abril | 26 | 4 | 30 |
| 2014 Marzo | 32 | 4 | 36 |
| 2014 Febrero | 28 | 3 | 31 |
| 2014 Enero | 25 | 5 | 30 |
| 2013 Diciembre | 30 | 6 | 36 |
| 2013 Noviembre | 0 | 1 | 1 |
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