e- Case Report
Mucocutaneous Manifestations of Infection by Histoplasma capsulatum in HIV-Negative Immunosuppressed Patients
Manifestaciones mucocutáneas de la infección por Histoplasma capsulatum en pacientes inmunosuprimidos
L.V. Gómez-Santanaa,
, A.C. Torrea, B.A. Hernándeza, V.I. Volonterib, B. Laurac, R. Luis-Galimbertia
Autor para correspondencia
a Servicio de Dermatología, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
b Servicio de Anatomía Patológica, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
c Servicio de Infectología, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Gómez-Santana, A.C. Torre, B.A. Hernández, V.I. Volonteri, B. Laura, R. Luis-Galimberti" "autores" => array:6 [ 0 => array:4 [ "nombre" => "L.V." "apellidos" => "Gómez-Santana" "email" => array:1 [ 0 => "leidy.gomez@hospitalitaliano.org.ar" ] "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" => "A.C." "apellidos" => "Torre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "B.A." "apellidos" => "Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "V.I." "apellidos" => "Volonteri" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "B." "apellidos" => "Laura" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "R." "apellidos" => "Luis-Galimberti" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Infectología, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manifestaciones mucocutáneas de la infección por <span class="elsevierStyleItalic">Histoplasma capsulatum</span> en pacientes inmunosuprimidos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1541 "Ancho" => 1750 "Tamanyo" => 667200 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A, Histiocytes and multinucleated Langhans giant cells in the dermis (hematoxylin-eosin, original magnification ×10). B, Multinucleated Langhans giant cells (hematoxylin-eosin, original magnification ×40). C, Multiple multinucleated giant cells (periodic acid-Schiff, original magnification ×40). D, Intrahistiocytic yeast-like structures (periodic acid-Schiff, original magnification ×100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Histoplasmosis is a systemic mycosis caused by the dimorphic fungus <span class="elsevierStyleItalic">Histoplasma capsulatum</span>, which enters the body upon inhalation of microconidia. Phagocytosis of these microconidia by alveolar macrophages transforms them into yeast-like structures, which are then disseminated in the bloodstream. Cell-mediated adaptive immunity promotes the activation of macrophages and the formation of epithelioid granulomas to control the infection.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2</span></a> This response is absent in immunocompromised patients, and the infection spreads to multiple organs. We describe 3 cases of <span class="elsevierStyleItalic">H capsulatum</span> infection in patients with compromised immunity unrelated to human immunodeficiency virus (HIV) infection. In all cases, diagnosis based on skin lesions was fundamental to allow early initiation of treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Case 1</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 54-year-old man reported fever, asthenia, dyspnea on moderate effort, and mucocutaneous lesions that had appeared 3 months earlier. The patient had an erythematous plaque with a tough, elastic-like consistency and diffuse borders that covered the nasal dorsum and left malar region, and on which sat a painful, rounded ulcer with a fibrinous base (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). On the patient's soft palate was an ulcer 2<span class="elsevierStyleHsp" style=""></span>cm in diameter with clearly defined borders and a granulomatous base (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The results of laboratory tests were as follows: hemoglobin, 14<span class="elsevierStyleHsp" style=""></span>g/dL; white blood-cell count, 5540/mm<span class="elsevierStyleSup">3</span>; CD4<span class="elsevierStyleSup">+</span> T-cell count, low (78 cells/L); platelet count, 234 900/mm<span class="elsevierStyleSup">3</span>. Liver and kidney function were normal, and the results of the tuberculin test, blood tests for HIV and hepatitis C and B, and the venereal disease research laboratory test were negative. The patient's protein profile was normal and the results of tests for antibodies (immunoglobulin M) against the Epstein-Barr virus, herpes 6 virus, cytomegalovirus, parvovirus B19, and human T-cell leukemia virus type 1 were negative. Computed tomography (CT) of the thorax, abdomen, and pelvis revealed a bilateral micronodular pulmonary infiltrate, mediastinal adenopathy, and bilateral adrenal gland hyperplasia. Direct microscopic examination of the lesions with Giemsa stain revealed intracytoplasmic yeast-like structures, with a predominantly polar staining pattern. Histology showed histiocytes and multinucleated Langhans giant cells in the dermis, with intrahistiocytic yeast-like structures. Skin cultures were positive for <span class="elsevierStyleItalic">H capsulatum</span>. The patient was treated with liposomal amphotericin (3<span class="elsevierStyleHsp" style=""></span>mg/kg/d) for 10 days. Continued outpatient treatment with itraconazole (400<span class="elsevierStyleHsp" style=""></span>mg/d) for 1 year resulted in resolution of the clinical signs. Serial blood tests ruled out HIV infection. Autoantibody analyses and serial blood tests revealed no immunological or hematological diseases. A diagnosis of idiopathic lymphopenia was established.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Case 2</span><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 57-year-old man who had undergone a heart transplant for dilated cardiomyopathy and was being treated with mycophenolate mofetil (2<span class="elsevierStyleHsp" style=""></span>g/d) and meprednisone (8<span class="elsevierStyleHsp" style=""></span>mg/d). He reported fever, weight loss, and cough that had appeared 15 days earlier. The patient had multiple painful erythematous nodules 1<span class="elsevierStyleHsp" style=""></span>cm in diameter on the lower limbs (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The results of serological tests for HIV and hepatitis B and C were negative. A chest CT scan revealed a cotton-like infiltrate in the middle lobe of the right lung. <span class="elsevierStyleItalic">H capsulatum</span> was detected by histology and culture. The clinical signs resolved after 1 year of treatment with itraconazole (400<span class="elsevierStyleHsp" style=""></span>mg/d). Bimonthly check-ups were scheduled.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Case 3</span><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was a 75-year-old man who had undergone a liver transplant for primary sclerosing cholangitis and was being treated with methylprednisone (4<span class="elsevierStyleHsp" style=""></span>mg/d), tacrolimus (3<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h), and mycophenolic acid (360<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h). He complained of fever and sensory deterioration. Multiple rounded purpuric papules with central umbilication ranging in size from 2<span class="elsevierStyleHsp" style=""></span>mm to 4<span class="elsevierStyleHsp" style=""></span>mm were located on the face, abdomen, and limbs (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Chest CT showed a bilateral micronodular pulmonary infiltrate. Brain CT and cerebrospinal fluid analysis revealed no findings of note. The results of serological tests for HIV and hepatitis B and C were negative. The presence of <span class="elsevierStyleItalic">H capsulatum</span> was demonstrated by direct smear using Giemsa stain as well as culture and skin histopathology (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). Treatment with liposomal amphotericin (5<span class="elsevierStyleHsp" style=""></span>mg/kg/d) was initiated. However, 4 days later multiple organ failure developed and the patient died.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Comments</span><p id="par0025" class="elsevierStylePara elsevierViewall">Two varieties of <span class="elsevierStyleItalic">H capsulatum</span> (var. <span class="elsevierStyleItalic">duboisii</span> and var. <span class="elsevierStyleItalic">capsulatum</span>, found in Africa and the Americas, respectively) are pathogenic to humans, and histoplasmosis is the most prevalent mycosis in endemic countries.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a> Several cases reported in the United States and Latin America have highlighted the presence of disseminated infections in immunocompromised patients, 70% to 90% of whom had HIV infection.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,5</span></a> Cases have been reported in countries in Africa, Asia, and Europe, and histoplasmosis is therefore considered a globally distributed infection.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the majority of cases, primary exposure to <span class="elsevierStyleItalic">H capsulatum</span> results in a nonsymptomatic infection or causes nonspecific symptoms and resolves without need for treatment.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2–7</span></a> Disseminated histoplasmosis occurs in patients with impaired cell-mediated immunity, such as HIV-positive patients with a CD4<span class="elsevierStyleSup">+</span> count of less than 100 cells/μL,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> patients with oncohematological diseases, recipients of solid organ or hematopoietic cell transplants, patients treated with immunosuppressants or tumor necrosis factor antagonists, and those with congenital T-cell deficiencies.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,6</span></a> Two of the patients we have described had been treated with immunosuppressants after undergoing solid organ transplantation, and one was diagnosed with idiopathic CD4<span class="elsevierStyleSup">+</span> lymphopenia after other infectious and neoplastic diseases were ruled out as possible causes of immunodeficiency.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Clinical signs of disseminated disease include constitutional symptoms, organomegaly, generalized lymphadenopathy, lung and/or liver disease, and bone marrow and adrenal gland deficiencies. Central nervous system compromise is observed in 5% to 10% of patients.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3,8</span></a> In Latin America, cutaneous involvement is observed in 38% to 85% of histoplasmosis patients with AIDS, as compared with 10% to 25% in the rest of the world. This higher frequency in Latin America is thought to be due to the presence of different phylogenetic species of <span class="elsevierStyleItalic">H capsulatum</span> (classes 5 and 6) in the region.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,9</span></a> Skin lesions can be primary, resulting from direct inoculation of the fungus into the skin (although this is very rare), or secondary to hematogenous spread of the fungus. Lesions are characterized by marked polymorphism and can manifest as papules, plaques, pustules, nodules, erosions, or molluscoid or acneiform lesions.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3,10</span></a> The most common mucosal lesions are granulomatous ulcers located on the tongue, palate, and buccal and gingival mucosa, and less frequently on the larynx and the penis.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,9,10</span></a> The first of our patients presented with ulcerated granulomatous lesions, while the other 2 patients had multiple, disseminated nodular and molluscoid lesions.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis is established by direct microscopy using Giemsa or silver methenamine stains, serum antigen detection, and detection of specific antibodies by enzyme-linked immunosorbent assay.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Isolation of the fungus in tissue culture is the gold standard for diagnosis, but requires the use of facilities and practices corresponding to biosafety level 3.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,12</span></a> Histology reveals the presence of multinucleated giant cells and granulomas with or without caseating necrosis, and the presence inside macrophages of yeast-like structures, which can be visualized using periodic acid-Schiff, methenamine silver, or Gomori-Grocott staining. The epicutaneous histoplasmin test is used for epidemiological studies but is not useful for diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6,9</span></a> Another diagnostic method is the detection of DNA by polymerase chain reaction techniques, which have a diagnostic sensitivity and specificity close to 90% and are useful in severely immunocompromised patients.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,12</span></a> In the 3 cases presented here, <span class="elsevierStyleItalic">H capsulatum</span> was isolated from skin cultures.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Liposomal amphotericin B is the drug of choice for initial treatment in patients with systemic compromise.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> For oral treatment, azo compounds are used. Currently, itraconazole is the treatment of choice. It is administered at 400<span class="elsevierStyleHsp" style=""></span>mg/d for at least a year. To reduce the risk of relapse, its blood concentration should be measured periodically until levels reach 1 to 2<span class="elsevierStyleHsp" style=""></span>μg/mL.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,14</span></a> Other recently developed triazoles, such as voriconazole and isavuconazole, have shown in vitro activity against <span class="elsevierStyleItalic">H capsulatum</span> similar to that of itraconazole. However, owing to their frequent interactions with other drugs administered long term, triazoles are reserved for the small number of patients with disseminated histoplasmosis who cannot tolerate other treatments.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">13,15</span></a> Further studies are required to demonstrate their advantages over other currently used drugs.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Histoplasmosis is a systemic mycosis that should be included in the differential diagnosis of comparable skin lesions, even in nonendemic countries given today's high levels of migration. It is necessary to fully review the patient's clinical history, in which all recent trips and activities should be recorded, in order to establish a diagnosis and initiate appropriate and timely treatment. This is especially important in immunocompromised patients.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1022287" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec980449" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1022286" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec980450" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Case 2" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Case 3" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Comments" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "Références" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec980449" "palabras" => array:4 [ 0 => "Disseminated histoplasmosis" 1 => "Cutaneous histoplasmosis" 2 => "Immunosuppression" 3 => "Itraconazole" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec980450" "palabras" => array:4 [ 0 => "Histoplasmosis diseminada" 1 => "Histoplasmosis cutánea" 2 => "Inmunosupresión" 3 => "Itraconazol" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Histoplasmosis is a systemic mycosis caused by the dimorphous fungus <span class="elsevierStyleItalic">Histoplasma capsulatum (H. capsulatum)</span>. The fungus enters the body through the respiratory tract in the form of microconidia, which are transformed into intracellular yeast-like structures in the lungs before disseminating hematogenously. Primary infection is usually asymptomatic and self-resolving. Some patients develop severe disease with acute or chronic respiratory involvement. Immunosuppressed patients, mainly those with altered cellular immunity, may have disseminated disease with variable mucocutaneous involvement characterized by papules, nodules, gummas, or ulcers with a granulomatous base. We report the case of 3 HIV-negative patients infected by <span class="elsevierStyleItalic">H capsulatum</span> in whom diagnosis based on the skin lesions proved essential for early initiation of treatment.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La histoplasmosis es una micosis sistémica causada por el hongo dimorfo <span class="elsevierStyleItalic">Histoplasma capsulatum (H. capsulatum).</span> Este entra en el organismo a través del tracto respiratorio en forma de microconidias, que a nivel pulmonar se transforman en elementos levaduriformes intracelulares, y luego se diseminan por vía hematógena. La primoinfección suele ser asintomática y autorresolutiva. Algunos pacientes desarrollan una enfermedad grave con compromiso respiratorio agudo o crónico. Los pacientes inmunosuprimidos, principalmente aquellos con alteración de la inmunidad celular, pueden presentar una enfermedad diseminada con compromiso mucocutáneo proteiforme, con pápulas, nódulos, gomas o úlceras de fondo granulomatoso. Se comunican 3 casos clínicos de pacientes inmunosuprimidos no VIH, con infección por <span class="elsevierStyleItalic">H. capsulatum</span>, en quienes el diagnóstico a partir de las lesiones cutáneas resultó fundamental para el inicio precoz del tratamiento.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gómez-Santana LV, Torre AC, Hernández BA, Volonteri VI, Laura B, Luis-Galimberti R. Manifestaciones mucocutáneas de la infección por <span class="elsevierStyleItalic">Histoplasma capsulatum</span> en pacientes inmunosuprimidos. Actas Dermosifiliogr. 2018;109:e27–e32.</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" => 975 "Ancho" => 1300 "Tamanyo" => 236009 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Hard, elastic, erythematous plaque with diffuse borders located on the nasal dorsum and the left malar region. Overlying this lesion is a rounded ulcer 5<span class="elsevierStyleHsp" style=""></span>mm in diameter with a completely fibrinous base.</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" => 1219 "Ancho" => 1625 "Tamanyo" => 205400 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Rounded ulcer 2<span class="elsevierStyleHsp" style=""></span>cm in diameter on the soft palate. The ulcer has well defined borders and a granulomatous base.</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" => 1219 "Ancho" => 1625 "Tamanyo" => 166805 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Multiple painful erythematous nodules 1<span class="elsevierStyleHsp" style=""></span>cm in diameter located on the lower limbs.</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" => 2309 "Ancho" => 1750 "Tamanyo" => 466123 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Multiple rounded purpuric papules with central umbilication, ranging in size from 2<span class="elsevierStyleHsp" style=""></span>mm to 4<span class="elsevierStyleHsp" style=""></span>mm, located on the face (A and B) and the limbs (C).</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1541 "Ancho" => 1750 "Tamanyo" => 667200 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A, Histiocytes and multinucleated Langhans giant cells in the dermis (hematoxylin-eosin, original magnification ×10). B, Multinucleated Langhans giant cells (hematoxylin-eosin, original magnification ×40). C, Multiple multinucleated giant cells (periodic acid-Schiff, original magnification ×40). D, Intrahistiocytic yeast-like structures (periodic acid-Schiff, original magnification ×100).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "Références" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Manifestaciones cutáneo-mucosas de la histoplasmosis diseminada (histoplasmosis clásica o histoplasmosis capsulati" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Negroni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Dermatol Argent." 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 10 | 7 | 17 |
| 2024 Octubre | 74 | 46 | 120 |
| 2024 Septiembre | 117 | 19 | 136 |
| 2024 Agosto | 125 | 66 | 191 |
| 2024 Julio | 100 | 27 | 127 |
| 2024 Junio | 123 | 34 | 157 |
| 2024 Mayo | 71 | 38 | 109 |
| 2024 Abril | 88 | 30 | 118 |
| 2024 Marzo | 109 | 30 | 139 |
| 2024 Febrero | 102 | 47 | 149 |
| 2024 Enero | 79 | 29 | 108 |
| 2023 Diciembre | 83 | 13 | 96 |
| 2023 Noviembre | 98 | 24 | 122 |
| 2023 Octubre | 79 | 22 | 101 |
| 2023 Septiembre | 93 | 45 | 138 |
| 2023 Agosto | 74 | 24 | 98 |
| 2023 Julio | 115 | 37 | 152 |
| 2023 Junio | 90 | 26 | 116 |
| 2023 Mayo | 98 | 29 | 127 |
| 2023 Abril | 98 | 21 | 119 |
| 2023 Marzo | 98 | 36 | 134 |
| 2023 Febrero | 62 | 24 | 86 |
| 2023 Enero | 63 | 29 | 92 |
| 2022 Diciembre | 86 | 45 | 131 |
| 2022 Noviembre | 30 | 27 | 57 |
| 2022 Octubre | 36 | 24 | 60 |
| 2022 Septiembre | 53 | 43 | 96 |
| 2022 Agosto | 34 | 35 | 69 |
| 2022 Julio | 27 | 43 | 70 |
| 2022 Junio | 21 | 34 | 55 |
| 2022 Mayo | 63 | 39 | 102 |
| 2022 Abril | 70 | 37 | 107 |
| 2022 Marzo | 77 | 50 | 127 |
| 2022 Febrero | 59 | 43 | 102 |
| 2022 Enero | 46 | 54 | 100 |
| 2021 Diciembre | 41 | 43 | 84 |
| 2021 Noviembre | 58 | 45 | 103 |
| 2021 Octubre | 57 | 64 | 121 |
| 2021 Septiembre | 36 | 52 | 88 |
| 2021 Agosto | 45 | 62 | 107 |
| 2021 Julio | 58 | 43 | 101 |
| 2021 Junio | 47 | 47 | 94 |
| 2021 Mayo | 43 | 50 | 93 |
| 2021 Abril | 138 | 88 | 226 |
| 2021 Marzo | 92 | 41 | 133 |
| 2021 Febrero | 89 | 47 | 136 |
| 2021 Enero | 48 | 49 | 97 |
| 2020 Diciembre | 50 | 42 | 92 |
| 2020 Noviembre | 52 | 47 | 99 |
| 2020 Octubre | 34 | 24 | 58 |
| 2020 Septiembre | 49 | 23 | 72 |
| 2020 Agosto | 46 | 30 | 76 |
| 2020 Julio | 32 | 37 | 69 |
| 2020 Junio | 48 | 45 | 93 |
| 2020 Mayo | 33 | 13 | 46 |
| 2020 Abril | 21 | 19 | 40 |
| 2020 Marzo | 22 | 17 | 39 |
| 2020 Febrero | 2 | 0 | 2 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 10 | 0 | 10 |
| 2019 Agosto | 2 | 0 | 2 |
| 2019 Julio | 6 | 0 | 6 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 1 | 7 |
| 2019 Abril | 4 | 0 | 4 |
| 2019 Marzo | 2 | 0 | 2 |
| 2019 Febrero | 4 | 0 | 4 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 3 | 0 | 3 |
| 2018 Septiembre | 3 | 0 | 3 |
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