Paracoccidioidomycosis manifested by sarcoid-like cutaneous lesions with severe systemic disease: a rare and challenging diagnosis

ABSTRACT Cutaneous involvement in paracoccidioidomycosis (PCM) can exhibit a highly polymorphic spectrum. The infiltrative pattern corresponds to up to 26.6% of observed skin lesions, including sarcoid-like plaques, a rare presentation of cutaneous lesions in PCM. This clinical expression is almost exclusively cutaneous, and its histology reveals a tuberculoid granuloma with a scarcity of fungi, leading to misdiagnosis as other granulomatous diseases. Here, we report a rare form of chronic multifocal paracoccidioidomycosis manifesting as sarcoid-like skin lesions misdiagnosed as granulomatous rosacea in a patient with severe systemic disease.

Paracoccidoidomicosis: Reporte de 4 casos

La paracoccidioidomicosis (PCM) es una infección causada por hongos patógenos humanos del género Paracoccidioides. Es una micosis sistémica que puede afectar cualquier órgano. Se describen con este reporte cuatro casos de paracoccidioidomicosis con diferentes presentaciones clínicas, tiempo de evolución, con afectación mucocutánea, pulmonar, glándulas suprarrenales, sistema nervioso entre otros, principalmente en adultos varones de diferentes edades y profesiones, tanto inmunosuprimidos como inmunocompetentes, teniendo en común el contacto con el suelo. Se demuestra de esta manera la importancia de considerar esta patología ante una sospecha clínica de micosis sistémica para así realizar una confirmación temprana y tratamiento oportuno ya que presenta buena respuesta terapéutica antimicótica y mejoría clínica.

Paracoccidioidomycosis (PCM) is an infection caused by human pathogenic fungi of the genus Paracoccidioides. This report describes: 4 cases of paracoccidioidomycosis diagnosed with different clinical presentations, different times of evolution, with mucocutaneous, pulmonary, adrenal gland, and nervous system involvement, among others, mainly in male adults of different ages and professions, both immunosuppressed and immunocompetent, having in common contact with the ground. In this way, PCM is a systemic mycosis that can affect any organ and therefore the importance of considering this pathology when a diagnostic suspicion of systemic mycosis is presented in order to make an early diagnosis and timely treatment since it presents a good therapeutic response, antifungal and clinical improvement.

Tendência da mortalidade por Paracoccidioidomicose no Brasil ­ 1996 a 2020 / Mortality trends due to Paracoccidioidomycosis in Brazil ­ 1996 to 2020

Objetivo: Analisar a tendência da mortalidade por paracoccidioidomicose (PCM) e caracterizar o perfil sociodemográfico no Brasil e suas regiões geográficas numa série temporal de 25 anos. Métodos: Trata-se de estudo ecológico de séries temporais. Considerou-se como participantes do estudo a população brasileira dividida em faixas etárias, que tiveram como causa básica do óbito a PCM. Para calcular a variação percentual anual (VPA) dos coeficientes, na análise de tendência, foi utilizada a regressão de Prais-Winsten. Os coeficientes de mortalidade foram calculados a nível nacional, segundo as regiões geográficas, sexo e faixa etária e proporcional para as demais variáveis. Resultados: De acordo com os resultados deste estudo, ocorreram 2.101 óbitos por PCM no Brasil. A tendência ao longo dos 25 anos evidenciou um comportamento estável nas regiões Norte e Nordeste. Já no Sul, Sudeste e Centro-Oeste houve uma tendêndia de queda. A mortalidade média no Brasil foi de 84,04/100 mil hab., VPA -3,29 (IC 95% -2,43; -4,14). Levando em consideração a análise dos aspectos sociodemográficos, houve um predomínio de escolaridade ignorada (764; 36%), raça/ cor da pele branca (1.109; 53%), estado civil misto: casado (942; 45%) e solteiro (640; 30%), local de ocorrência do óbito predominantemente no âmbito hospitalar (1.852; 88%). Conclusão: Tanto no Brasil como nas regiões geográficas Sudeste, Sul e Centro-Oeste a mortalidade por PCM apresentou-se com tendência temporal decrescente. Já nas regiões Nordeste e Norte a tendência foi estacionária. O perfil sociodemográfico dos pacientes que foram a óbito apontou para sexo masculino, adultos, de baixa escolaridade, brancos e casados.

Objective: To analyze the trend in mortality from paracoccidioidomycosis (PCM) and characterize the sociodemographic profile in Brazil and its geographic regions in a 25-year time series. Methods: This is an ecological time series study. The study participants were the Brazilian population divided into age groups whose underlying cause of death was PCM. To calculate the annual percentage change (VPA) of the coefficients in the trend analysis, the Prais-Winsten regression was used. National mortality coefficients were calculated according to geographic regions, sex and age group and proportional to the other variables. Results: According to this study, there were 2,101 deaths from PCM in Brazil. The trend over the 25 years showed stable behavior in the North and Northeast regions. In the South, Southeast, and Midwest, there was a downward trend. The average mortality in Brazil was 84.04/100,000 inhab., VPA -3.29 (95% CI -2.43; -4.14). According to the analysis of sociodemographic aspects, there was a predominance of ignored schooling (764 deaths; 36%), white race/skin color (1,109; 53%), mixed marital status: married (942; 45%) and single (640; 30%), and place of death predominantly in the hospital environment (1,852; 88%). Conclusion: In Brazil and in the Southeast, South, andMidwest geographic regions, mortality from PCM showed a decreasing temporal trend. In the Northeast and North regions, the trend was stationary. The sociodemographic profile of the dying patients indicated males, adults, with low education, white, and married.

Diagnóstico micológico de paracoccidioidomicosis en un hospital de área no endémica: metodología clásica y molecular

Introducción. La paracoccidioidomicosis es una micosis sistémica y endémica en Latinoamérica. El cambio climático y el movimiento migratorio del huésped enfatizan la necesidad de optimizar el diagnóstico de esta infección. Objetivo. Evaluar la implementación de la detección de ADN de Paracoccidioides spp. al diagnóstico micológico de pacientes con sospecha de paracoccidioidomicosis. Materiales y métodos. Estudio retrospectivo con datos de laboratorio de pacientes con sospecha de paracoccidioidomicosis en un hospital de área no endémica. Resultados. Se analizaron los resultados de las muestras de 19 pacientes con sospecha clínica de paracoccidioidomicosis. El 90 % de los pacientes había nacido o visitado un área endémica de esta micosis en Latinoamérica. En 14 pacientes varones adultos se confirmó paracoccidioidomicosis por diagnóstico convencional. El examen directo fue positivo en 12 pacientes con enfermedad comprobada y en 4 de ellos se obtuvo crecimiento del hongo. Se detectaron anticuerpos contra Paracoccidioides spp. en ocho pacientes con la enfermedad. Se realizó PCR anidada con muestras de 14 pacientes para detectar ADN de Paracoccidioides spp. En 9 de los 10 pacientes con diagnóstico convencional de paracoccidioidomicosis se obtuvo una prueba de PCR positiva. Conclusiones. La implementación de técnicas moleculares para detectar ADN de Paracoccidioides spp. complementa el diagnóstico convencional de paracoccidioidomicosis y permite instaurar el tratamiento antifúngico, sobre todo en los casos clínicos donde no se observa la presencia del hongo en las muestras clínicas. La migración actual de poblaciones humanas dificulta el diagnóstico de paracoccidioidiomicosis y otras infecciones endémicas, por lo que se requiere optimizar el diagnostico micológico en los laboratorios clínicos para tratar pacientes con este tipo micosis desatendida.

Introduction. Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis. Objective. To evaluate the implementation of Paracoccidioides spp. DNA detection in the mycological diagnosis of patients with suspected paracoccidioidomycosis. Materials and methods. It is a retrospective study with laboratory data from patients with clinical suspicion of paracoccidioidomycosis, who consulted a university hospital from a non-endemic area. Results. We analyzed the laboratory results of samples from 19 patients with suspected paracoccidioidomycosis. Seventeen out of 19 patients were born in or had visited an endemic area in Latin America. Fourteen adult male patients were confirmed to have paracoccidioidomycosis by conventional diagnosis: the direct examination was positive in 12 samples while fungal growth was found only in 4. Anti-Paracoccidioides spp. antibodies were detected in 10 patients, 8 of them with proven paracoccidioidomycosis. Nested PCR for Paracoccidioides spp. detection was performed on clinical samples from 14 patients, and positive results were obtained for 9 out of 10 patients with the conventional diagnosis of paracoccidioidomycosis. Conclusions. The incorporation of molecular techniques to detect Paracoccidioides spp. DNA complements the conventional diagnosis of paracoccidioidomycosis. This tool allows the prescription of antifungal treatment in those cases where the fungus is not observed in the clinical samples. Current human migrations difficult the mycological diagnosis of paracoccidioidomycosis and other fungal infections. For this reason, it is necessary to improve mycological diagnosis in clinical laboratories to adequately treat patients with this neglected mycosis.

Fast and cost-effective protocol to produce Paracoccidioides spp. antigens

Introduction. The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility. Objective. To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis. Materials and methods. The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after 5, 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors. Results. Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time. Conclusion. The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.

Introducción. Los métodos existentes para la producción de los antígenos de Paracoccidioides spp. son problemáticos en su estandarización, especificidad, estabilidad, repetibilidad y reproducibilidad. Objetivo. Optimizar la metodología para la producción de antígenos de Paracoccidioides spp. y evaluar su aplicabilidad en el inmunodiagnóstico de la paracoccidioidomicosis. Materiales y métodos. Los antígenos se obtuvieron de aislamientos de P. lutzii (01, 66 y 8334), P. brasiliensis sensu stricto (113) y P. restripiensis (B-339). Estos hongos se cultivaron a 36 °C ± 1 °C en agar Fava-Netto modificado, según Freitas et al. (2018). Los antígenos de P. lutzii se obtuvieron a los 5, 10 y 20 días de cultivo y los antígenos de P. brasiliensis y P. restripiensis se obtuvieron a los 10 días. Los antígenos se evaluaron in natura, concentrados 10 y 20 veces. La capacidad antigénica se evaluó mediante un ensayo de inmunodifusión doble con muestras de suero de pacientes con paracoccidioidomicosis, histoplasmosis, aspergilosis y donantes de sangre aleatorios. Resultados. Se observó reacción cruzada con Paracoccidioides spp. cuando se evaluaron los antígenos de P. brasiliensis, P. restrepiensis y P. lutzii frente a los anticuerpos policlonales contra P. lutzii y P. brasiliensis, respectivamente. No hubo reactividad cruzada con los anticuerpos policlonales contra Histoplasma capsulatum y Aspergillus fumigatus, ni contra los donantes de sangre aleatorios. El protocolo propuesto permitió la producción estable, repetible y reproducible de antígenos dirigidos de un género específico (Paracoccidiodes) en un tiempo corto de cultivo y a un menor costo. Conclusión. El protocolo propuesto permitió obtener antígenos específicos de un género, que pueden ser desarrollados y reproducidos en todos los laboratorios de Antígenos de Paracoccidioides spp.: protocolo rápido Brasil y Surámerica donde la paracoccidioidomicosis es una enfermedad endémica y desatendida. Estos antígenos pueden contribuir al diagnóstico precoz de la infección, independientemente de la especie.

Hiperplasia pseudoepiteliomatosa: carcinoma escamocelular versus paracoccidioidomicosis oral, un caso con mirada dermatológica / Pseudoepitheliomatous hyperplasia: Squamous cell carcinoma versus oral paracoccidioidomycosis, a case from a dermatological perspective

La paracoccidioidomicosis es una micosis sistémica endémica en Latinoamérica. La presentación más frecuente compromete crónicamente los pulmones, la piel y las mucosas. Al inicio, este paciente presentó, por varios años, una lesión única en la mucosa oral que, en ausencia de otros síntomas, se relacionó con una neoplasia maligna, específicamente con un carcinoma escamocelular. La diferenciación entre los dos diagnósticos se hace mediante un examen directo, un estudio histopatológico y cultivos iniciales y subsecuentes. Sin embargo, tales estudios no fueron concluyentes. Después de varias consultas y pruebas, con los resultados del examen directo, la inmunodifusión y la PCR en tiempo real se confirmó el diagnóstico de paracoccidioidomicosis crónica multifocal. Este caso alerta sobre la ausencia de sospecha clínica de micosis endémicas, dada la presencia de lesiones mucocutaneas que pueden ser producidas por hongos como Paracoccidioides spp, y la importancia de considerarlas entre los diagnósticos diferenciales.

Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. The most frequent form involves a chronic compromise of the lungs, skin, and mucosa. The patient started with a single oral lesion that lasted for several years. The absence of other symptoms pointed out a possible malignant neoplasm, specifically a squamous cell carcinoma. Differentiation between both diagnoses-fungal infection and carcinoma-depends on the results of the direct examination, the histopathological study, and the initial and subsequent cultures. However, in this case, those findings were not conclusive. The coexistence of both diagnoses is frequent and increases the diagnostic challenge. After several consultations and tests, direct examination, immunodiffusion and real-time PCR findings the multifocal chronic paracoccidioidomycosis diagnosis was confirmed. This case warns about a systematical absence of clinical suspicion of endemic mycoses before the appereance of mucocutaneous lesions, which can be produced by fungi like Paracoccidioides spp, and the importance of considering those mycoses among the differential diagnoses.

Paraccocidiomicosis sistémica en consumidor crónico de corticoides

La Paracoccidiomicosis es una infección endémica. Junto con la histoplasmosis, son las infecciones micóticas más frecuentes en Latinoamérica. Esta micosis puede ser de afección local o sistémica, con un marcado trofismo por los pulmones, órganos linfoides, hígado, glándulas suprarrenales, piel y mucosa. Presentamos el caso de un varón adulto, consumidor crónico de corticoides, que desarrolla una paracoccidiomicosis sistémica con afección pulmonar y de glándulas suprarrenales con buena repuesta a la terapéutica antifúngica.

Paracoccidiomycosis is an endemic infection, together with histoplasmosis, they are the most frequent fungal infections in Latin America. This mycosis can be of local or systemic affection, with a marked trophism by the lungs, lymphoid organs, liver, adrenal glands, skin and mucosa. We present the case of an adult male, chronic steroid user, who develops systemic paracoccidiomycosis with pulmonary and adrenal gland involvement with good response to antifungal therapy.

"Star of Bethlehem sign" in the analysis of the evolution of brain lesions during and after treatment for neuroparacoccidioidomycosis / "Sinal da Estrela de Belém" na análise evolutiva das lesões durante e após o tratamento em pacientes com neuroparacoccidioidomicose

Abstract Objective: To describe the clinical and radiological evolution of lesions during and after treatment in patients diagnosed with neuroparacoccidioidomycosis (NPCM). Materials and Methods: This was a retrospective study of the medical records, computed tomography scans, and magnetic resonance imaging (MRI) scans of patients with NPCM treated between September 2013 and January 2022. Results: Of 36 cases of NPCM, eight were included in the study. One patient presented only with pachymeningeal and skull involvement, and seven presented with pseudotumors in the brain. Collectively, the eight patients presented with 52 lesions, of which 46 (88.5%) were supratentorial. There were 32 lesions with a diameter ≤ 1.2 cm, of which 27 (84.4%) disappeared during the treatment. In three cases, there were lesions > 1.2 cm that showed a characteristic pattern of evolution on MRI: an eccentric gadolinium contrast-enhanced nodule, with a subsequent decreased in the size and degree of contrast enhancement of the lesions. Conclusion: In NPCM, supratentorial lesions seem to predominate. Lesions ≤ 1.2 cm tend to disappear completely during treatment. Lesions > 1.2 cm tend to present with a similar pattern, designated the "Star of Bethlehem sign", throughout treatment.

Resumo Objetivo: Descrever a evolução clínica e radiológica das lesões durante e após o tratamento de pacientes diagnosticados com neuroparacoccidioidomicose (NPCM). Materiais e Métodos: Revisamos os prontuários médicos, estudos de tomografia computadorizada e ressonância magnética (RM) de pacientes com NPCM de nossa instituição, no período de setembro de 2013 a janeiro de 2022. Resultados: Dos 36 casos de NPCM, oito foram incluídos no presente estudo. Um caso apresentava apenas envolvimento paquimeníngeo e ósseo craniano e sete casos apresentavam lesões encefálicas pseudotumorais, totalizando 52 lesões, sendo 46 (88,5%) supratentoriais. Dentre 32 lesões com diâmetro ≤ 1,2 cm, 27 (84,4%) apresentaram resolução completa durante o tratamento. Três casos apresentaram padrão semelhante de evolução da lesão na RM em lesões > 1,2 cm, caracterizado pelo aparecimento de nódulo excêntrico com impregnação pelo gadolínio, seguido de redução das dimensões e do realce nodular pelo contraste nos estudos subsequentes. Conclusão: A NPCM apresenta-se predominantemente com lesões supratentoriais. Lesões ≤ 1,2 cm tendem a desaparecer completamente durante o tratamento. Lesões > 1,2 cm tendem a apresentar um padrão de imagem de RM característico ao longo do tratamento, descrito como o "sinal da Estrela de Belém".

Paraccoicidiomicosis, reflexión de una micosis diseminada: reporte de caso

Introducción: La paracoccidioidomicosis, es una micosis endémica en diferentes países de latinoamérica, incluyendo zonas de Colombia, con manifestación clínica muy variada ya que es considerada una enfermedad que puede ser crónica y sistémica. Objetivos: Exponer la importancia del examen clínico-estomatológico en la detección de diferentes entidades en sistema estomatognático, y el manejo multidisciplinario de paracoccidioidomicosis oral y sistémica. Caso clínico: paciente masculino en sexta década de vida, el cual presenta glosalgia y dolor de región ocular. Clínicamente presenta lesión de tipo granulomatoso en bordes laterales de lengua con evolución de hace 1 año aproximadamente, el resultado de la biopsia es paracoccidioidomicosis, se inicia manejo multidisciplinario con medicamentos intravenosos y orales, luego de 10 meses presenta resolución de este. Conclusiones: un buen interrogatorio, análisis de cuadro clínico y exámenes complementarios, son claves para un diagnóstico temprano y tratamiento oportuno, preservando la vida del paciente, especialmente en infecciones oportunistas como la paracoccidioidomicosis.

Introdução: A paracoccidioidomicose é uma micose endêmica em diferentes países da América Latina, incluindo áreas da Colômbia, com manifestação clínica muito variada por ser considerada uma doença que pode ser crônica e sistêmica. Objetivos: Expor a importância do exame clínico-estomatológico na detecção de diferentes entidades do sistema estomatognático e no manejo multidisciplinar da paracoccidioidomicose oral e sistêmica. Caso clínico: paciente do sexo masculino na sexta década de vida, que apresentava glossalgia e dor na região ocular. Clinicamente apresenta lesão tipo granulomatosa nas bordas laterais da língua com evolução de aproximadamente 1 ano, resultado da biópsia é paracoccidioidomicose, inicia-se manejo multidisciplinar com medicações endovenosas e orais, após 10 meses resolve. Conclusões: um bom questionamento, análise do quadro clínico e exames complementares são fundamentais para o diagnóstico precoce e tratamento oportuno, preservando a vida do paciente, principalmente nas infecções oportunistas como a paracoccidioidomicose.

Introduction: Paracoccidioidomycosis is an endemic mycosis in different Latin American countries, including areas of Colombia, with a very varied clinical manifestation since it is considered a disease that can be chronic and systemic. Objectives: To expose the importance of the clinical-stomatological examination in the detection of different entities in the stomatognathic system, and the multidisciplinary management of oral and systemic paracoccidioidomycosis. Clinical case: male patient in the sixth decade of life, who presented glossalgia and pain in the ocular region. Clinically, it presents a granulomatous-type lesion on the lateral edges of the tongue with evolution of approximately 1 year ago, the result of the biopsy is paracoccidioidomycosis, multidisciplinary management is started with intravenous and oral medications, after 10 months it resolves. Conclusions: a good questioning, analysis of the clinical picture and complementary tests are key to early diagnosis and timely treatment, preserving the patient's life, especially in opportunistic infections such as paracoccidioidomycosis.

Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis

ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

Chylothorax and chylous ascites due to juvenile paracoccidioidomycosis: a case report

ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.

Chronic disseminated paracoccidioidomycosis: the first case reported in China / 中华皮肤科杂志

To report the first case of chronic disseminated paracoccidioidomycosis in China. A 49-year-old male patient presented with papules and nodules of the skin for 1 year, and papules and ulcers on the oral mucosa for 2 months. Skin examination showed the edema of the left foot, multiple crusting ulcers on the sole of the left foot, ulcers with a granular base in the interdigital regions between the third and fourth toes as well as fourth and fifth toes of the left foot, accompanied by punctate hemorrhage and exudation; there were multiple papules, nodules, and plaques on the dorsum and medial side of the left foot and the left knee, with ulcers and crusts in the center; 2 papules were observed on the left wrist, and 1 papule on the left upper lip with a crusted surface; red plaques with ulcers and punctate hemorrhage were observed on the gingival mucosa, buccal mucosa, labial mucosa, and palate, and the lesions mainly occurred on the left side. Ultrasonography of superficial lymph nodes showed bilateral cervical and supraclavicular lymph node enlargement, which was more obvious on the left side. Computed tomography of the chest and abdomen showed diffuse miliary nodular shadows, and cordlike, cloudy flocculent and nodular high-density shadows in both lungs, as well as obvious thickening of the left adrenal gland in the abdomen. Yeast cells were observed by immunofluorescent staining of biopsy tissues from the oral mucosa and left lower limb. Histopathological examination of biopsy tissues from the oral mucosa and left lower limb showed granulomatous inflammation, and refractive double-membrane yeast cells could be observed inside or outside the multinucleated giant cells, without or with a single bud or multiple buds; periodic acid-Schiff staining and hexamine silver staining of the above biopsy tissues were positive. Fungal culture of the left lower limb lesion in Sabouraud dextrose agar medium at 25℃ and 37℃ both yielded fungal hyphae. Metagenomics sequencing of the oral mucosal tissue and alveolar lavage fluid indicated the infection with Paracoccidioides brasiliensis. The diagnosis of chronic disseminated paracoccidioidomycosis was confirmed. After 1-month oral treatment with itraconazole capsules at a dose of 400 mg/d, the lesions on the skin and oral mucosa markedly improved, and computed tomography imaging of the lung and left adrenal gland also showed obvious improvement. The dose of itraconazole was reduced to 200 mg/d after 3 months. The patient′s condition further improved during a 10-month follow-up.

Reporte de dos casos de neuro-paracoccidiomicosis / Report of two cases of neuro-paracoccidiomycosis

La paracoccidiodomicosis es la micosis sistémica más frecuente en América Latina. La afectación del sistema nervioso central (SNC) está descrita en un 10-27%. El objetivo es presentar dos pacientes del sexo masculino con neuroparacoccidiodomicosis internados en el Departamento de Medicina Interna del Hospital Nacional, uno en el año 2017 y el otro en el 2021. Ambos pacientes presentaron síntomas neurológicos con mejoría de las lesiones con anfotericina B. Los granulomas cerebrales de PCM pueden tener comportamiento pseudotumoral. La regresión de las lesiones fue completa con anfotericina B y trimetoprin sulfametoxasol en el primer caso y anfotericina B e itraconazol en el segundo caso.

Paracoccidioidomycosis is the most common systemic mycosis in Latin America. Central nervous system (CNS) involvement is described in 10-27%. The objective is to present two male patients with neuroparacoccidioidomycosis admitted to the Department of Internal Medicine of the National Hospital, one in 2017 and the other in 2021. Both patients presented neurological symptoms with improvement of the lesions with amphotericin B. The granulomas brain cells of PCM may have pseudotumor behavior. Regression of the lesions was complete with amphotericin B and trimethoprim sulfamethoxazole in the first case and amphotericin B and itraconazole in the second case.

Paracoccidioidomycosis with digestive manifestations in a pediatric patient / Paracoccidioidomicosis con manifestaciones digestivas en un paciente pediátrico

Abstract Background: Paracoccidioidomycosis is a systemic infection caused by the fungus Paracoccidioides. It may present in two forms: an acute/subacute form, whose most frequent manifestations include weight loss, fever, anemia, and adenopathy, and a chronic condition with mainly respiratory symptoms. Digestive symptoms, although they may occur, are not frequently reported. Paracoccidioidomycosis usually affects adult male agricultural workers; thus, its presentation in children is rare. Case report: We describe the case of a 9-year-old male patient diagnosed with paracoccidioidomycosis, who showed abdominal pain and diarrhea as initial manifestations of the disease. Conclusions: This case is reported not only because of the age of presentation but also due to the existence of digestive symptoms from the onset of the disease, both infrequently reported in the literature.

Resumen Introducción: La paracoccidioidomicosis es una infección sistémica producida por el hongo Paracoccidioides. Se puede presentar de dos formasuna forma aguda/subaguda, cuyas manifestaciones más frecuentes incluyen pérdida de peso, fiebre, anemia y adenopatías, y una forma crónica con manifestaciones principalmente respiratorias. Las manifestaciones digestivas, aunque pueden presentarse, no se reportan frecuentemente. La paracoccidioidomicosis afecta usualmente a varones adultos que trabajan en labores agrícolas, por lo que su presentación en niños es poco frecuente. Caso clínico: Se describe el caso de un paciente de sexo masculino de 9 años de edad con diagnóstico de paracoccidioidomicosis, con dolor abdominal y diarrea como manifestaciones iniciales de la enfermedad. Conclusiones: Se reporta este caso, no solamente por la edad de presentación, sino también por la existencia de síntomas digestivos desde el inicio de la enfermedad, ambos reportados en forma infrecuente en la literatura.

Síndrome destructivo de línea media secundario a infección por Paracoccidioides sp. Reporte de un caso

El síndrome destructivo de línea media es un grupo de enfermedades inflamatorias y tumorales destructivas del área centrofacial, entre las cuales la paracoccidioidomicosis es una de las etiologías a considerar en los países del trópico. La paracoccidioidomicosis es causada por hongos del género Paracoccidioides. Su forma de blastoconidia favorece la diseminación hematógena, afectando diversos tejidos como glándulas suprarrenales, tejido retículo-endotelial o mucosa oral, esta última donde puede manifestarse como un síndrome destructivo de línea media. Presentamos un caso de paracoccidioidomicosis con afección en cavidad oral, el cual debutó como un síndrome destructivo de línea media crónico, asociado a compromiso grave de la vía aérea que requirió manejo quirúrgico por riesgo de obstrucción y presentó mejoría con manejo antimicótico sistémico.

Summary Midline destructive disease is a group of severe and destructive inflammatory and tumor diseases of the midface area, among which paracoccidioidomycosis is one of the main etiologies in tropical countries. Paracoccidioidomycosis is an endemic mycosis caused by fungi of the genus Paracoccidioides. Its blastoconidia form favors hematogenous spread, affecting various tissues such as adrenal glands, reticulo-endothelial tissue, or oral mucosa, where it can manifest as a destructive midline syndrome. We present a case of paracoccidioidomycosis with affection in the oral cavity, which debuted as a chronic midline destructive disease with sever airway compromise that required surgical treatment for the risk of obstruction of the airway. The patient received systemic treatment with good response.

Afectación esofágica y pulmonar por paracoccidioidomicosis en paciente inmunocompetente: reporte de caso / Esophageal and Pulmonary Involvement Caused by Paracoccidioidomycosis in Immunocompromised Patient: Case Report

Resumen La paracoccidioidomicosis es una infección fúngica endémica de América del Sur, que afecta predominantemente a los hombres y, según su campo laboral, granjeros y agricultores. Es ocasionada por la aspiración del hongo en su forma micelar y debuta en tres formas de presentación: aguda, subaguda y crónica; esta última es más frecuente en adultos, cuyo tratamiento dependerá de los azoles, anfotericina B y sulfonamidas. El presente caso trata de un hombre de 57 años, colombiano, agricultor, sin antecedentes patológicos, quien presentaba dos meses de disfagia para sólidos que progresó a líquidos, sialorrea y pérdida de peso, a quien se le realizó endoscopia de vías digestivas altas y se observaron lesiones blanquecinas, por lo cual se realizó una biopsia que evidenció levaduras en múltiple gemación compatibles con paracoccidioidomicosis; a su vez, se observó en una tomografía de tórax compromiso parenquimatoso intersticial generalizado; posteriormente, recibió tratamiento con itraconazol, con el que mostró mejoría y resolución del cuadro clínico. En vista de que América del Sur es endémica de la patología descrita y puede presentarse de forma diseminada en inmunocompetentes, se debe tener en cuenta en aquellos pacientes que poseen factores de riesgo, sintomatología y hallazgos en estudios de extensión sugestivos de dicha enfermedad, dado el gran espectro de presentación de la infección, para así dar tratamiento oportuno y dirigido.

Abstract Paracoccidioidomycosis (PCM) is a fungal infection endemic to South America. It predominantly affects men, depending on their work field: farmers and agriculturists. Paracoccidioidomycosis is caused by the aspiration of the fungus in its micellar form and manifests in three conditions: acute, subacute, and chronic; the latter is more frequent in adults, whose treatment will depend on azoles, amphotericin B, and sulfonamides. This case concerns a 57-year-old Colombian man, a farmer with no pathological history who showed dysphagia for solids that progressed to liquids, sialorrhea, and weight loss for two months. He underwent upper GI endoscopy, and whitish lesions were observed; thus, he was biopsied, displaying yeasts in multiple gemmations compatible with paracoccidioidomycosis. In turn, a chest CT scan showed generalized interstitial parenchymal involvement. Subsequently, he was treated with itraconazole, showing improvement and resolution in his clinical picture. Since the pathology described is endemic in South America and can be disseminated in immunocompromised patients. Given the broad infection spectrum, consideration should be given to patients with risk factors, symptomatology, and findings in extension studies suggesting this disease to provide timely and specific treatment.

Paracoccidioidomicose afetando a mucosa bucal: relato de caso / Paracoccidioidomycosis affecting the buccal mucosa: case report / Paracoccidioidomicosis con afectación de la mucosa oral: relato de caso

Introdução: A paracoccidioidomicose é uma infecção micótica sistêmica com manifestações pulmonares primária que podem apresentar lesões cutâneas e orais. É mais comum no Brasil e em alguns outros países da América Latina, representando um importante problema de saúde pública devido às suas características potencialmente fatais. Relato de caso: Trabalhador rural de 53 anos, fumante e etilista, apresentando lesão ulcerada de aspecto moriforme em mucosa bucal direita. Realizou-se biópsia incisional cujo laudo histopatológico foi de paracoccidioidomicose. O paciente foi encaminhado ao médico infectologista para tratamento por meio de itraconazol (200mg por dia) por 18 meses. Após 03 meses de tratamento já apresentava regressão da lesão. Considerações Finais: Portanto, o objetivo deste trabalho é enfatizar a importância do cirurgião-dentista no reconhecimento das lesões oral e realização da biópsia para o correto diagnóstico e manejo desta doença por meio de um relato de caso clínico... (AU)

Paracoccidioidomycosis is a systemic mycotic infection with primary pulmonary manifestations that can present cutaneous and oral lesions. It is more common in Brazil and some other Latin American countries, representing an important public health problem due to its potentially fatal characteristics. Case report: 53-year-old rural worker, smoker and drinker, presenting an ulcerated lesion with a moriform aspect in the right oral mucosa. An incisional biopsy was performed, and the histopathological report was of paracoccidioidomycosis. The patient was referred to the infectious disease physician for treatment with itraconazole (200mg per day) for 18 months. After 03 months of treatment, he already had regression of the lesion. Final Considerations: Therefore, the objective of this paper is to emphasize the importance of the dentist in recognizing oral lesions and performing a biopsy for the correct diag... (AU)

La paracoccidioidomicosis es una infección micótica sistémica con manifestaciones pulmonares primarias que pueden presentar lesiones cutáneas y bucales. Es más común en Brasil y algunos otros países de América Latina, lo que representa un importante problema de salud pública debido a sus características potencialmente fatales. Caso clínico: trabajador rural de 53 años, fumador y bebedor, con lesión ulcerada de aspecto moriforme en mucosa oral derecha. Se realizó biopsia incisional y el informe histopatológico fue de paracoccidioidomicosis. El paciente fue remitido al médico de enfermedades infecciosas para tratamiento con itraconazol (200 mg al día) durante 18 meses. Después de 03 meses de tratamiento, ya tenía regresión de la lesión. Consideraciones finales: Por lo tanto, el objetivo de este trabajo es enfatizar la importancia del odontólogo en el reconocimiento de las lesiones bucales y la realización de una biopsia para el correcto diagnóstico y manejo de esta enfermedad a través de la presentación de un caso clínico... (AU)

Multiparametric assay of screening for the diagnosis of mycoses of interest in Public Health: standardization of methodology / Ensaio multiparamétrico de triagem para diagnóstico de micoses de interesse em Saúde Pública: padronização da metodologia

The standardization and validation of a multiplex assay requires the combination of important parameters such as sensitivity and specificity, acceptable levels of performance, robustness, and reproducibility. We standardized a multiparametric Dot-blot aimed at the serological screening of paracoccidioidomycosis, histoplasmosis, and aspergillosis. A total of 148 serum were evaluated: 10 from healthy subjects, 36 from patients with paracoccidioidomycosis, 62 from patients with histoplasmosis, and 40 from patients with aspergillosis. It was found that the multiparametric Dot-blot showed a high percentage of cross-reactivity. However, when evaluated individually, in the serological screening of histoplasmosis, a good performance was observed when compared to the double immunodiffusion assay, considered the gold standard test, with 100% co-positivity and 83.3% co-negativity. The performance of serological screening for aspergillosis was not satisfactory when compared to double immunodiffusion, showing 71.4% co-positivity and 100% co-negativity. The evaluation of the stability of nitrocellulose membranes showed that membranes sensitized with H. capsulatum antigen remained stable for 90 days and those sensitized with A. fumigatus antigen for 30 days. We conclude that the use of crude antigens was not suitable for the standardization of the multiparametric Dot-blot assay, due to the high cross-reactivity, and that further tests should be performed with purified proteins (AU).

A padronização e validação de um ensaio multiplex requer a combinação de parâmetros importantes, como sensibilidade e especificidade, níveis aceitáveis de desempenho, robustez e reprodutibilidade. Este trabalho padronizou um Dot-blot multiparamétrico visando a triagem sorológica da paracoccidioidomicose, histoplasmose e aspergilose. Foram avaliadas 148 amostras de soro: 10 de indivíduos saudáveis, 36 de pacientes com paracoccidioidomicose, 62 de pacientes com histoplasmose e 40 de pacientes com aspergilose. Verificou-se que o Dot-blot multiparamétrico apresentou elevado percentual de reatividade cruzada. Entretanto, quando avaliado individualmente, na triagem sorológica da histoplasmose observou-se bom desempenho quando comparado ao ensaio de imunodifusão dupla, considerado o teste padrão ouro, com 100% de co-positividade e 83,3% de co-negatividade. O desempenho da triagem sorológica da aspergilose não foi satisfatório quando comparado a imunodifusão dupla, apresentando 71,4% de co-positividade e 100% de co-negatividade. A avaliação da estabilidade das membranas de nitrocelulose mostrou que membranas sensibilizadas com antígeno de H. capsulatum permaneceram estáveis por 90 dias e as sensibilizadas com antígeno de A. fumigatus, por 30 dias. Concluímos que o uso de antígenos brutos não foi adequado para a padronização do ensaio de Dot-blot multiparamétrico, devido ao alto índice de reatividade cruzada, e que novos testes devem ser realizados com proteínas purificadas (AU).

Paracoccidioidomicosis diseminada en paciente inmunocompetente: reporte de caso / Disseminated Paracoccidioidomycosis in immunocompetent patient: case report

Resumen La Paracoccidioidomicosis (PCM) es una infección micótica endémica en Latinoamérica que se caracteriza por compromiso multiorgánico. El diagnóstico tardío y la diseminación sistémica favorecen complicaciones como falla respiratoria e insuficiencia suprarrenal que condicionan el desenlace del paciente. Se presenta el caso de un paciente de 51 años de edad, procedente de la costa pacífica colombiana, inmunocompetente con PCM diseminada a sistema nervioso central (SNC), pulmones y glándulas suprarrenales con debut clínico de síndrome neurológico. Durante estancia hospitalaria presenta pico febril, colapso hemodinámico, aci dosis metabólica severa e hiperlactatemia. Se hemocultivó e inició tratamiento antimicrobiano de amplio espectro con piperacilina-tazobactam (4.5 gr/IV cada 8 horas), vancomicina (15 mg/kg) más anfotericina B desoxicolato (1 mg/kg/dia) y se trasladó a unidad de cuidado intensivo. En la muestras de tejido suprarrenal se identificaron levaduras multigemantes de Paracoccidioides spp e inflamacion crónica granulomatosa. A los seis días posteriores a su ingreso, el paciente continuó con deterioro hemodinámico, desequilibrio electrolítico, shock séptico e insuficiencia suprarrenal que conllevó a su deceso a pesar de las medidas terapéuticas establecidas. Se intenta exponer el desafío que representa el diagnóstico de PCM sistémica y promover su sospecha clínica para poder identificar la enfermedad de forma oportuna y evitar complicaciones que conduzcan a un desenlace fulminante.

Abstract Paracoccidioidomycosis (PCM) is an endemic fungal infection in Latin America characterized by multi-organ involvement. Late diagnosis and systemic dissemina tion favor complications such as respiratory failure and adrenal insufficiency, which determine the outcome of the patient. We present the case of a 51-year-old patient from the Colombian Pacific coast, immunocompetent with PCM spread to the central nervous system (CNS), lungs, and adrenal glands with a clinical debut of the neurological syndrome. During a hospital stay, he presented fever peak, hemodynamic collapse, severe metabolic acidosis, and hyperlactatemia. Blood culture and began broad-spectrum antimicrobial treatment with piperacillin-tazobactam (4.5 gr / IV every 8 hours), vancomycin (15 mg/kg) plus amphotericin B deoxycholate (1 mg/kg/day) and was transferred to the intensive care unit. Paracoccidioides spp multigene yeasts and chronic granulomatous inflammation were identified in adrenal tissue samples. Six days after admission, the patient continued with hemodynamic deterioration, electrolyte imbalance, septic shock, and adrenal insufficiency that led to death despite the established therapeutic measures. The aim is to expose the challenge posed by the diagnosis of systemic PCM and promote its clinical suspicion to identify the disease promptly and avoid complications that lead to a fulminant outcome.

Oral manifestations of systemic fungal infections: 25-year experience in an endemic region

Some mycoses are endemic. They develop through hematogenous spread, causing a generalized infection, usually with secondary mucosal involvement.The aim of this observational and retrospective study was to report the prevalence and characteristics of oral lesions in patients diagnosed with systemic fungal infections (SFI) over a 25-year period in southern Brazil. Demographic (age, sex, ethnicity, occupation) and clinical (anatomical location, symptoms,histopathological diagnosis and management) data from the medical records of patients with SFI were collected from 1995 to 2019. 34 cases of SFI were found, of which 31 (91.18%) were diagnosed as paracoccidioidomycosis (PCM) and 3 (8.82%) as histoplasmosis. Men were much more affected (n = 31; 91.18%), with an average age of 46.9 years. Most patients (n = 18; 58.06%) were Caucasian; 48% (n = 15) were farm/rural workers and the most affected region was the jugal mucosa (n = 13; 25.49%) followed by the alveolar ridge (n = 12; 23.52%). All patients with histoplasmosis were immunocompetent men (mean age: 52.67 years), and the palate was the most affected. All patients underwent incisional biopsy and were referred to an infectologist. The dentist has an essential role in the recognition of SFI, whose oral manifestations may be the first sign. SFI should be included in differential diagnosis in patients from endemic areas. In addition, the inevitable human mobility and globalization make knowledge of these mycosesnecessary worldwide, especially since advanced cases in immunocompromised patients can be fatal.