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.

Paracoccidioidomycosis in a child: exuberant presentation due to the inadvertent use of systemic corticosteroids

Abstract: Paracoccidioidomycosis is a fungal infection that occurs in immunocompetent patients and are classified into two forms: the acute-subacute form, predominantly in young patients, and the chronic adult form that may present classic ulcerated lesions to rare sarcoid ones. We present the case of a boy whose infection began with sarcoid lesions but, after being mistakenly diagnosed with cutaneous sarcoidosis and treated (for three years) with prednisone, developed painful ulcerations throughout the body. After the correct diagnosis, with evidence of the fungus in histopathological and mycological examinations, the patient was properly treated with itraconazole for eight months and evolved with total remission of the disease.

Paracoccidioidomicose com repercussão oral: relato de caso em zona urbana / Paracoccidioidomycosis with oral impact: case report in an urban area

Objetivo: relatar um caso de paracoccidioidomicose (Pbmicose), diagnosticado pelo cirurgião-dentista, e o tratamento instituído a um morador de zona urbana. Relato de caso: paciente do sexo masculino, com 59 anos de idade, leucoderma, compareceu à clínica odontológica com lesão em boca há cerca de vinte dias e queixa de mobilidade dental na região anteroinferior. Durante a anamnese, constatou-se dificuldade respiratória, hipertensão controlada, tabagismo e etilismo crônico. No exame físico, foi observado aumento de volume do lábio inferior, linfadenopatia bilateral submandibular e lesões ulceradas com aspecto moriforme em mucosa bucal e gengiva inserida do elemento 31 ao 45. Foi realizada biópsia incisional na lesão com resultado positivo para Pbmicose. O paciente foi medicado com itraconazol e apresenta-se periodicamente para acompanhamento. Considerações finais: as lesões bucais dessa doença correspondem a úlceras crônicas e granulomatosas, semelhantes à lesão provocada pelo carcinoma epidermoide oral, assim, o cirurgião-dentista deve conhecer esta micose e considerá-la na elaboração do diagnóstico diferencial. (AU)

Objective: to report a case of paracoccidioidomycosis (Pbmycosis) diagnosed by the dentist, as well as the treatment applied to a resident of an urban area. Case report: male patient, 59 years old, white, referred to the dental clinic with a lesion in the mouth of around 20 days and complaint of tooth mobility in the anteroinferior region. The anamnesis showed respiratory distress, controlled hypertension, and chronic smoking and alcoholism. The physical examination showed increased volume of the lower lip, bilateral submandibular lymphadenopathy, moriform ulcerated lesions in the buccal mucosa, and gum insertion from tooth 31 to 45. An incisional biopsy was performed on the lesion with a positive result for Pbmycosis. The patient was treated with itraconazole and he shows up periodically for follow-up. Final considerations: the oral lesions of this disease correspond to chronic and granulomatous ulcers, similar to the lesion caused by the oral squamous cell carcinoma, thus, the dentist should understand this mycosis and consider it when producing the differential diagnosis. (AU)

Paracoccidioidomycosis with sarcoid-like lesions: a diagnostic challenge

Abstract Clinical presentation of paracoccidioidomycosis (PCM) can be diverse. Morphology and quantity of skin lesions depends on interactions between host immunity and fungus virulence. Diagnosis can be a challenge considering that this fungus has low virulence and some individuals have immunity to microorganism, which results in well-marked granulomas without visible microorganisms. We report herein a clinical presentation of sarcoid-like PCM, initially diagnosed as tuberculoid leprosy. This rare type of PCM is often mistaken for other types of chronic granulomatous diseases. Diagnosis was confirmed after 4 years when a special stain analysis helped in the identification of the specific etiologic agent.

Paracoccidioidomicosis colónica en un hospital de Lima - Perú: reporte de 4 casos / Colon Paracoccidioidomycosis in a hospital from Lima - Peru: report of 4 cases

La paracoccidioidomicosis es la micosis más prevalente de Sudamérica. En nuestro medio la afectación mucocutánea y linfática suele ser la de mayor prevalencia, siendo el compromiso intestinal pocas veces reportado. Se reportan 4 casos de afectación colónica con manifestación de dolor abdominal, diarrea crónica y disminución de peso en los cuales el diagnóstico se realizó a través de la anatomía patológica con la tinción de Gomori. La edad promedio fue de 29 años. La colonoscopía reveló presencia de múltiples úlceras en colon y en íleon distal. Como comorbilidad se encontró VIH en un paciente

Paracoccidioidomycosis is the most prevalent mycosis in South America. Mucocutaneous and lymph node involvement is the most frequent affectation of this disease in our country, with the intestinal commitment rarely reported. We report 4 cases of colonic manifestation with abdominal pain, chronic diarrhea, and weight loss. The diagnosis was made with biopsy and Gomori stain. The average age was 29 years old. The colonoscopy showed many ulcers in the ileum distal and colon. We found VIH as comorbidity in one patient

Sarcoid-like cutaneous lesions in chronic adult paracoccidioidomycosis: report of two cases

ABSTRACT This study reports two cases of chronic paracoccidioidomycosis with sarcoid-like cutaneous lesions. The patients began the treatment in 2013 at Hospital Universitário Clementino Fraga Filho (HUCFF) of the Universidade Federal do Rio de Janeiro (UFRJ). The first case (mild form) was treated with trimethoprim-sulfamethoxazole (8 mg /kg per day, orally) for three months and, then, with half the dose for nine months; the second (moderate form), with itraconazole (200 mg per day, orally) for 12 months. We point out the rareness of the sarcoid-like cutaneous lesions and the differential diagnoses for other granulomatous diseases.

Paracoccidioidomycosis in the spine: case report and review of the literature / Paracoccidioidomicose na coluna vertebral: relato de caso e revisão da literatura

ABSTRACT: CONTEXT: Paracoccidioidomycosis is a systemic form of mycosis that spreads hematogenously, secondarily to reactivation of lung infection or infection at another site or to new exposure to the causative agent. Few cases of bone involvement have been reported in the literature and involvement of the spine is extremely rare. CASE REPORT: We describe a case of a 68-year-old male patient with spondylodiscitis at the levels L4-L5 caused by presence of the fungus Paracoccidioides brasiliensis, which was diagnosed through percutaneous biopsy. The patient was treated with sulfamethoxazole and trimethoprim for 36 months, with complete resolution of the symptoms. CONCLUSION: Spondylodiscitis caused by the fungus Paracoccidioides brasiliensis is uncommon. However, in patients with chronic low-back pain who live or used to live in endemic regions, this infection should be considered as a possible differential diagnosis.

RESUMO: CONTEXTO: Paracoccidioidomicose é uma micose sistêmica de disseminação hematogênica, secundária a reativação de uma infecção pulmonar ou de outro sítio, ou a uma nova exposição ao agente causador. Poucos casos de envolvimento ósseo são relatados na literatura, e o acometimento da coluna vertebral é extremamente raro. RELATO DE CASO: Descrevemos o caso de um paciente masculino de 68 anos, apresentando espondilodiscite no nível L4-L5, causada pela presença do fungo Paracoccidioides brasiliensis, diagnosticada após biópsia percutânea. O paciente foi tratado com sulfametoxazol e trimetoprim por 36 semanas, com resolução completa dos sintomas. CONCLUSÃO: A espondilodiscite causada pelo fungo Paracoccidioides brasiliensis é incomum, mas, em pacientes portadores de lombalgia crônica que viveram ou vivem em regiões endêmicas, deve ser considerada como um possível diagnóstico diferencial.

Paracoccidioidomycosis and cryptococcosis with localized skin manifestations: report of two cases in the elderly

Abstract Distinct cases of Paracoccidioidomycosis and Cryptococcosis with atypical and localized skin manifestation on the upper limbs of two elderly patients are reported. In the 2nd one, he presented asymptomatic pulmonary cancer; the blood tests for fungal infection were negative, and the etiologic agents were seen in skin biopsy samples. This report emphasizes the importance of the differential diagnosis of infectious diseases in elderly patients.

Paracoccidioidomicosis: presentación inusual / Paracoccidioidomicosis: presentación inusual

Se presenta un paciente masculino, de 63 años de edad, con antecedentes de enfermedad de Leriche y colocación de prótesis vascular. Es internado en terapia intensiva por infarto intestinal e isquemia aguda de miembro inferior derecho por lo cual es intervenido quirúrgicamente. Mediante el hallazgo de Paracoccidioides sp en prótesis vascular y otros órganos internos, asociados a lesiones cutáneas y compromiso pulmonar, se realiza el diagnóstico de paracoccidioidomicosis crónica multifocal. Destacamos el compromiso de la prótesis como parte de la diseminación fúngica (AU)

A 63-year-old male patient with a history of Leriche disease and vascular prosthesis placement is reported. He is admitted to intensive care unit with intestinal infarct and acute ischemia of his right lower limb for which he underwent surgery. Paracoccidioides sp findings in vascular prostheses and other internal organs, associated with skin lesions and pulmonary involvement, allowed the diagnosis of chronic multifocal paracoccidioidomycosis. We emphasize the commitment of the prosthesis as part of fungal dissemination on this case (AU)

DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS / Efeito da dose resposta de Paracoccidioides brasiliensis no modelo experimental de artrite

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

A paracoccidioidomicose (PCM) é causada pelo fungo dimórfico Paracoccidioides brasiliensis (Pb) e corresponde à micose sistêmica de maior prevalência na América Latina. O objetivo do presente trabalho foi avaliar a dose resposta de leveduras do fungo para padronização do modelo experimental de artrite séptica. Os experimentos foram realizados com grupos de 14 ratos que receberam doses de 103, 104 ou 105 células de P. brasiliensis (Pb18). Os fungos foram injetados em 50 µL de solução salina em tampão fosfatado (PBS) diretamente na articulação do joelho dos animais. Os seguintes parâmetros foram analisados neste trabalho: a formação de edema nos joelhos infundidos com as células das leveduras e alterações radiológicas, anatopalógicas além de titulação de anticorpos por Elisa. Após 15 dias de infecção, os sinais de inflamação foram evidentes. Aos 45 dias, algumas características de dano e necrose foram observadas na cartilagem articular. A disseminação sistêmica do fungo foi observada em 11% dos animais inoculados, concluiu-se que o modelo experimental é capaz de mimetizar a PCM articular em humanos e que a dose de 105 leveduras representa a dose padrão para o desenvolvimento do modelo.

Paracoccidioidomicose (doença de Lutz-Splendore-Almeida): etiologia, epidemiologia e patogênese / Paracoccidioidomycosis disease (Lutz-Splendore-Almeida): etiology, epidemiology, and pathogenesis

A paracoccidioidomicose (PCM) é uma micose granulomatosa sistêmica, polimórfica, determinada pelos Paracoccidioides brasiliensis e P. lutzii e constitui-se em uma das 10 causas de morbimortalidade entre as doenças endêmicas parasitárias no Brasil. A atualização do conhecimento sobre sua etiologia, epidemiologia e patogênese constitui estímulo para que seja incluída no espectro do diagnóstico diferencial da prática médicarotineira, reconhecida com precocidade e tratada convenientemente, evitando-se que evolua com sequelas e morte.

Paracoccidioidomycosis (PCM) is a polymorphic systemic granulomatous mycosis determined by Paracoccidioides brasiliensis and P. lutzii and constitutes one of the 10 leading causes of morbidity and mortality by the parasitic diseases endemic in Brazil. The need for updates on the etiology, epidemiology, and pathogenesis is a for routinely including this disease in the differential diagnosis of current medical practice, recognizing it early and treating it properly, so as to avoid progression with sequelae and death.

Extra-pulmonary manifestations of paracoccidioidomycosis associated with acquired immunodeficiency syndrome: a case report

We present a patient with Paracoccidioidomycosis/HIV coinfection which has been investigated because of chronic monoarthritis and mucocutaneous lesions. A biopsy of the synovial membrane and skin revealed structures consistent with Paracoccidioides brasiliensis. At diagnosis, the count of CD4 + T cells was 44 cells/mm3. We emphasize the importance of clinical suspicion of Paracoccidioidomycosis in patients with HIV/AIDS who live in or are from risk areas.

Paracoccidioidomycosis in southern Rio Grande do Sul: a retrospective study of histopathologically diagnosed cases

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and is endemic to Brazil. The aim of this study was to perform a retrospective analysis of the PCM cases in the countryside south of Rio Grande do Sul, Brazil. The files from four histopathology laboratories located in the city of Pelotas were obtained, and all of the epidemiological and clinical data from the PCM diagnosed cases were collected for analysis. A total of 123 PCM cases diagnosed between 1966 and 2009 were selected. Of these patients, 104 (84.5%) were male, and 17 were female. The patients ranged from 02 to 92 years of age. Fifty-two cases (41.9%) were obtained from the oral pathology laboratory, and the remaining 71 cases (58.1%) were obtained from the three general pathology laboratories. Of all of the patients studied, 65.2% lived in rural zones and worked in agriculture or other related fields. Data on the evolution of this disease was available for 43 cases, and the time frame ranged from 20 to 2920 days (mean = 572.3 days). An accurate diagnosis performed in less than 30 days only occurred in 21% of the cases. PCM is endemic to the countryside of Rio Grande do Sul. Therefore, it is recommended that PCM be included as a differential diagnosis, mainly for individuals between 30 and 60 years of age, living in rural zones and who have respiratory signs and associated-oropharyngeal lesions.

Direcionamento de antígenos para células dendríticas in vivo: uma nova estratégia para o desenvolvimento de vacina na paracoccidioidomicose / Targeting antigens to dendritic cells in vivo: a new strategy for vaccine development in Paracoccidioidomycosis

A paracoccidioidomicose (PCM) é a micose sistêmica mais frequente no Brasil. Na última década, foi demonstrado que é possível enviar antígenos diretamente para as células dendríticas utilizando o anticorpo αDEC205 e na presença de um estímulo de maturação, o resultado é a indução de uma resposta imunológica. Verificamos que o anticorpo αDEC fusionado ao peptídeo P10 induziu uma resposta por células produtoras de IFN-γ após uma única dose em relação à administração de P10, mesmo tendo sido administrado em uma concentração menor. Entretanto, essa resposta não se manteve após segunda dose do anticorpo. Após desafio dos animais com P. brasiliensis, imunizados com duas doses do anticorpo quimérico, detectamos níveis de IFN-γ e IL-4 no tecido pulmonar estatisticamente maiores no grupo αDEC/P10 e ISO/P10 em relação à administração de P10, todos em presença de Poly I:C. Em ensaios de terapia, verificamos no pulmão de camundongos tratados com o anticorpo quimérico, principal órgão envolvido em modelo animal de PCM, baixa concentração de IFN-γ e IL-10 em relação aos controles. Em adição, ficou evidente que nos animais tratados com o anticorpo αDEC/P10 o tecido pulmonar está compatível com o tecido de animais não infectados, enquanto que na ausência de tratamento adequado encontramos aglomerados de leveduras e um tecido com aumento no infiltrado celular. Esses achados indicam uma boa evolução clínica em animais tratados e indicam que o direcionamento do P10 através do anticorpo quimérico αDEC/P10, na presença de Poly I:C, é uma estratégia promissora para terapia contra P. brasiliensis

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Brazil. In the last decade, it was demonstrated that antigens can be directly target to the dendritic cells using the antibody αDEC205 in the presence of a maturation stimulus, resulting in the induction of a strong immune response. We found that αDEC205 antibody fused to peptide P10 induced great response by IFN-γ producing cells after a single dose in relation to the administration of P10, although it has been administered in a lower concentration. However, this response was not maintained after second dose of antibody. Animals challenge with P. brasiliensis, after immunization with two doses of the chimeric antibody, produced high levels IFN-γ and IL-4 in lung tissue significantly higher in αDEC/P10 group in relation to the administration of P10, all in the presence of Poly I:C. In therapy assays, we found in the lungs of mice treated with the chimeric antibody, the main organ involved in an animal model of PCM, low concentration of IFN-γ and IL-10 compared to controls. In addition, it became evident that animals treated with αDEC/P10 antibody have a lung tissue much closer to that of non-infected tissue, while in the absence of suitable treatment we find clusters of yeasts and tissue filled with cellular infiltrates. Altogether, these findings show a clinical improvement in treated animals and indicate that targeting of P10 through the chimeric antibody αDEC/P10 in the presence of Poly I:C, is a promising strategy for therapy against P. brasiliensis

Sarcoid-like paracoccidioidomycosis presenting with perineural granuloma / Paracoccidioidomicose sarcoidica com granuloma perineural

Paracoccidioidomycosis presenting as a sarcoid-like plaque may be misdiagnosed as leprosy, especially when shared endemic areas are concerned. We report the case of a Brazilian male patient presenting with an ulcerated plaque on his left ear and neighboring areas. The plaque simulated tuberculoid leprosy type 1 reaction, both clinically and histopathologically. A perineural granuloma with no organisms detected by routine and Fite-Faraco staining reinforced that diagnosis. Paracoccidioidomycosis was confirmed only after a second biopsy, taken from the ulcerated area.

Paracoccidioidomicose expressando-se como placa sarcoídica pode ser confundida com hanseníase, especialmente em zonas endêmicas comuns às duas condições. Apresentamos um paciente brasileiro, com placa ulcerada na orelha direita e em áreas vizinhas que simulava, clinica e histopatologicamente, hanseníase tuberculoide em reação tipo 1. O encontro de granuloma perineural, sem parasitas detectáveis às colorações de rotina e Fite-Faraco, reforçou a hipótese de hanseníase. Apenas com uma nova biópsia, desta vez da área ulcerada, a paracoccidioidomicose pôde ser confirmada.

Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating / Paracoccidioidomicose: atualizacao epidemiologica, clinica, diagnostica e terapeutica

Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression, paracoccidioidomycosis is an important disease for dermatologists, who must be up-to-date about it. This article focuses on recent epidemiological data and discusses the new insights coming from molecular studies, as well as those related to clinical, diagnostic and therapeutic aspects. In the latter section, we give particular attention to the guideline on paracoccidioidomycosis organized by specialists in this subject.

Paracoccidioidomicose é micose sistêmica de evolução aguda a crônica e causada por espécies do gênero Paracoccidioides. Pela frequente expressão clinica tegumentar da paracoccidioidomicose os dermatologistas têm que se manter atualizados em relação à enfermidade. O presente trabalho tem enfoque na atualização epidemiológica, discutindo os avanços na área propiciados pela micológica molecular, nos aspectos clínicos incluindo avanços diagnósticos e se completa com a discussão terapêutica e nesse item com foco nos dados do consenso em paracoccidioidomicose elaborado por especialistas no tema.

The lung in paracoccidioidomycosis: new insights into old problems

OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial ...

Paracoccidioidomycosis: sarcoid-like form in childhood / Paracoccidioidomicose: forma clínica sarcoídica na infância

Paracoccidioidomycosis is a chronic, subacute or rarely acute mycosis, with visceral and cutaneous involvement. It is potentially fatal. Children account for about 5-10% of cases. In this study, we describe the relevance of discussing possible differential diagnoses as well as the importance of early treatment.

Paracoccidioidomicose é uma micose crônica, subaguda ou raramente aguda, com comprometimento visceral e tegumentar, sendo potencialmente fatal. As crianças representam cerca de 5 a 10% dos casos. A seguir, descreve-se a necessidade da discussão dos diagnósticos diferenciais cabíveis bem como a importância do início precoce do tratamento.