Disseminated paracoccidioidomycosis in a liver transplant patient

Abstract Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.

Serological diagnosis of paracoccidioidomycosis using a Paracoccidioides spp. comercial antigen and the counterimmunoelectrophoresis method

ABSTRACT Purpose: In-house Paracoccidioides spp. antigens are commonly used in the serological diagnosis of paracoccidioidomycosis (PCM). The sensitivity and specificity of a commercial Paracoccidioides spp. antigen was assessed for PCM serological testing. Method: Counterimmunoelectrophoresis and double immunodiffusion were used to evaluate the Paracoccidioides ID Antigen reagent in sera from PCM cases and patients with other diseases. Results: All active PCM sera (n=24) were reactive using counterimmunoelectrophoresis (sensitivity = 100%), including 11 cases of infection by P. brasiliensis sensu stricto and one by P. americana. Fifteen (88%) out of 17 sera from patients on treatment or cured were reactive, including one case of P. lutzii infection. One to three bands of antigen-antibody precipitate were observed on the agarose gel, with a predominance of two to three bands in the test with untreated PCM sera or at the beginning of antifungal therapy. All sera from patients with histoplasmosis (n=7), aspergillosis (n=5), and other diseases (n=27) tested negative (specificity = 100%). The overall sensitivity and specificity using the commercial antigen and double diffusion test were 75% and 100%, respectively. Conclusion: The commercial antigen performed satisfactorily and may contribute to the dissemination of the use of serological tests for the PCM diagnosis.

Intestinal Paracoccidioidomycosis: Case report and systematic review

ABSTRACT Background: Paracoccidioidomycosis is a systemic mycosis considered endemic and limited to Latin America with the majority of registered cases originating from Brazil. The purpose of this paper was to report a case of a female patient with paracoccidioidomycosis mimicking inflammatory bowel disease and to systematically review available cases of the intestinal presentation of this infectious disease. Case report: Female patient, 32-years old, previously asymptomatic, presenting with acute pain in the lower right abdomen, associated with signs of peritoneal irritation and abdominal distension. Urgent surgery was performed, which identified a severe suppurative perforated ileitis. The anatomopathological study revealed fungal structures shaped as a ship's pilot wheel in Grocott-Gomori's staining, suggestive of Paracoccidioides spp. Methods: Studies were retrieved based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), Embase, and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. Simple descriptive analysis was used to summarize the results. Results: Our search strategy retrieved 581 references. In the final analysis, 34 references were included, with a total of 46 case reports. The most common clinical finding was abdominal pain and weight loss present in 31 (67.3%) patients. Most patients were treated with itraconazole (41.3%) and amphotericin B (36.9%). All-cause mortality was 12.8%. Conclusions: Paracoccidioidomycosis should be suspected in endemics areas, specially as a differential diagnosis for inflammatory bowel disease. Endoscopic tests and biopsy are useful for diagnosis and treatment with antifungal drugs seem to be the first treatment option to achieve a significant success rate.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Paracoccidioidomycosis: an uncommon clinical presentation

Abstract Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400 mg/day in the first month, decreased to 200 mg/day until the sixth month of treatment.

Leishmaniasis mucocutánea con manifestacion oral: reporte de un caso / Mucocutaneous leishmaniasis with oral manifestation: case report

La Leishmaniasis es un grupo de enfermedades transmitidas por vectores y causada por la Leishmania, un parásito intracelular, que se presenta de preferencia en regiones tropicales y subtropicales. Se manifiesta mediante un amplio rango de formas clínicas como la cutánea, mucocutánea, y visceral, dependiendo de la especie y respuesta inmunológica del paciente. Se presenta el caso de un hombre de 35 años que acudió derivado a Unidad de Estomatología del Hospital Señor del Milagro, Salta, Argentina, presentando en la cavidad oral lesión, granulomatosa, ulcerada, dolorosa a la palpación, única, en paladar blando, de tres meses de evolución. Se realizaron estudios serológicos, parasitológicos y PCR. Los ELISAs lisados, PCRs y cultivos de materiales de lesiones fueron positivos, confirmando diagnóstico de leishmaniasis mucocutánea. El paciente fue derivado al Servicio de Dermatología donde recibió tratamiento con Antimoniato de Meglumina, con repuesta clínica favorable. El conocimiento de las manifestaciones orales puede llevar al diagnóstico clínico de leishmaniasis mucocutánea por parte del odontólogo, pudiendo entregar un tratamiento oportuno y a la vez ayudar al paciente, evitando complicaciones de esta enfermedad.

Leishmaniasis is a group of vector-borne diseases caused by Leishmania, an intracellular parasite, which occurs preferentially in tropical and subtropical regions. It manifests itself through a wide range of clinical forms such as cutaneous, mucocutaneous, and visceral, depending on the species and the patient's immune response. We present a case of a 35-year-old man who was referred to the Stomatology Unit of the Señor del Milagro Hospital, Salta, Argentina, presenting in the oral cavity lesion, granulomatous, ulcerated, painful on palpation, unique, soft palate with three months of evolution. Serological, parasitological and PCR studies were performed. Lysed ELISAs, PCRs and cultures of lesion materials were positive, confirming diagnosis of mucocutaneous leishmaniasis. The patient was referred to the Dermatology Service where he received treatment with Meglumine Antimony, with favorable clinical response. The knowledge of the oral manifestations can lead to the clinical diagnosis of mucocutaneous leishmaniasis by the dentist, being able to provide timely treatment and at the same time help the patient, avoiding complications of this disease.

Perfil sorológico dos pacientes com suspeita clínica de paracoccidiodomicose avaliados pelo Instituto Adolfo Lutz no ano de 2016 / Serological profile of patients with clinical suspicion of paracoccidiodomycosis evaluated by Instituto Adolfo Lutz in 2016

Oitenta porcento dos casos de paracoccidioidomicose (PMC) ocorrem no Brasil. As regiões brasileiras com maior número de casos são: sul, sudeste e centro-oeste, sendo emergente no norte e nordeste. A imunodifusão dupla em gel de agarose assume grande importância no diagnóstico, por permitir o monitoramento da doença e por oferecer subsídios para levantamentos soroepidemiológicos. O objetivo deste trabalho foi de avaliar e caracterizar os pacientes atendidos no Laboratório de Imunodiagnóstico das Micoses do Instituto Adolfo Lutz de São Paulo, em 2016. Trata-se de um estudo retrospectivo realizado utilizando-se dados secundários e avaliando-se as seguintes informações: idade, sexo, procedência do pedido médico, resultado e histórico sorológico dos pacientes. Dos 1.408 pacientes, 12,8% apresentaram reatividade sorológica para Paracoccidioides brasiliensis. Destes, 42,5% não possuiam histórico sorológico, sendo considerados como casos novos da doença. A classificação dos pacientes reagentes por gênero demonstrou que 83,4% eram do sexo masculino, com razão de masculinidade de 5:1. A faixa etária variou de um (1) a 92 anos, e aproximadamente 40% dos pacientes eram da faixa etária de 41 a 60 anos. Este estudo demonstra e reforça a importância da implementação dos estudos soroepidemiológicos como ferramenta auxiliar para nortear as ações de vigilância e políticas em saúde na PCM.

Eighty percent of paracoccidioidomycosis (PMC) cases occur in Brazil. The highest numbers occur in south, southeast and center-west region, being emergent in the north and northeast areas. The double immunodiffusion in agarose gel is valuable for its diagnosis, as it allows the monitoring of the disease and offers subsidies for the seroepidemiological surveys. This study evaluated and characterized the patients attended in 2016 at the Mycoses Immunodiagnosis Laboratory of Adolfo Lutz Institute of São Paulo. This retrospective study, based on the secondary data, evaluated the information: age, sex, medical request origin, result and serological history of the patients. Of 1,408 patients, 12.8% presented positive serological reactivity for Paracoccidioides brasiliensis. Of them, 42.5% had no serological history and they were considered as new cases. The classification of reactive patients by gender showed that 83.4% were males, being the masculinity ratio of 5:1. The age range was one (1) to 92 years old, and ±40% of the patients were of age ranging from 41-60 years old. This study reinforces the importance of the implementation of the seroepidemiological studies as to guide the surveillance actions and the public health politics in PCM.

Diagnóstico de la paracoccidioidomicosis / Diagnosis of paracoccidioidomycosis

La paracoccidioidomicosis es una micosis sistemática, endémica de amplias regiones de América Latina, causada por un hongo termodimorfo, Paracoccidioides brasiliensis. Afecta de manera predominante a individuos de mediana edad y sexo masculino, en particular aquellos que cumplen tareas rurales. la infección se adquiere por vía inhalatoria, y puede diseminarse por vía hemática a diversos órganos y tejidos. La enfermedad puede evolucionar en forma aguda, subaguda o crónica. El diagnóstico presuntivo de la paracoccidioidomicosis se sustenta en los antecedentes epidemiológicos del paciente y en las manifestaciones clínicas. El diagnóstico etiológico clásico consiste en la visualización, el aislamiento y la identificación del agente causal, o bien el empleo de pruebas serológicas para determinar la presencia de anticuerpos específicos en sangre. Se presentan tres casos de paracoccidioidomicosis en pacientes varones, dos con formas agudas de la enfermedad y el restante con una forma crónica. En todos los casos, el diagnóstico se efectuó por los hallazgos de la microscopia, los cultivos y las pruebas serológicas

Paracoccidioidomycosis is a systemic mycosis, endemic to large regions of Latin America, caused by a thermodimorphic fungus, Paracoccidioides brasiliensis. It predominantly affects middle-aged and male individuals, particularly those who perform rural tasks. The infection is acquired by inhalation, and it can spread by blod to various organs and tissues. The disease can evolve in acute, subacute or chronic form. The presumptive diagnosis of paracoccidiodomycosis is based on the patient's epidemiological history and clinical manifestations. The classic etiological diagnosis consists of visualization, isolation and identification of the causative agent, or the use of serological tests to determine the presence of specific antibodies in the blood. There are threee cases of paracoccidioidomycosis in male patients, two with acute forms of the disease and the remaining with a chronic form. In all cases, the diagnosis was made by the findings of microscopy, cultures and serological tests

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.

Características clínicas y epidemiológicas de pacientes con paracoccidioidomicosis diagnosticados en un hospital de Resistencia, Chaco / Clinical and epidemiological characteristics of patients with paracoccidioidomycosis diagnosed in a hospital of Resistencia, Chaco

Con el objetivo de describir las características clínico-epidemiológicas de la paracoccidioidomicosis, se realizó un estudio descriptivo de los casos diagnosticados por el Servicio de Microbiología Clínica del hospital de adultos Dr. Julio C. Perrando, de la ciudad de Resistencia (Chaco, Argentina). Entre 2011 y 2014 se detectaron 46 casos. En 2013 y 2014 se constató un incremento de la tasa de incidencia de alrededor de 4 veces con respecto a los anos anteriores. La forma crónica fue la predominante, con una media de edad de los pacientes de 53 anos. Del total de ellos, a 39 se les realizaron pruebas serológicas. En 15 de 39 casos, las pruebas serológicas fueron la única herramienta diagnóstica, mientras que en 4 de estos casos con diagnóstico microbiológico, la prueba resultó no reactiva. La inclusión de la paracoccidioidomicosis en el diagnóstico diferencial de pacientes de áreas endémicas que presentan un síndrome infeccioso inespecífico y la aplicación de las herramientas diagnósticas disponibles contribuyen al diagnóstico oportuno, así como a disminuir las secuelas de esta afección y su impacto socioeconómico.

In order to describe the clinical and epidemiological characteristics of paracoccidioidomycosis, a descriptive study of all the cases diagnosed by the Clinical Microbiology Service at Dr. Julio C. Perrando hospital in the city of Resistencia (Chaco Province, Argentina) was conducted. Between 2011 and 2014, 46 cases were detected. In the period 2013-2014, an almost 4-fold increase in the incidence rate was detected. The chronic form of the disease was predominant with an average age of 53 years. Serological tests in 39 out of 46 patients were performed. In 15 of 39 patients, serological tests were the only diagnostic tool while in 4 patients with a microbiological diagnosis serological tests were non-reactive. In patients from endemic areas with non-specific infectious syndrome it is important to include paracoccidioidomycosis in the differential diagnosis and to apply all available diagnostic tools to reach a timely diagnosis and to reduce the long-term sequelae and their socio-economic impact.

Neuroparacoccidioidomicosis: para tener presente / Neuroparacoccidiodomycosis to keep in mind:

La paracoccidioidomicosis (PCM) es una micosis endémica de zonas tropicales y subtropicales, con mayor prevalencia en América Latina, producida por especies del género Para-coccidioides. Es una micosis profunda sistémica que en su forma crónica afecta principalmente a varones adultos. La afectación del sistema nervioso central (SNC) está descrita en un 10-27%. Nosotros presentamos dos casos con mani-festación neurológica al ingreso

Paracoccidioidomycosis (PCM) is an endemic mycosis, from tropical and subtropical zones, with a higher prevalence in Latin America, produced by species of the genus Paracoccidioides. It is a deep chronic systemic my-cosis, which mainly affects adult males. The involvement of the central nervous system (CNS) is described in 10-27%. We present two cases with neurological manifestation upon admission.

Paracoccidioidomycosis manifested by sarcoidosis-like cutaneous lesions and caused by Paracoccidioides brasiliensis sensu stricto (S1a)

Abstract: Molecular studies have shown more than one species of the genus Paracoccidioides to be the causal agent of paracoccidioidomycosis. Efforts have been made to correlate the identified species with epidemiological and clinical data of patients, aiming to determine the real meaning and impact of new species. Bearing this objective in mind, the authors report a clinical case of paracoccidioidomycosis, from São Paulo state, Brazil, that manifested as uncommon sarcoid-like cutaneous lesions and was caused by Paracoccidioides brasiliensis sensu stricto (S1a). The patient was treated with itraconazole 200mg/day for 12 months, with complete clinical remission.

Caso de autopsia: Paracoccidioides diseminada en paciente inmunocomprometido / Autopsy Case: Disseminated paracoccidiodes in an immunocompromised patient

Paracoccidioides brasiliensis is the predominant dimorphic fungal disease in Latin America. Males between 29 to 40 years of age are most often affected. Inhalation of the infecting particle produces a localized alveolitis. The organisms then may disseminate to the skin, mucous membranes, lymph nodes, adrenal glands, liver, spleen, bones, central nervous system and digestive tract, giving a multisystemic affectation, mainly in immunocompromised hosts. A male 34 years old with a history of immunocompromised VIH +, was studied. The characteristics in authopsy are described, with previous diagnosis of diseminated. Paracoccidioides brasiliensis, with intraalveolar hemorrhage, pleuritis and pericarditis. Deep systemic micosis and opportunistic are pathologies that present with increased frequency in recent years, mainly by the rise of the VIH+ infected population. Despite this circumstance, the coexistence of Paracoccidioide infection and VIH+ is scarce in the literature, and for that reason, we present this case of autopsy.

Diagnóstico oportuno de paracoccidioidomicosis diseminada en un adulto inmunocompetente / Timely diagnosis of disseminated paracoccidioidomycosis in an immunocompetent adult

La paracoccidioidomicosis es endémica en bosques húmedos subtropicales de América Latina. En sus formas agudas/subagudas se disemina agresivamente por el sistema linfoganglionar, pero en sus formas crónicas (más frecuentes) se presenta como diagnóstico diferencial de otras enfermedades que comprometen pulmón, orofaringe, piel y eventualmente cerebro. Presentamos el caso de un hombre con diagnóstico presuntivo de cáncer de pulmón con metástasis cerebrales. El hallazgo de levaduras multibrotadas y el posterior desarrollo de un hongo dimorfo identificado como Paracoccidioides sp. a partir de la biopsia de cerebro resultó en un cambio cardinal en el pronóstico y la terapéutica. Este caso resalta la importancia de considerar las micosis sistémicas en el diagnóstico diferencial de cuadros clínicos compatibles en personas que hayan habitado o transitado áreas endémicas.

Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America. Acute/subacute presentations involve an aggressive dissemination throughout the lymphatic system, while chronic forms (more frequent) arise as differential diagnosis for other conditions involving lung, oropharynx, skin, and eventually the brain. We present the case of a man referred for evaluation and treatment of a possible lung tumor with brain metastasis. The finding of multibudded yeasts and the microbiological isolation of a dimorphic fungus identified as Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis and treatment. This case alerts on the importance of considering systemic fungal diseases as differential diagnosis of compatible clinical presentations in patients who had lived in, or visited, endemic areas.

Paracoccidioidomicosis: crónica de una enfermedad olvidada / Paracoccidioidomycosis: chronicle of a neglected disease

La paracoccidioidomicosis (PCM) es una de las micosis sistémicas que son endémicas exclusivamente en América Latina. Está causada por hongos termodimorfos del género Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. Paracoccidioides habita y produce conidios infecciosos en suelos de zonas subtropicales húmedas. En Argentina está presente al norte del paralelo 34.5° S. Poco se sabe sobre su nicho ecológico específico, lo que dificulta el diseño de medidas de control de la PCM. La infección ocurre en hospederos susceptibles cuando inhalan conidios aerosolizados. Los trabajadores rurales varones son el grupo más expuesto a contraer PCM. La primoinfección puede ser asintomática o causar un cuadro respiratorio leve; este, a su vez, puede autolimitarse o progresar a enfermedad, ya sea pulmonar o diseminada. Existen dos formas de presentación: (i) aguda/subaguda, en niños, adolescentes y personas con sistemas inmunes comprometidos; y (ii) crónica progresiva, en adultos. La cicatrización de las lesiones resulta en secuelas fibróticas que pueden causar disfagia, disfonía, insuficiencia suprarrenal y obstrucción intestinal. Aunque existen herramientas para su diagnóstico, la PCM es rara vez sospechada precozmente porque sus manifestaciones clínicas iniciales son inespecíficas. Sumados, el diagnóstico tardío y la baja adherencia a los efectivos pero largos tratamientos antimicóticos permiten el avance de la enfermedad y el desarrollo de fibrosis tisular extensa, lo que compromete gravemente la función respiratoria y suprarrenal, altera permanentemente la calidad de vida del paciente y puede causar su muerte.

Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease is produced by thermodimorphic fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of members of this genus is the soil, where they produce infectious conidia. Little is known, however, about their specific ecologic niche(s), and this knowledge gap hampers the design of measures to control the infection. Rural male workers are the group most at risk of developing PCM. Infection occurs by inhalation of aerosolized conidia and may either be asymptomatic or cause mild respiratory symptoms. In turn, this primary infection may be self-limited or progress to severe pulmonary or disseminated disease. The disease has two clinical presentations: (i) acute or subacute (juvenile), frequent in children, adolescents and people with immunodeficiencies; and (ii) chronic progressive, in adults. Active lesions often resolve into fibrotic scars which can cause dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although efficient tools are available for diagnosis and treatment, the nonspecific nature of PCM clinical manifestations frequently delay the diagnosis. In addition, the poor adherence to long antifungal treatments allows the advance of the disease and the development of extensive fibrosis compromising severely and permanently respiratory and adrenal functions, thus altering the patient´s quality of life and even causing his/her death.

Leishmaniasis mucocutánea asociada a infección diseminada por paracoccidioides brasiliensis / MUCOCUTANEOUS LEISHMANIASIS ASSOCIATED TO DISEMINATED INFECTION BY PARACOCCIDIOIDES BRASILIENSIS

Leishmaniasis, a parasitic disease produced by a protozoan of the genus Leishmania, is triggered by the bite of an infected sandfly. It is endemic in tropical and subtropical areas of the Americas, places of poor socioeconomic health conditions and malnutrition. These conditions favor the entry of other pathogens such as the dimorphic fungus Paracoccidioides brasiliensis, responsible for Paracoccidioidomycosis (PCM), deep mycosis of inhalatory entry that initially affects the lungs; then skin, mucous membranes, lymph nodes and adrenal glands. The association of reported cases of Leishmaniasis and Paracoccidiodoimicosis in the same patient is infrequent. We point out the importance of the multidisciplinary approach for the correct diagnosis and treatment.

Pulmonary paracoccidioidomycosis: a case report of reactivation in a patient receiving biological therapy

Abstract Paracoccidioidomycosis is an endemic disease in Latin America that is rarely associated with immunosuppression and biological therapy. Herein, we report for the first time a case of pulmonary paracoccidioidomycosis reactivation after infliximab treatment. A 47-year-old man from Brazil received infliximab to treat psoriatic spondyloarthropathy and presented with cough, dyspnea, weight loss, and fever. Chest computed tomography revealed a pulmonary nodule and biopsy confirmed paracoccidioidomycosis. Treatment with sulfamethoxazole and trimethoprim was initiated for fungal infection and infliximab was reintroduced two months later. Considering his clinical improvement and favorable radiologic evolution, antifungal therapy was discontinued after 29 months.

Fatal septic shock caused by Paracoccidioides brasiliensis phylogenetic species S1 in a young immunocompetent patient: a case report

Abstract The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process. Together with P. lutzii, P. brasiliensis appears to be involved in severe cases of PCM.