Neurohistoplasmosis y leishmaniasis cutánea en paciente inmunocompetente / Neurohistoplasmosis and cutaneous leishmaniasis in an immunocompetent patient

La histoplasmosis y la leishmaniasis son enfermedades olvidadas, endémicas en Argentina, y generalmente se asocian a inmunocompromiso. Presentamos el caso de un varón de 16 años, inmunocompetente, con histoplasmosis del sistema nervioso central y leishmaniasis cutánea. Inicialmente, el paciente presentó una lesión en la pierna de un mes de evolución seguida de paraparesia leve, diagnosticada como un proceso de desmielinización mediante estudios de imágenes. El cuadro fue tratado con altas dosis de corticoides y en 72 horas evolucionó a paraparesia grave con lesiones nodulares en las vértebras cervicales, observadas en las imágenes de resonancia magnética nuclear. Se aisló Histoplasma capsulatum de líquido cefalorraquídeo, genotípicamente identificado como perteneciente a la especie filogenética LamB. El paciente recibió tratamiento intravenoso con anfotericina B deoxicolato durante 30 días y posteriormente fluconazol e itraconazol oral durante un año. A los tres meses de iniciado el tratamiento con antifúngicos se reactivó la lesión de la pierna y en el examen directo se observaron amastigotes de Leishmania. La leishmaniasis cutánea fue tratada con antimoniato de meglumina intramuscular. La respuesta clínica al tratamiento de ambas enfermedades fue favorable.

Histoplasmosis and leishmaniasis are neglected and endemic diseases in Argentina, and generally are found associated with immunosuppression. We report the case of an immunocompetent 16-years-old man with simultaneous occurrence of central nervous system histoplasmosis and cutaneous leishmaniasis. Upon admission, the patient showed a one-month old skin lesion in a leg and mild paraparesis. Imaging studies detected thickening and edema in the spinal cord and the cerebrospinal fluid analysis was within normal range. The case was diagnosed as a demyelinating disorder and treated with high-dose short-term steroids. Seventy-two hours later the patient showed severe paraparesis and nuclear magnetic resonance imaging revealed nodular lesions in the spinal cord. Histoplasma capsulatum belonging to the phylogenetic species LamB was isolated from cerebrospinal fluid samples. The patient received intravenous antifungal therapy with amphotericin B for 30 days, followed by oral fluconazole and itraconazole for one year. Three months after initiation of antifungal treatment, the cutaneous lesion recrudesced and Leishmania amastigotes were observed on microscopic examination. The cutaneous leishmaniasis was treated with intramuscular meglumine antimoniate. The patient´s outcome was favorable after treatment for both diseases.

Criptococosis diseminada en paciente HIV con CD4 mayor a 500 / Disseminated cryptococcosis among an HIV-Infected person with CD4 Higher than 500 cel/µ

La criptococosis es la micosis sistémica más frecuente entre los pacientes con HIV SIDA. Su prevalencia oscila entre el 5% y el 25%, de acuerdo con la región geográfica que se considere. La localización habitual de esta micosis en el paciente VIH es el sistema nervioso central (SNC). La diseminación sanguínea del agente causal ocurre ante defectos de la inmunidad mediada por células, asociándose con frecuencia a linfomas, leucemia, enfermedades del sistema retículo endotelial. A partir de la eclosión del HIV se redujo un aumento significativo del número de casos, transformándose esta última condición en la causa favorecedora más importante.

Cryptococcosis is the most frequent systemic mycosis among patients with HIV AIDS. Its prevalence ranges between 5% and 25%, according to the geographical region considered. The usual location of this mycosis in the HIV patient is the central nervous system (CNS). Blood dissemination of the causative agent occurs due to defects of cell-mediated immunity, frequently associated with lymphomas, leukemia, reticuloendothelial system diseases. From the emergence of HIV, there was a significant increase in the number of cases, with the latter condition becoming the most important favorable cause

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS / Infecções fúngicas disseminadas com acometimento das supra-renais: descrição de dois pacientes brasileiros HIV-negativos

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

A paracoccidioidomicose e a histoplasmose são infecções fúngicas sistêmicas endêmicas no Brasil. As formas clínicas disseminadas são incomuns em pacientes imunocompetentes. Nós descrevemos dois pacientes HIV-negativos com infecções fúngicas disseminadas, paracoccidioidomicose e histoplasmose, que foram diagnosticadas por biópsias de lesões de supra-renal. Ambos foram tratados por períodos prolongados com antifúngicos orais, evoluindo com boa resposta terapêutica.

Phaeohyphomycosis: a clinical-epidemiological and diagnostic study of eighteen cases in Rio Grande do Sul, Brazil

The goal of this study was to review 18 cases of phaeohyphomycosis in Rio Grande do Sul. The records of all of the patients with a diagnosis of phaeohyphomycosis between 1995-2010 were reviewed. Twelve of the 18 patients (66.6%) were male. The average age of the patients was 50 years old (range: 16-74 years). Eleven patients (61%) presented with subcutaneous lesions. Seven patients (38.8%) had received a solid organ transplant. In all of the cases, the presence of melanin in the fungal cells was determined by Fontana-Masson staining of tissue sections and documented. Among the 18 patients, a total of 11 different fungal species were isolated. The causative organisms included Exophiala jeanselmei, Alternaria, Curvularia, Cladophialophora and Colletotrichum gloeosporioides. To our knowledge, this review reports the first case of subcutaneous phaeohyphomycosis caused by C. gloeosporioides in a lung transplant patient. The number of reported cases of phaeohyphomycosis has increased in the last decade. In a number of cases, this increased incidence may be primarily attributed to iatrogenic immunodeficiency.

Posterior fossa midline cryptococcoma in a patient with idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) is a rare disorder which is often diagnosed as HIV-negative AIDS in the light of poor immunity and AIDS-defining illnesses. We present a case of a 50-year-old male who presented with a midline posterior fossa tumour with ICL diagnosed as cerebellar cryptococcoma.

Vertebro-cerebral cryptococcosis mimicking tuberculosis: A diagnostic dilemma in countries with high burden of tuberculosis.

We report a case of a 30-year-old immunocompetent man with disseminated cryptococcosis who was initially treated with antitubercular therapy due to clinical and radiological diagnosis of vertebro-cerebral tuberculosis. The diagnosis of Cryptococcus infection was made due to incidental isolation of this fungus from blood culture with negative cerebrospinal fluid culture results. Though disseminated cryptococcosis with central nervous system, skeletal, and skin involvement is an uncommon manifestation of Cryptococcus neoformans infection, a high clinical suspicion and early initiation of therapy is needed to recognise and treat such patients efficiently.

Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del sistema nervioso central: Tercera parte / Importance of images and etiological diagnosis in immunocompromised patients with central nervous system involvement: Third part

A twenty four year-old male patient with a history of morbid obesity and acute lymphocytic leukemia diagnosed in 2003, underwent an autologous bone marrow transplantation the same year. He had two relapses of leukemia on 2003 and 2007. On January 2009, he underwent a double cord bone marrow transplantation with myeloablative conditioning and craneospinal radiotherapy. The patient received prophylaxis with aciclovir, cotrimoxazole and fluconazole. The latter was changed afterwards to posaconazole. On day 16 post-transplantation, fever and menin-geal signs appeared. The cerebrospinal fluid exam revealed pleocytosis with polymorphonuclear predominance. Empirical therapy was started with meropenem. Due to neurological impairment, at day 33, a brain magnetic resonance imaging (MRI) was performed, showing multiple hypodense supra and infratentorial nodules with peripheral edema. Biopsy, universal PCR for fungi and a new cerebrospinal fluid analysis were performed and amphotericin B was added showing a favorable response. He was discharged with itraconazole, as the universal PCR of brain tissue revealed Penicillium spp. This is the third report presented in this journal that stresses the importance of early neuroimaging, especially MRI to certify the involvement of the central nervous system in immunocompromised patients.

Paciente de 24 años, sexo masculino, con antecedente de obesidad mórbida que debutó con una leucemia linfática aguda (LLA) en el año 2003. Se le efectuó trasplante (Tx) de precursores hematopoyéticos, autólogo, recayendo el mismo año. En el año 2007 presentó una segunda recaída por lo que se le sometió a Tx doble de cordón como rescate en enero de 2009, con acondicionamiento mieloablativo y radioterapia cráneo-espinal recibiendo profilaxis con aciclovir, cotrimoxazol y fluconazol, el que fuera cambiado posteriormente a posaconazol. El día 16 post trasplante presentó fiebre y signos meníngeos, con LCR que revelaba una pleocitosis de predominio polimorfonuclear. Se inició terapia empírica con meropenem. Debido al deterioro neurológico, en el día 33, se le efectuó una resonancia magnética cerebral (RM) donde se evidenciaron múltiples nódulos hipodensos supra e infratentoriales con edema periférico. Se le realizó biopsia cerebral, cultivos, reacción de polimerasa en cadena (RPC) para hongos, nuevo estudio de LCR completo y se agregó anfotericina B deoxicolato presentando una respuesta favorable. Finalizada la terapia con anfotericina B se dio de alta con itraconazol ya que la RPC de tejido cerebral reveló Penicillium sp. Este es el tercer caso presentado en esta revista en los que enfatizamos la importancia de las neuroimágenes, en especial la RM, realizadas en forma precoz para certificar el compromiso del SNC en pacientes inmunocomprometidos.

Paracoccidioidomicose com comprometimento do sistema nervoso central: revisão sistemática da literatura / Paracoccidioidomycosis compromising the central nervous system: a systematic review of the literature

Este trabalho é o primeiro a realizar uma revisão sistemática dos casos de neuroparacoccidioidomicose disponíveis na literatura. Foram encontrados 257 casos em 81 trabalhos pesquisados pelo MEDLINE e LILACS, com maior número de publicações após as décadas de 1970-1980. Aproximadamente, 93 por cento dos pacientes eram homens, principalmente lavradores, com idade média de 43 anos. O quadro caracterizou-se por sintomatologia motora ou de hipertensão intracraniana. A forma crônica pseudotumoral predominou. O período médio de evolução foi de 4,9 meses. As lesões foram principalmente supratentoriais (66,8 por cento), localizando-se nos lobos frontais e parietais. A biópsia determinou o diagnóstico em 57,2 por cento dos casos e utilizaram-se métodos de neuroimagem em 64,6 por cento deles. Houve grande associação com a forma pulmonar da doença (59,1 por cento). A mortalidade foi de 44,1 por cento e 50,1 por cento dos sobreviventes evoluíram com sequelas, principalmente motoras. Assim, deve-se considerar a neuroparacoccidioidomicose no diagnóstico diferencial dos processos expansivos e meningoencefalíticos do sistema nervoso central para se estabelecer tratamento precoce e evitar seqüelas incapacitantes.

This study is the first systematic review of cases of neuroparacoccidioidomycosis available in the literature. Through searches in the MEDLINE and LILACS databases, 257 cases were found in 81 published studies, mainly after the 1970s-1980s. Approximately 93 percent of the patients were men, especially farm laborers, with a mean age of 43 years. The characteristic symptoms were motor deficits or intracranial hypertension. The chronic pseudotumoral form predominated. The mean period of evolution was 4.9 months. The lesions were mainly supratentorial (66.8 percent), located in the frontal and parietal lobes. The diagnosis was determined by biopsy in 57.2 percent of the cases and neuroimaging methods were used in 64.6 percent of them. A large proportion of the cases were associated with the pulmonary form of the disease (59.1 percent). The mortality rate was 44.1 percent, and 50.1 percent of the survivors developed sequelae, especially motor impairment. Thus, neuroparacoccidioidomycosis should be considered in the differential diagnosis for expansive and meningoencephalitic processes in the central nervous system, in order to establish early treatment and to avoid disabling sequelae.

Cryptococcal granulomas in an immunocompromised HIV-negative patient.

Disseminated cryptococcosis usually occurs in immunocompromised individuals with defective cell-mediated immunity, most commonly seen with HIV infection. We present a case of disseminated cryptococcosis in an HIV-negative male patient who presented with headache, fever, altered sensorium of short duration and multiple cutaneous lesions. An emergency CT scan of the head showed multiple intracranial and intraventricular granulomas. Routine laboratory investigations were within the normal range. A CSF examination revealed capsulated yeasts on India ink and a culture yielded cryptococcus neoformans. A cryptococcal antigen test by latex agglutination kit was positive. A biopsy revealed multiple capsulated yeasts cells in the cutaneous lesions, which were consistent with cryptococcus neoformans. The patient was successfully treated with Amphotericin B and Fluconazole with regression of cranial and cutaneous lesions.

Fatal cerebral abscess caused by Cladophialophora bantiana.

Primary cerebral phaeohyphomycosis is caused by pigmented fungi that exhibit distinct neurotropism often in immunocompetent individuals. A 20-yr-old male presented with multiple brain abscess which was subsequently proven microbiologically to be due to Cladophialophora Bantiana. In spite of near total excision and appropriate antifungal agents succumbed to his illness. We report this case to highlight its rarity and high mortality in an immunocompetent host. There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation.

Criptococosis cerebral en paciente con VIH: a propósito de un caso / Cerebral cryptococcosis in a patient with HIV: a purpose of a case

El agente Etiológico es el Criptococcus (Torulosis, blastomicosis europea) es una de las infecciones fúngicas más frecuentes del SNC. Es un hongo común en el suelo encontrado en los lugares de permanencia de los pájaros. La vía respiratoria es generalmente la puerta de entrada, menos frecuente es la piel y membranas mucosas. Los cambios patológicos son los de una meningitis granulomatosa; meningoencefalitis o como una masa. La diseminación es por vía hematógena. La meningitis es la presentación más frecuente en pacientes inmunocompetentes y la infección diseminada es más común en pacientes con SIDA. En este trabajo presentamos el caso clínico de un paciente masculino de 35 años, quien consultó cefalea holocraneana (frontal, parietal y occipital) de carácter pulsátil que lo incapacitó de tal forma no pudiendo realizar ninguna actividad ingirió AINES sin mejoría se acompañó de hipertermia no cuantificada los 1eros 5 días. Acompañándose de convulsiones tónico clónicas por lo que deciden realizar paraclínica y punción lumbar, donde se evidencia, serología reactiva para VIH. En la punción lumbar reportó: Cantidad: 3cc; Gram: no se observaron gérmenes; células: 0; glucosa: 64, Proteínas: 19; Pandy: negativo. Exámen directo: levaduras en gemación moderada; aspecto: turbio. En la tinción con tinta china: criptococcus neoformans. Posteriormente se incia tratamiento específico antifúngico con buena evolución y se inicia tratamiento antiretroviral luego que se confirma el diagnóstico de SIDA. Este es el primer caso reportado en nuestro estado Mérida en los últimos cuatro años, en pacientes inmunológicamente comprometidos con VIH.

Cerebral blastomycosis: a case report.

Blastomycosis is a chronic systemic fungal infection characteristically affecting the skin and lungs. Involvement of the central nervous system (CNS) is unusual, with cases generally presenting with meningitis, and rarely as intracranial mass lesion and solitary or multiple abscesses. Only two cases of intracranial extra-axial blastomycosis have been reported from India, and we report the third case, which presented as meningioma in a 23-year old female.

Paracoccidioidomicose do sistema nervoso central: análise de 13 casos / Central nervous system paracoccidioidomycosis: analysis os 13 cases

A paracoccidioidomicose (PCM) é infecção granulomatosa sistêmica, causada pelo fungo Paracoccidioides brasiliensis, prevalente na América Latina, particularmente no Brasil. Acomete o sistema nervoso central (SNC) em 10 por cento dos casos. Foram estudados 13 pacientes com paracoccidioidomicose no SNC, entre 1991 e 2001, com ênfase para os aspectos clínicos, neuroradiológicos e terapêuticos. Onze pacientes eram do sexo masculino (84,6 por cento) e dois do feminino (15,4 por cento), com idade entre 30 e 71 anos (M= 47,1 ± 11,6 Me= 46). Os sintomas mais freqüentes foram déficits motores (53,8 por cento), alterações cognitivas (53,8 por cento), emagrecimento (46,1 por cento), cefaléia (46,1 por cento) e crises convulsivas (46,1 por cento). O diagnóstico foi confirmado pela detecção do P. brasiliensis no SNC. Todos os pacientes apresentavam a forma granulomatosa e quatro (30,8 por cento) tinham a forma meningoencefalítica associada. Todos foram estudados com tomografia computadorizada (TC) de crânio e um caso com ressonância magnética (RM) encefálica. Dez pacientes (76,9 por cento) realizaram sorologia para o HIV, todos com resultados negativos. A anfotericina B foi utilizada em 12 casos (92,3 por cento), em um deles por via intratecal. Em oito casos (61,5 por cento) o sulfametoxazol-trimetropim foi utilizado; em dois (15,4 por cento) a sulfadiazina e pirimetamina, e o fluconazol, cetoconazol e itraconazol, cada um deles em um paciente. Seis pacientes (46,1 por cento) morreram e sete evoluíram satisfatoriamente. O tempo de seguimento variou de 2 a 74 meses (M=30,9). Conclui-se que as manifestações clínicas assim como os exames de imagem na PCM do SNC são inespecíficos.

Evolução incomum de provável histoplasmose de sistema nervoso central: de leptomeningite para granuloma da fossa posterior: Relato de caso com imagens por ressonância magnética / Uncommon evolution of probable central nervous system histoplasmosis: from leptomeningitis to posterior fossa granuloma: A case report with magnetic resonance images

Um caso de jovem paciente imunocompetente com provável histoplasmose do sistema nervoso central é aqui reportado, com ênfase nos aspectos evoluktivos muito peculiares de neuroimagem por ressonncia magnética que foram encontrados. Inicialmente foi observado espessamento leptomeníngeo, que, posteriormente, acabou organizando-se em granuloma de fossa posterior. O diagnóstico da infecção fúngica só foi obtido através do estudo histopatológico e o tratamento empregado baseou-se no uso do fluconazol em terapia de longo prazo, com boa resposta inicial.

We report a case of a young immunocompetent patient with probable central nervous system histoplasmosis with evolutive peculiar findings seen on magnetic resonance imaging. Leptomeningeal thickening was initially observed which subsequently became a posterior fossa granuloma. The diagnosis of fungal infection was only reached by histopathological study and the treatment was based on long term therapy with fluconazole with good initial response.

Multiple brain abscesses due to Penicillium spp infection

Apresentamos um caso de infecção do sistema nervoso central (SNC) por Penicillium spp em paciente do sexo masculino, HIV-negativo no Brasil. O paciente apresentou-se ao Serviço de Urgência do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo queixando-se de alteração visual e dificuldade na fala. Exames de neuroimagem mostraram lesões múltiplas, compatíveis com abscessos. A biópsia esterotáxica revelou infecção fúngica, iniciando-se o tratamento com anfotericina B com sucesso inicial. O paciente morreu poucos dias depois, vítima de uma hemorragia digestiva maciça devido a varizes de esôfago. A necropsia e a análise microbiológica final da biópsia cerebral revelaram infecção por Penicillium spp. Exixtem centenas de espécies de fungos do gênero Penicillium. A peniciliose sistêmica é causada pelo P. marneffei e costumava ser uma doença rara, mas atualmente é uma das infecções oportunistas mais comuns em associação com AIDS no Sudeste Asiático. Infecção pelo Penicillium spp de espécie diferente do P. marneffei normalmente causa apenas doenças superficiais ou alérgicas mas doenças invasivas também ocorrem raramente. Nós relatamos o quarto caso de infecção do SNC por Penicillium spp.

Central Nervous System Paracoccidioidomycosis: an overview

Paracoccidioidomycosis (PCM) is an infectious disease, endemic to subtropical areas of Central and South America, caused by the dimorphic fungus Paracoccidioides brasiliensis. It is a chronic disease, mostly affecting adult males, with a mean patient age of 44 years. Central nervous system involvement (CNS PCM) has been found in 13 percent of the patients with systemic disease. We reviewed the clinical presentation, diagnosis techniques and treatments for CNS PCM.

Aspergilloma of the brain: an overview.

Fungal infections of the central nervous system (CNS) are almost always a clinical surprise. Their presentation is subtle, often without any diagnostic characteristics, and they are frequently mistaken for tuberculous meningitis, pyogenic abscess, or brain tumor. Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Aspergillus fumigatus is the most common human pathogen in the genus Aspergillus. Maxillary sinusitis of dental origin or the lungs are the most common sites of primary Aspergillus infection. Infection reaches the brain directly from the nasal sinuses via vascular channels or is blood borne from the lungs and gastrointestinal tract. Single or multiple abscess formation with blood vessel invasion leading to thrombosis is a characteristic feature of Aspergillosis on neuropathologic examination. Aspergillosis should be considered in cases manifesting with acute onset of focal neurologic deficits resulting from a suspected vascular or space-occupying lesion especially in immunocompromised hosts. Aspergillosis is diagnosed on direct examinations and culture, however the diagnosis of aspergillosis of the CNS is difficult. Diagnosis of an intracranial mass lesion is best confirmed with a computed tomography or magnetic resonance imaging of the head with or without intravenous contrast. Aggressive neurosurgical intervention for surgical removal of Aspergillus abscesses, granulomas, and focally infracted brain; correction of underlying risk factors; Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. Off late Liposomal Amphotericin B was found to be more effective and safe than conventional Amphotericin B in the management of Apergillus infections Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this group of patients.