ABSTRACT Visceral leishmaniasis (VL) is mainly caused by Leishmania (Leishmania) donovani and Leishmania (L.) infantum; however, other Leishmania species have been associated with VL. We report a case of a patient simultaneously diagnosed with VL caused by Leishmania (L.) amazonensis and Hodgkin’s lymphoma. After treatment with liposomal amphotericin B and chemotherapy, the patient presented a clinical cure. This case report reinforces the hypothesis that other Leishmania species can cause visceral lesions mainly related to immunosuppression.

Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

ABSTRACT Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

RESUMO A região parietooccipital é mais frequente e gravemente acometida na panencefalite esclerosante subaguda (PEESA). Os gânglios da base, cerebelo e corpo caloso são menos envolvidos. Descrevemos um paciente com PEESA confirmada por neuropatologia com imagens de ressonância magnética (RNM) evidenciando acometimento extenso dos gânglios da base sem envolvimento de outras estruturas corticais. Embora raramente descritas nesta doença, deve-se ficar atento para tal acometimento e PEESA deve ser lembrada quando alterações de sinal nos gânglios da base são vistas na RNM com ou sem acometimento de outras regiões do cérebro a fim de evitar outros diagnósticos etiológicos errôneos de patologias que cursam com demência rapidamente progressiva.

ABSTRACT The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe a patient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia.

OBJETIVOS: O objetivo deste estudo foi descrever o padrão de expressão dos receptores toll-like 2 e 4 (TLR2 e TLR4) em biópsias de pele de pacientes com leishmaniose tegumentar americana (LTA). MÉTODOS: Este estudo prospectivo avaliou 12 pacientes com LTA causada por Leishmania braziliensis confirmada por reação em cadeia da polimerase. Imunohistoquímica foi realizada para determinar a expressão de TLR2 e TLR4. O número de células NK, células dendríticas e macrófagos foi calculado no tecido. A expressão de citocinas foi determinada usando anti-TNF-α, anti-IFN-Γ, anti-IL-1 e anti-IL-6. Dupla marcação foi usada para determinar a célula responsável pela expressão de TLR2 e TLR4. RESULTADOS: O número de células expressando TLR2 e TLR4 foi 145.48±82.46 cell/mm² e 3.26 ± 4.11 cell/mm² respectivamente (p < 0.05). Não houve correlação entre a quantidade de expressão de TLR2 e TLR4 com a quantidade de citocinas e o número de células NK, macrófagos e células dendríticas. A dupla marcação revelou que o TLR2 é expresso por macrófagos. CONCLUSÃO: Na LTA causada por Leishmania braziliensis, TLR2 é o TLR mais comum na doença ativa, principalmente por macrófagos sem correlação com a quantidade de citocinas e outras células.

OBJECTIVES: The aim of this study was to describe the pattern of expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in skin biopsies of patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. METHODS: This prospective study evaluated 12 patients with ATL caused by Leishmania braziliensis confirmed by polymerase chain reaction. Immunohistochemistry was performed to determine the expression of TLR2 and TLR4. The number of NK cells, dendritic cells and macrophages in the tissue were calculated. The cytokine expression was determined using the anti-TNF-α, anti-IFN-Γ, anti-IL-1 and anti-IL-6. Double immunostaining reactions were used to determine the cell expressing TLR2 and TLR4. RESULTS: The numbers of cells expressing TLR2 and TLR4 were 145.48 ± 82.46 cell/mm² and 3.26 ± 4.11 cell/mm² respectively (p < 0.05). There was no correlation of TLR2 and TLR4 with the amount of cytokines and the number of NK cells, dendritic cells or macrophages. The double immunostaining revealed that TLR2 was expressed by macrophages. CONCLUSION: In human cutaneous leishmaniasis caused by Leishmania braziliensis, TLR2 is the most common TLR expressed during active disease, mainly by macrophages although without correlation with the amount of cytokines and number of cells.

Sarcoidosis has been rarely described in literature as a cause of interstitial pulmonary disease associated with AIDS. This study reports a case of immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in a patient with a history of previous pulmonary tuberculosis concomitant with HIV infection. Results of the immunohistochemical study of samples from the resected right lower lobe are described. Pathological findings suggest a role of Th1, Th2 and Th17 response in IRIS associated sarcoidosis.

INTRODUÇÃO: Leishmaniose visceral (LV) é uma doença tropical negligenciada com uma resposta imune complexa em diferentes órgãos. Este padrão de resposta imune órgão-específica nunca foi avaliada no trato gastrointestinal. O objetivo deste estudo foi determinar a resposta imune in situ em biópsias duodenais de pacientes com LV. MÉTODOS: Um estudo de caso controle com 13 pacientes com LV foi comparado com 9 controles. A resposta imune foi avaliada por imunohistoquímica para CD4, CD8, CD68, IL-4, IFN-γ, TNF-α e IL-10. Achados histológicos nos vilos, criptas e processo inflamatório foram analisados. RESULTADOS: Todos os casos de LV apresentaram antígenos de Leishmania. Nenhum antígeno foi encontrado no grupo controle. O tamanho do vilo foi maior em pacientes com LV (p < 0,05). CD68 (macrófagos) e CD4 estavam aumentados em pacientes com LV (p < 0,05). Nenhuma diferença foi demonstrada na expressão de CD8, TNF-α, IL-10 e IL-4. O número de células expressando IFN-γ foi mais baixo que no grupo controle (p < 0,05). CONCLUSÕES: Baixos níveis de citocinas foram encontrados no trato gastrointestinal de pacientes com LV. Este padrão não foi encontrado em outros órgãos acometidos pela doença. Uma imunotolerância do tecido contra Leishmania poderia explicar estes achados, como ocorre com as bactérias entéricas.

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2). A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e a gamaglutamiltranspeptidase foram mais altas no grupo VHC. Não houve diferença entre os grupos à análise histopatológica do fígado. Por análise discriminante definiram-se funções classificatórias, incluindo as variáveis sexo, faixa etária, uso de drogas endovenosas e parceiro sexual com hepatite, com acurácia discriminante alta para o grupo VHC.

Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2). The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.

INTRODUÇÃO: A patogênese da hepatite C crônica ainda está em discussão. Sabe-se que linfócitos T (LT) CD4+ e CD8+ são tipicamente observados no espaço portal e peri-portal de pacientes com hepatite C crônica, mas o conhecimento exato de suas ações no fígado, bem como sua influência na progressão da doença hepática ainda estão em discussão. MÉTODOS: Os LT CD4+ e T CD8+ foram quantificados por imunohistoquímica nos espaços porta e peri-portais em 39 biópsias hepáticas de pacientes cronicamente infectados pelo vírus da hepatite C. Esses dados foram associados com os dados demográficos, as alterações histológicas, os achados laboratoriais dos pacientes com hepatite C e com os genótipos do vírus da hepatite C. RESULTADOS: Houve grande quantidade tanto de LT CD4+ como de CD8+, sendo que houve maior densidade de LTCD4+ do que CD8+ nos espaços portal e peri-portal. Tanto o número de linfócitos T CD4+ como de CD8+ foram diretamente relacionados com a intensidade da hepatite de interface. Os linfócitos T CD8+ foram estatisticamente relacionados às enzimas hepáticas. CONCLUSÃO: O encontro de numerosos linfócitos T CD4+ e linfócitos T CD8+ no espaço-portal e peri-portal e sua correlação com a hepatite de interface sugerem que a evolução da hepatite C dependa da ação dos linfócitos T intra-hepáticos, ou seja, há um mecanismo imuno-mediado na patogênese da hepatite C crônica.

BACKGROUND: The pathogenesis of chronic hepatitis C is still a matter of debate. CD4+ and CD8+ T lymphocytes (TL) are typically observed within the portal and periportal spaces of affected livers, but their functional role in hepatitis C progression has not been fully elucidated. METHODS: CD4+ and CD8+ TL were quantified by immunohistochemistry in portal and periportal spaces of 39 liver biopsies from patients with chronic hepatitis C. They were associated to demographic data, histological parameters, laboratory findings of patients and hepatitis C genotypes. RESULTS: There was high numbers of CD4+ and CD8+ TL from which the density of CD4+ T was higher than CD8+ TL in portal and periportal spaces. CD4+ and CD8+ TL were directly correlated to intensity of interface hepatitis. CD8+ TL correlated to serum enzyme levels. CONCLUSION: The high numbers of CD4+ and CD8+ TL in portal and periportal spaces and their correlation to interface hepatitis suggest that hepatitis C evolution depends on the action of intrahepatic T lymphocytes, lending support to the notion of an immune-mediated mechanism in the pathogenesis of chronic hepatitis C.

OBJETIVO: Trabalhos experimentais demonstram que as defesas do hospedeiro frente ao Pneumocystis carinii incluem interações complexas entre as células imunes, principalmente linfócitos TCD4+ e macrófagos alveolares. Sendo esse um agente importante associado às imunodeficiências, nosso objetivo foi caracterizar a resposta inflamatória em pulmão de necrópsias de pacientes com AIDS. MÉTODOS: Foram selecionadas 25 necrópsias com diagnóstico de pneumonia por Pneumocystis carinii para pesquisa imuno-histoquímica de linfócitos TCD4+, TCD8+, macrófagos CD68+, células NK CD57+ e células com expressão de TNF-alfa. As células imunomarcadas foram quantificadas e analisadas estatisticamente. RESULTADOS: Todos os espécimes evidenciaram elevado parasitismo na luz dos alvéolos. Observou-se espessamento septal com infiltrado inflamatório constituído predominantemente por linfócitos e macrófagos. Houve diminuição no número de linfócitos TCD4+ e aumento de linfócitos TCD8+, macrófagos e células NK. No septo alveolar freqüentemente observaram-se células expressando TNF-alfa. CONCLUSÕES: A imunossupressão relacionada à AIDS induz a diminuição de linfócitos TCD4+ e favorece a permanência de elevado parasitismo. Os componentes celulares que caracterizam o infiltrado inflamatório contribuem para os danos irreversíveis no pulmão desses pacientes.

OBJECTIVES: It has been experimentally demonstrated that host defense against Pneumocystis carinii depends on complex interactions within host immune response, mainly CD4 lymphocytes and alveolar macrophages. Since this is an important agent related to immunodeficiency, our purpose was to characterize the inflammatory immune response in lung from necropsy of AIDS patients. PROCEDURES: Twenty-five necropsies with diagnosis of Pneumocystis carinii pneumonia were selected for immunohistochemical investigation of CD4 and CD8 lymphocytes, macrophages (CD68+), NK cells (CD57+) and cells expressing TNF-alpha. The immunostained cells were quantified and statistically analyzed. RESULTS: All specimens presented a great number of cysts of Pneumocystis carinii in alveoli, as well as septal enlargement with inflammatory infiltrate constituted predominantly by lymphocytes and macrophages. CD4+ T cells were decreased in number, and CD8+ T cells, NK cells and macrophages predominated. Cells expressing TNF-alpha were frequently observed in septal inflammatory infiltrate. CONCLUSIONS: The immunosupression related to AIDS induces a reduction in the number of CD4+ T cells and influences high-level parasitism. The cell components that characterize the inflammatory infiltrate contribute to the severe lung injury of those patients.

O presente caso ilustra uma forma de eritema nodoso, cujo agente foi o Trypanosoma cruzi em paciente chagásica submetida a transplante cardíaco. O diagnóstico foi firmado através do exame histopatológico de biópsia da lesão cutânea e estudo imunohistoquímico. O tratamento com nifurtimox promoveu regressão total das lesões.

We report a patient with Chagas' disease that presented Trypanosoma cruzi reactivation after cardiac transplantation and immunodepression, characterized by skin lesions of erythema nodosum. This is an unusual presentation of Chagas' disease.

O comprometimento do trato gastrointestinal é uma manifestação incomum da co-infecção HIV-Leishmaniose Visceral (LV). Descreveremos o primeiro caso de comprometimento pancreático por LV disseminada na AIDS, como primeira manifestação oportunista (além do comprometimento do figado, baço, linfonodos e rins). A necropsia revelou pâncreas normal ao exame macroscópico. A microscopia ótica do pâncreas revelou: atrofia pancreática severa, diminuição dos grânulos de zimogênio, anormalidades nucleares discretas e presença de formas amastigotas de Leishmania em macrófagos intersticiais, além do antígeno da LV e HIV-p24 (imunohistoquímica-IH). À microscopia eletrônica: pâncreas com grânulos de zimogênio diminuídos, proliferação do retículo granuloso, mitocôndrias aumentadas, evidenciando o aspecto já observado por nós em pâncreas de pacientes com AIDS sem LV. Presença de formas amastigotas da Leishmania no fígado, baço, linfonodos além do antígeno da LV no rim (IH). As alterações histológicas pancreáticas são sugestivas de desnutrição protéico calórica, que pode estar representada neste caso pela desnutrição induzida pela cirrose, pela leishmaniose ou pela AIDS. Acreditamos ser esse último o principal responsável pelas alterações histológicas encontradas. No entanto estudos futuros são necessários para elucidar esses achados.

The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.

A transmissão congênita da doença de Chagas continua a ser um problema no Brasil. Em um estudo com 58 recém-nascidos, de 57 mães com a forma crônica da doença de Chagas, selecionadas em três Instituições de Saúde da Cidade de São Paulo, a transmissão congênita foi demonstrada em 5,17% (3/58) dos casos, com um provável caso confirmado somente pelo achado de antígenos do T. cruzi na placenta e cordão umbilical. Os testes parasitológicos (microhematócrito, quantitative buffy coat-QBC ou xenodiagnóstico artificial) foram capazes de diagnosticar dois casos congênitos de infecção pelo T. cruzi, nascidos de mulheres chagásicas com infecção pelo HIV. A imunohistoquímica efetuada nestas duas placentas foi capaz de identificar formas amastigotas e antígenos do T. cruzi. A infecção congênita foi confirmada a nível placentário em outros dois casos, e a nível fetal em um destes casos por imunohistoquímica. O Immunoblotting utilizando antígenos excretados/secretados de formas tripomastigotas do T. cruzi (TESA-blot), detectou anticorpos IgG em 54/55 dos casos e IgM em 1/55. Nos dois casos congênitos um apresentou anticorpos IgG e IgM o no outro não foram detectados anticorpos IgG ou IgM anti T. cruzi, apesar do achado de parasitas circulantes.

The congenital transmission of Chagas’ disease was evaluated in 57 pregnant women with Chagas’ disease and their 58 offspring. The patients were selected from three Health Institutions in São Paulo City. The maternal clinical forms of Chagas’ disease were: indeterminate (47.4%), cardiac (43.8%) and digestive (8.8%); 55 were born in endemic areas and two in São Paulo City. The transmission of Chagas’ disease at fetal level was confirmed in three (5.17%) of the 58 cases studied and one probably case of congenital Chagas’ disease. Two infected infants were born to chagasic women with HIV infection and were diagnosed by parasitolological assays (microhematocrit, quantitative buffy coat-QBC or artificial xenodiagnosis). In both cases the placenta revealed T. cruzi and HIV p24 antigens detected by immunohistochemistry. In one case, a 14-week old abortus, the diagnosis of congenital T. cruzi infection was confirmed by immunohistochemistry. The other probable infection, a 30-week old stillborn, the parasites were found in the placenta and umbilical cord. The Western blot method using trypomastigote excreted/secreted antigens of T. cruzi (TESA) was positive for IgG antibodies in 54/55 newborns and for IgM in 1/55 newborns. One of the two newborns with circulating parasites had no detectable IgG or IgM antibodies. The assessment of IgG antibodies in the sera of pregnant women and their newborns was performed by ELISA using two different T. cruzi antigens: an alkaline extract of epimastigotes (EAE) and trypomastigote excreted/secreted antigens (TESA). The analysis showed a linear correlation between maternal and newborn IgG antibody titers at birth.

Paciente com doença de Chagas, em fase crônica, após ter sido submetida a transplante de rim sofreu reativação da infecção devido ao Trypanosoma cruzi, como conseqüência de imunodepressão medicamentosa. O acontecimento manifestou-se exclusivamente através de lesões cutâneas ulceradas, merecendo portanto divulgação tal aspecto clínico inusitado.

We report a patient with chronic asymptomatic Chagas' disease that presented Trypanosoma cruzi reactivation after kidney transplantation and immune depression. The only clinical manifestation of the disease was ulcerative skin lesions, wich is unusual in Chagas' disease.