ABSTRACT
Abstract Background: The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new therapies. Objective: Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens. Methods: The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome. Results: A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment. Study limitations: Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ. Conclusions: The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.
Subject(s)
Humans , Leishmaniasis, Cutaneous/drug therapy , CD4-Positive T-Lymphocytes , Treatment Outcome , CD8-Positive T-Lymphocytes , Meglumine AntimoniateABSTRACT
Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Inflammation/immunology , Leishmaniasis, Cutaneous/immunology , Antigens, CD/immunology , /immunology , Antigens, Differentiation, Myelomonocytic/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Biopsy , /immunology , Chronic Disease , Disease Progression , Inflammation/pathology , Leishmaniasis, Cutaneous/pathology , Macrophages/immunology , Macrophages/pathology , von Willebrand Factor/immunologyABSTRACT
O episódio reacional tipo 1 ou reação reversa é ocorrência inflamatória aguda que atinge a pele e nervos periféricos, encontrada em até 30 por cento dos pacientes com hanseníase, sendo causa comum de incapacidade física. Fatores de risco associados incluem uso de poliquimioterapia e infecções virais. Neste estudo, foram avaliados 620 pacientes com hanseníase. Reação reversa foi diagnosticada em 121 (19,5 por cento) casos, sendo mais freqüente nos indivíduos borderlines (48 por cento). Início da poliquimioterapia foi considerado fator de risco para reação reversa, com 52 por cento dos casos apresentando o primeiro episódio neste momento. Neurite foi documentada em 73 por cento dos casos. A presença de vírus B ou C da hepatite foi documentada em 9 por cento de 55 pacientes com reação reversa e em nenhum dos 57 pacientes sem reação (p = 0, 026; teste exato de Fisher), sugerindo possível papel destes agentes como fatores de risco para desenvolvimento de reação reversa na hanseníase.
Type 1 reaction or reversal reaction is an acute inflammatory episode in the skin and peripheral nerves that is found in up to 30 percent of leprosy patients and commonly causes physical disabilities. Multidrug chemotherapy and viral infections are associated risk factors. In this study, 620 leprosy patients were evaluated. Reversal reactions were diagnosed in 121 cases (19.5 percent) and were most frequently found in borderline patients (48 percent). Starting on multidrug chemotherapy was considered to be a risk factor for reversal reaction: 52 percent of the cases presented their first episode at this time. Neuritis was found in 73 percent of the cases. The presence of hepatitis B or C virus was documented in 9 percent of the 55 patients with reversal reaction, while it was not detected in any of the 57 patients without reaction (p = 0.026, Fishers exact test). This suggests that these agents may have a role as risk factors for developing reversal reactions.
Subject(s)
Adult , Female , Humans , Male , Acute-Phase Reaction/etiology , Hepatitis B/complications , Hepatitis C/complications , Leprostatic Agents/administration & dosage , Leprosy/complications , Acute-Phase Reaction/diagnosis , Case-Control Studies , Hepatitis B/diagnosis , Hepatitis C/diagnosis , Leprostatic Agents/adverse effects , Leprosy/drug therapy , Retrospective Studies , Risk FactorsABSTRACT
O conhecimento dos principais mecanismos de defesa imune contra os diversos agentes infecciosos permite a compreensão da patogênese das doenças infectoparasitárias e das várias estratégias do hospedeiro e do parasita. O sistema imunológico atua numa rede de cooperação, envolvendo a participação de muitos componentes estruturais, moleculares e celulares. Nesse cenário encontra-se o delicado equilíbrio entre a saúde e a doença, em que tanto a deficiência quanto o exagero resultam em dano tecidual. Este artigo explora esses aspectos e algumas abordagens terapêuticas que surgem desse entendimento.