In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis

TOLL-LIKE RECEPTORS (TLR) 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS

There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections

Concomitant Lucio Phenomenon and Erythema Nodosum in a Leprosy Patient: Clues for Their Distinct Pathogeneses

Lepromatous leprosy patients may develop necrotic lesions, usually in the context of Lucio phenomenon (LP) or severe erythema nodosum (EN). The clinical and histopathological characteristics of the necrotic manifestations of both entities may eventually be confounded. We describe a patient with lepromatous leprosy who developed, since the 4th month of her first pregnancy, recurrent necrotic lesions in lower limbs, which, at the postpartum, worsened and led to partial destruction of ears and nose. In addition, she referred painful nodes oil upper limbs since I year before pregnancy and intermittent swelling and tenderness of the ankles, which together with a right tibial and ulnar neuritis led to the diagnosis of, erythema nodosum leprosum (ENL). The histopathology of a biopsy of the upper limb (ENL) revealed a dermal-hypodermal inflammation with vasculitis and vascular lumen narrowing, whereas biopsy of the lower limb (LP) revealed small vessels with fibrin thrombi on the superficial layer of the dermis without inflammatory infiltrate and no evidence of vasculitis. Thus, besides having several different clinical features, LP and ENL result from different pathogenetic mechanisms. The histopathological and clinical features distinguishing both entities are proposed. This distinction is important because decrease in bacillary load through multidrug therapy is the main target in LP, whereas in ENL, concomitant reduction of the reaction by means of thalidomide or high-dose steroids is recommended

TOLL-LIKE RECEPTORS (TLR) 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS

A literatura sobre o papel da resposta imune inata em dermatofitose é escassa. Este estudo se propôs a investigar a participação dos receptores do tipo Toll 2 e 4 (TLRs) 2 e 4 em pacientes com dermatofitose localizada (LD) e disseminada (DD, definida como lesões em pelo menos três segmentos corpóreos distintos), causadas por Trichophyton rubrum. Foram analisados cortes histológicos de 15 pacientes recém-diagnosticados, oito com LD e sete com DD. O grupo controle foi composto por 20 amostras de pele de indivíduos saudáveis submetidos a cirurgia plástica. TLR-2 e TLR-4 foram quantificados em lesões cutâneas por imunohistoquímica. Encontramos uma expressão reduzida de TLR-4 na epiderme superior e inferior nos dois grupos, LD e DD, quando comparados com o grupo controle; a expressão de TLR-2 foi preservada na epiderme superior e inferior de todos os três grupos. Como a sinalização por TLR-4 induz produção de citocinas inflamatórias e recrutamento de neutrófilos, a menor expressão desta molécula provavelmente contribui para a não resolução da infecção e conseqüente natureza persistente da dermatofitose. Como a sinalização via TLR-2 tem sido descrita como fator de regulação do processo inflamatório e de preservação da estrutura epidérmica, a sua expressão inalterada nas lesões dos pacientes com DD e DL pode contribuir também para a persistência da infecção e do reduzido processo inflamatório que são característicos das infecções por dermatófitos.There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections

A Patient with Erythema Nodosus Leprosum and Chagas Cardiopathy: Challenges in Patient Management and Review of the Literature

We report a patient with severe multi-bacillary leprosy complicated by recurrent episodes of erythema nodosum necrotisans that required thalidomide and/or corticosteroids during follow-up. Although the patient was from an area to which Chagas disease is endemic, this diagnosis was initially missed and was only investigated when heart failure developed in the patient. The difficulties of managing erythema nodosum necrotisans and heart failure concomitantly and those involved in excluding the diagnosis of acute myocarditis caused by reactivation of Chagas disease secondary to the immunosuppressive regimen are discussed. Other potential causes for the heart failure and possible interactions between the two diseases and their treatments are discussed. We also reviewed the literature for the association between leprosy and Chagas disease, both of which are highly endemic in Brazil. This case emphasizes the importance of searching for subclinical co-infections in leprosy patients because reactions frequently develop during specific treatment in these patients, and these reactions require prolonged therapy with immunosuppressive drugs

Vasculite cutânea de pequenos vasos: etiologia, patogênese, classificação e critérios diagnósticos - Parte I Small vessel cutaneous vasculitis: etiology, pathogenesis, classification and diagnostic criteria - Part I

Vasculite é a inflamação da parede dos vasos. Pode variar em gravidade desde doença autolimitada de um único órgão até doença grave com risco de morte por falência de múltiplos órgãos. Existem várias causas, embora só se apresente por poucos padrões histológicos de inflamação vascular. Vasos de qualquer tipo e em qualquer órgão podem ser afetados, resultando em ampla variedade de sinais e sintomas. Diferentes vasculites com apresentações clínicas indistinguíveis têm evolução e tratamento muito diferentes. Essa condição representa desafio para o médico, incluindo classificação, diagnóstico, exames laboratoriais pertinentes, tratamento e seguimento adequado. Neste artigo são revistos a classificação, a etiologia, a patogênese e os critérios diagnósticos das vasculites cutâneas.<br>Vasculitis is an inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple-organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have very different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, treatment, and the need for careful follow-up. This article reviews the classification, etiology, pathology and diagnostic criteria of cutaneous vasculitis