Lúcia M. S Azevedo

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases.

Search for evidence of a Th2 profile in HIV+ patients

Background Hypersensitivity dermatoses are common in human immunodeficiency virus‐positive (HIV+) patients, particularly as the disease progresses. Studies have shown that a switch to T‐helper 2 (Th2) might represent a turning point in HIV. This study investigated whether increases in the number of skin mast cells, immunoglobulin E (IgE) serum levels, and eosinophilia, involved in the Th2 response in allergic disease, might also be present in HIV+ patients. If so, these alterations might explain one of the mechanisms of skin hypersensitivity in these patients.

Carcinoma epidermoide do pênis: estudo clínico-patológico de 34 casos

FUNDAMENTOS: No Brasil, a incidencia do câncer do penis e de 8,3 casos/100.000 habitantes, contrastando com 0,7 na Europa e nos Estados Unidos. Em 95% dos casos, trata-se do carcinoma epidermoide. Em geral, e diagnosticado tardiamente. OBJETIVOS: Descrever as caracteristicas clinico-patologicas do carcinoma epidermoide do penis, registradas no Hospital entre 1978 e 2004. METODOS: Estudo observacional transversal. Incluiram-se os casos de carcinoma epidermoide do penis, confirmados histologicamente. Avaliaram-se, pessoalmente, os pacientes que atenderam a convocacao para o estudo, enquanto os demais tiveram seus dados pesquisados nos prontuarios medicos. RESULTADOS: Registraram-se 34 pacientes com carcinoma epidermoide do penis: 8 in situ e 26 invasivos, com idade media de 54,7 12,5 anos, respectivamente. A± 22,4 e 64,7 ±, a glande foi acometida em 91,1% dos casos e o prepucio, em 41,1%. Os carcinomas epidermoides in situ exibiam papulas ou eritema e erosao, geralmente menores do que 2 cm. Os invasivos mostravam ulceras e/ou vegetacoes, geralmente unicas, e maiores do que 2 cm. Dos CE invasivos, 80,8% eram bem diferenciados; metade encontrava-se no estagio I TNM e o restante, do II ao IV; 16 pacientes tiveram o penis amputado e 3 faleceram. CONCLUSOES: O câncer do penis e raro, acomete adultos de todas as faixas etarias e o tratamento pode ser agressivo. O aspecto clinico inespecifico das lesoes iniciais, o insuficiente treinamento medico em lesoes dermatologicas e a carencia de rotinas de investigacao diagnostica, tratamento e acompanhamento destes casos contribuem para o mau prognostico desta neoplasia.

Normal skin of HIV-infected individuals contains increased numbers of dermal CD8 T cells and normal numbers of Langerhans cells

Dysregulation of the skin immune system (SIS) could explain the high prevalence of skin disorders in HIV+ individuals. The present study was carried out to determine whether alterations in the cell population of SIS and epidermal immunoactivation occur in the normal skin of HIV+ individuals. Forty-five biopsies were taken from the normal upper arm skin of 45 HIV+ patients and of 15 healthy controls. HIV+ individuals were divided into three categories according to their CD4 cell blood count (<200, 200-499 and > or = 500/microl). Hematoxylin-eosin was used to stain tissue sections for morphological analysis and immunohistochemistry was used for the evaluation of the frequency of macrophages, Langerhans cells, and CD lymphocyte subsets. In addition, semiquantitative analysis of LFA-1, ICAM-1 and HLA-DR was determined in epidermal cells. Macrophages, Langerhans cells, and CD lymphocyte subsets did not differ significantly between any of the patient categories and the control group. When all HIV+ individuals were compared as a group to the control group, a significant increase in dermal CD8+ T lymphocytes (P < 0.01) and lower CD4-CD8 ratios (P < 0.01) were observed in the HIV+ individuals. Epidermal ICAM-1 and HLA-DR expression was negative in both HIV+ and normal skin biopsies. No evidence of a depletion of the SIS population or of epidermal immunoactivation in normal skin from HIV+ individuals was demonstrable, suggesting that alterations in the central immune system are not necessarily reflected in the SIS of HIV-infected patients.

HLA-Marker bei familiärem Lichen sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families, often associated with HLA markers, mainly DQ7. A genetic co-etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti-thyroid peroxidase autoantibodies (anti-TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR-SSP, and measurement of anti-TPO, free thyroxine and thyroid-stimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti-TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*.The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS.The presence of anti-TPO antibodies strongly suggests autoimmune thyroiditis. There is intra-familial association between the haplotype HLA-B*15 -DRB1*04 -DRB4* and anti-TPO, emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.

Decorina e Condroitim sulfato na remodelação da matriz extracelular do línquen escleroso vulvar

FUNDAMENTOS: O liquen escleroso (LS) apresenta zona de hialinizacao do colageno na derme superior caracteristica, que persiste pouco definida do ponto de vista morfologico e cujo significado permanece sem explicacao. Ja se pode demonstrar que no LS ha profundas modificacoes da matriz extracelular (MEC), com acumulo de proteinas colagenicas e de glicosaminoglicanos sulfatados na regiao hialina. OBJETIVOS: Caracterizar morfologicamente a presenca nessa zona de decorina e condroitim sulfato que, ao interagir com as fibrilas colagenas, entre outras proteinas matriciais, poderiam contribuir para essa peculiar apresentacao da MEC. METODOS: 31 casos de LS vulvar foram subdivididos segundo a gradacao histologica de Hewitt e analisados por imuno-histoquimica utilizando anticorpos contra decorina e condroitim sulfato revelados pela diaminobenzidina. Esses resultados foram comparados aos do grupo controle constituido por fragmentos de retalhos cutâneos excisados durante cirurgias corretivas da regiao vulvoperineal. RESULTADOS: Ocorreu predominio da decorina quando a matriz apresentava um aspecto frouxo/edematoso, e o condroitim sulfato foi mais evidente quando a MEC assumia um padrao compacto, parecendo que ambos contribuem para o aspecto hialino, porem em fases diferentes da patogenia dessa doenca. CONCLUSOES: A sequencia observada na sintese desses proteoglicanos/glicosaminoglicanos levou a suposicao de que a decorina seja um possivel marcador precoce do LS vulvar e de que o condroitim sulfato possa estar relacionado a contencao da alteracao matricial no nivel da derme media.