Increased Langerhans cell accumulation after mycobacterial stimuli.

AIMS: To evaluate the role of Langerhans cells (LCs) in the local activation of leprosy lesions. LCs, acting as tolerance inducers and immune stimuli, are dendritic cells recently implicated in cutaneous homeostasis. The role of LCs in the defence against mycobacterial infection remains poorly understood. METHODS AND RESULTS: The number and distribution of CD1a+ skin cells and HLA-DR and intercellular adhesion molecule (ICAM)-1 expression were analysed in leprosy skin lesions and in delayed-type hypersensitivity (DTH) tests. The results showed a high number of LCs in tuberculin and lepromin tests, in tuberculoid lesions and in the epidermis and dermis during type I and II reactions. In multibacillary lesions, however, the number of LCs was consistently low in comparison with other groups. Increased numbers of LCs were accompanied by marked HLA-DR and ICAM-1 expression, suggesting a strong relationship between these immunological events. CONCLUSIONS: CD1a+ cells are implicated in the local immunological events taking place after mycobacterial stimuli and may account for the local activation of all types of reactional episodes in leprosy.

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 500/æl). 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.

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.

Incidence of enteropathy-associated T-cell lymphoma in celiac disease: implications for children and adolescents with type 1 diabetes.

The long-term consequences of screening for celiac disease in diabetic children are not known. Routine screening is not practiced in our pediatric diabetic population. This study of the incidence of the most severe and specific long-term complication of untreated celiac disease, i.e., enteropathy-associated T-cell lymphoma (EATCL) and its association with diabetes, is done in order to justify our strategy not to practice routine screening. In the first phase of this study, a questionnaire was sent to all Swiss pathologists. The second phase consisted of a search in the cancer registry of the canton of Zurich. The incidence of EATCL in the general population of a Swiss region and the theoretical risk for a diabetic patient to develop this type of lymphoma were calculated. Ten cases of EATCL were found. Five had a long history of malabsorption, three of them since childhood. The mean age of the patients was 61.9 yr. None suffered from diabetes mellitus. The incidence of EATCL was 0.07/100,000 inhabitants/year. The expected risk for EATCL in patients with type 1 diabetes is 12.4/100,000 diabetic patients over a period of 60 yr. The data suggest that the risk for EATCL is small in diabetic patients. Therefore, we restrict the investigation for celiac disease to patients with typical and atypical symptoms, but do not perform routine screening.

Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.

Over the last 20 yr, 245 patients with chronic pancreatitis (163 with alcoholic relapsing pancreatitis; 145 of them with calcific pancreatitis) were prospectively studied at regular intervals with particular regard to pain, pancreatic functions, calcifications, pancreatic surgery, and survival. The median period of observation in the group with alcoholic relapsing calcific pancreatitis was 10.4 yr. In this group of 145 patients, 85% experienced lasting pain relief within a median time of 4.5 yr from onset. A gradual increase of pancreatic calcifications and pancreatic dysfunction was observed with increasing duration of the disease. Pain relief was accompanied by a marked increase in pancreatic dysfunction and calcification. Of 163 patients with alcoholic relapsing pancreatitis, 87 (53%) needed no pancreatic surgery. Seventy-six patients (47%) with recurrent or persistent severe pain, mainly due to pseudocysts (n = 56), underwent either a cyst drainage procedure (n = 22), papillotomy (n = 4), distal pancreatectomy (40%-60%, n = 24), or Wirsungo-jejunostomy (n = 26). The proportion of patients experiencing lasting pain relief was similar in the operated and nonoperated group of patients. In both groups lasting relief from pain was correlated with the duration of the disease and was associated with marked pancreatic dysfunction. The 50% survival time in alcoholic chronic pancreatitis (with or without pancreatic surgery) was 20-24 yr (after onset), thus markedly shorter than in nonalcoholic pancreatitis. Of the 245 patients, 86 died. About 20% of deaths were related to pancreatitis and its complications. Most extrapancreatic causes of death were malignancies, cardiovascular diseases, severe infections, and nonpancreatic surgery.