clobetasol and Celiac-Disease

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

Topics: Administration, Topical; Autoantibodies; Celiac Disease; Clobetasol; Dapsone; Dermatitis Herpetiformis; Diet, Gluten-Free; GTP-Binding Proteins; HLA-DQ Antigens; Humans; Immunoglobulin A; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases

10 patients with sub-total villous atrophy were given the topical corticosteroids betamethasone valerate or clobetasone butyrate for a period of 4 months whilst continuing on a normal diet. 5 patients improved symptomatically while red cell folate, urinary xylose and faecal fat excretion also improved. Brush border enzymes increased in patients treated with higher dosages of each drug. Enterocyte height increased and intra-epithelial lymphocytes were significantly decreased although overall morphological appearances remained indistinguishable from untreated coeliac disease. Suppression of the pituitary adrenal axis occurred in 8 patients and there did not appear to be useful separation of topical from systemic activity. These compounds offer no advantage over prednisolone in non-responsive coeliac disease.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Betamethasone; Betamethasone Valerate; Celiac Disease; Clinical Trials as Topic; Clobetasol; Female; Humans; Male; Middle Aged; Patient Compliance; Prednisolone

The effect of the topical corticosteroid clobetasone butyrate on enzyme activity and morphology of duodenal mucosa was studied in 9 patients with coeliac disease and 10 controls using organ culture techniques. There was significant increase in mucosal alkaline phosphatase, lactase and maltase activities, but inclusion of a soluble extract of gluten reduced this effect. When clobetasone butyrate was also included in the culture medium significant elevations in enzymes were again observed. Enterocyte height was not affected by incorporation of gluten into the medium. Intra-epithelial lymphocyte counts fell significantly during the culture period. This improvement was also inhibited by gluten and overcome by addition of steroid.

Topics: Adult; Alkaline Phosphatase; alpha-Glucosidases; beta-Galactosidase; Betamethasone; Celiac Disease; Clobetasol; Culture Media; Humans; Intestinal Mucosa; Jejunum; Organ Culture Techniques