Celiac Disease - NIH Consensus Development Program - National ...

Skin Manifestations of Celiac DiseaseJohn J. Zone, M.D.Dermatitis herpetiformis (DH) is a cutaneous manifestation of celiac disease (CD). Thespectrum of intestinal abnormalities in DH ranges from minimal lymphocyte infiltration of thesmall intestinal epithelium in some patients to complete villous atrophy in others. Only about20 percent of DH patients have intestinal symptoms of CD. Both the skin disease and theintestinal disease respond to gluten restriction and recur with institution of a gluten-containingdiet. It seems likely that the presence of skin disease in DH patients is a marker of CD that isindependent of the severity of the histological CD or the severity of intestinal symptoms. Thecomplications and course of CD, as manifested in DH patients, may represent the true spectrumof CD that would otherwise largely go undiagnosed. Study of DH therefore gives insight into thenature of the spectrum of CD. For this reason, I will review the consensus questions relative toDH and will propose that understanding DH holds the potential to a better understanding of theentire spectrum of CD. (1)How is DH Diagnosed?Three findings support the diagnosis of DH: (1) pruritic papulovesicles on extensorsurfaces; (2) neutrophilic infiltration of the dermal papillae with vesicle formation at thedermal-epidermal junction; and (3) granular deposition of IgA in the dermal papillae of clinicallynormal-appearing skin adjacent to a lesion. The last finding is present in greater than 98 percentof DH patients and is the gold standard for diagnosis. (2) IgA tissue transglutaminase and IgAendomysial antibodies are found in 70–90 percent of patients, indicating that there is apopulation of CD patients who are negative for this serum antibody. IgA antibodies to epidermaltransglutaminase have been proposed as the causative antibody in DH. (3)How Prevalent is DH?DH is most common in those of northern European descent. It is exceedingly uncommonin African Americans and Asians. According to a study in Finland in 1978, the prevalence of DHis 10.4 per 100,000 and the incidence is 1.3 per 100,000. The mean age of onset was in the fourthdecade, but ranged from age 2 to 90. Adolescent and prepubescent children are infrequentlyaffected. This later age of onset is believed to indicate a need for chronic stimulation of themucosal immune system for production of the immune response that causes DH. In contrast toCD in the absence of DH, males outnumbered females 2:1. (4) From 1979 to 1996, the familialincidence of DH was studied prospectively in Finland. DH was diagnosed in 1,018 patients.10.5 percent of patients with DH had one or more affected first-degree relatives. (5)Studies in Utah confirm that DH and familial DH in the United States are of comparableprevalence to European studies. A study of a Utah population reflects the predominant northernEuropean ancestry in that area of the United States. The prevalence of DH in 1987 was 11.2 per100,000. The incidence for the years 1978–1987 was 0.98 per 100,000 per year. The mean age ofonset for males was 40.1 years. The mean age of onset for females was 36.2 years. The male to73