The natural history of gluten sensitivity: Report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives

OBJECTIVE: Early studies revealed that up to 50% of nonatrophic, first-degr ee relatives of celiac disease patients exhibit features of gluten sensitiv ity. However, whether these features progress to a fully expressed celiac d isease remain partially known. Our aim was to report two new patients resul ting from a prospective, long-term surveillance of relatives who were nonat rophic at initial assessment. METHODS: After a median time of 86 months (range: 42-102 months) from the b aseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte in filtration, and 23 did not. In addition, 11 of 18 had a celiac-like respons e to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-rela ted serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positiv e subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Hi stological examination revealed flat small bowel mucosa in both. At baselin e, both cases were EmA-negative and no minor histological changes were obse rved. One was a woman with positive baseline IgA and IgG AGA and a rectal g luten challenge with a celiac-like response; the other patient has presente d only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA D Q2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have be en negative on initial screening for celiac disease. Up to now, the progres sion to severe enteropathy was only observed. in relatives who had presente d some evidence of gluten sensitivity and the characteristic KLA DQ2 haplot ype. Longer longitudinal studies are necessary to obtain definitive conclus ions. (C) 2000 by Am. Cell. of Gastroenterology.