Coeliac disease screening in first-degree relatives on the basis of biopsy and genetic risk

BACKGROUND: Serological markers of coeliac disease (CD) lack diagnostic value to identify mild histopathological lesions mainly in adults at risk of CD. AIMS: The aim of this study was to evaluate the usefulness of human leukocyte antigen (HLA)-DQ2/8 genotyping, followed by duodenal biopsy for the detection of CD in adult first-degree relatives (FDRs) of patients with CD. MATERIALS AND METHODS: Ninety-two adult DQ2/8 positive FDRs were consecutively included. A duodenal biopsy was offered irrespective of the serology result or associated symptoms. The clinical features, associated autoimmune diseases and biochemical parameters were recorded. RESULTS: Sixty-seven FDRs (mean age 34 years) underwent a duodenal biopsy. Histopathological alterations were found in 32 (48%) and showed the following stages: 12 Marsh I (18%), one Marsh II (1.5%), four Marsh IIIA (6%), five Marsh IIIB (7.5%) and 10 Marsh IIIC (15%). Positive serological markers were present in 17/67 (25%), with only one showing Marsh I and the remainder presenting some degree of duodenal atrophy (Marsh III). In addition, 33/67 (54%) had gastrointestinal symptoms, with dyspepsia being the most prevalent. The distribution of symptoms, anaemia and autoimmune disease was independent of the duodenal histopathological stage. Serology-based screening would diagnose 50% of the cases showing any degree of CD spectrum and miss 6% of the cases with mucosal atrophy. CONCLUSION: Adult FDRs of patients with CD can benefit from a screening strategy on the basis of HLA-DQ genotyping, followed by a duodenal biopsy. Gastrointestinal symptoms and lymphocytic enteritis are common findings that may benefit from a gluten-free diet.