Global Prevalence and Clinical Manifestations of Celiac Disease Among First-Degree Relatives: A Systematic Review and Meta-Analysis

INTRODUCTION: First-degree relatives (FDRs) of patients with celiac disease (CeD) are at high risk for developing CeD. We conducted a systematic review and meta-analysis to estimate CeD prevalence and clinical manifestations by analyzing studies that used the anti-tissue transglutaminase antibody test for screening. METHODS: In this systematic review with meta-analysis, studies published in PubMed, Web of Science, Embase, and Scopus were searched up to January 11, 2024, using keywords related to CeD and FDRs. Random-effects models were used, with heterogeneity assessed using the Cochran Q test and the I 2 statistic performed in STATA 18. RESULTS: Of 8,764 studies screened, 34 studies involving 10,016 FDRs of patients with CeD were included. The pooled estimates for seroprevalence and the biopsy-confirmed CeD prevalence in FDRs were 11% (95% CI: 9%–13%) and 7% (95% CI: 6%–9%), respectively. Daughters and sisters had the highest prevalence rates at 23% and 14%, compared with sons and brothers at 6% and 9%, respectively. Regional analysis revealed the highest seroprevalence estimates in Hungary (24%) and Cuba (19%), while the highest prevalence of biopsy-confirmed CeD was reported in Serbia (16%) and the United States (15%). Abdominal pain (42%), bloating (39%), and flatulence (38%) were the most common gastrointestinal symptoms, while 34% of FDRs with CeD were asymptomatic. In addition, pallor was the most frequent nongastrointestinal symptom (54%). DISCUSSION: Approximately 1 in 14 FDRs of patients with CeD is estimated to have CeD, with 1 in 4 daughters, 1 in 7 sisters, 1 in 11 brothers, 1 in 16 sons, and 1 in 20 fathers and mothers could be affected. Routine screening for FDRs could support early detection and management of CeD.