Histopathological Correlation in Suspected Celiac Disease: Linking Clinical, Serological, and Endoscopic Findings

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, characterized by villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Despite advances in serological testing, duodenal biopsy remains the diagnostic gold standard, especially in atypical or patchy disease. This retrospective study at King Fahd University Hospital (KFUH), Saudi Arabia, evaluated the diagnostic contribution of biopsies from the duodenal bulb (D1) and distal duodenum (D2) in 224 patients assessed for suspected CD between August 2023 and August 2024. Clinical, serological [IgA anti-tissue transglutaminase (anti-TG2), anti-endomysial antibodies (EMA), deamidated gliadin peptide], and histopathological data were analyzed. Sixty-five patients (29%) were diagnosed with CD. Villous atrophy, mucosal flattening, and increased intraepithelial lymphocytes were strongly associated with CD (p ≤ 0.001), and positive anti-TG2 and EMA correlated with Marsh grade. Combined D1 and D2 sampling improved diagnostic yield, underscoring the value of integrating histology and serology in evaluating classical and non-classical CD presentations.