Background
Despite adherence to a gluten-free diet (GFD), a significant proportion of celiac disease (CeD) patients remain non-responsive (NRCD). We systematically evaluated NRCD patients on GFD for ≥12 months to determine causes of non-responsiveness.
Methods
In this prospective study, 299 CeD patients were classified as GFD-responsive or non-responsive based on symptoms, IgA anti-tTG levels, and histology. Investigations included serum IgA anti-tTG titre, HLA haplotyping, immunophenotyping of intraepithelial lymphocytes (IELs) by IHC and flow cytometry, TCR gamma clonality assay, and evaluation for other gastrointestinal (GI) disorders.
Results: Of 299 patients, 170 (56.9%) were NRCD. Among them, 20% (34/170) had other associated disorders, namely inflammatory bowel disease (2.9%), irritable bowel syndrome (2.9%), chronic hepatitis (1.8%), intestinal tuberculosis (1.2%), and lactose intolerance (1.2%), along with few others, each with normal serology and histology on follow up. A majority of NRCD patients (65.3%, 111/170) were GFD non-compliant with elevated serology and/or abnormal histology. A subset of patients (12.9%, 22/170) with enteropathy changes on follow up and normal serology were identified as either slow responders (4.7%) or having other associated GI disorders. After excluding other causes, 3 (1.8%) were diagnosed as refractory CeD (type 1), with no aberrant IEL immunophenotype.
Conclusions: Gluten non-compliance is the leading cause of GFD non-responsiveness. NRCD patients need thorough evaluation for other GI disorders despite being a diagnosed case of CeD on therapy. Prevalence of RCD-type 1 in this region is low (1.76%).