The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. The evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, possible therapeutic options, and monitoring for complications of this condition are included.
This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of great clinical importance for patients with celiac disease. Ten recommendations were extracted from the literature review and expert opinions. However, no systematic reviews were conducted on this topic; therefore, these recommendations do not carry formal qualifications with respect to the evidence or strength of the considerations presented.
List of recommendations:
Recommendations:
- In patients suspected of having celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of previous diagnostic tests, including serologies, endoscopies, and histological findings.
- In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (non-responsive celiac disease), continued gluten ingestion as a cause of these symptoms should be ruled out with serological testing, thorough dietary review, and detection of immunogenic peptides in feces or urine. And EGD with small bowel biopsies should be performed to look for villous atrophy. If villous atrophy persists, or the initial diagnosis of celiac disease was not confirmed, consider other causes of villous atrophy, including common variable immunodeficiency, autoimmune enteropathy, tropical disease, and drug-induced enteropathy.
- For patients with non-responsive celiac disease, after exclusion of gluten ingestion, perform systematic evaluation for other possible causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory disease intestinal, lactose or fructose intolerance and bacterial overgrowth in the small intestine.
- Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between refractory celiac disease subtypes and exclude enteropathy-associated T-cell lymphoma. Refractory celiac disease type 1 is characterized by a population of normal intraepithelial lymphocytes, and type 2 is defined by the presence of a population of aberrant clonal intraepithelial lymphocytes. Consultation with an expert hematopathologist is necessary to interpret these studies.
- Perform small bowel imaging with capsule endoscopy and computed tomography or magnetic resonance enterography to rule out T-cell lymphoma associated with enteropathy and ulcerative jejunoileitis in the initial diagnosis of refractory celiac disease type 2.
- Complete a detailed nutrition assessment with investigation of micronutrient and macronutrient deficiencies in patients diagnosed with refractory celiac disease. Albumin should be checked as an independent prognostic factor.
- Correct macro- and micronutrient deficiencies through oral supplements and/or enteral support. Consider parenteral nutrition for patients with severe malnutrition due to malabsorption.
- Corticosteroids, most commonly open capsule budesonide or, if not available, prednisone, are the medication of choice and should be used as first-line therapy in refractory type 1 or type 2 celiac disease.
- Patients with refractory celiac disease require regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to evaluate clinical and histological response to treatment. Identify local experts with experience in celiac disease to assist with management.
- Patients with refractory celiac disease unresponsive to steroids may benefit from referral to an experienced center for management or evaluation for inclusion in clinical trials.
