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  • Title: AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review.
    Author: Green PHR, Paski S, Ko CW, Rubio-Tapia A.
    Journal: Gastroenterology; 2022 Nov; 163(5):1461-1469. PubMed ID: 36137844.
    Abstract:
    DESCRIPTION: The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition. METHODS: 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 high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: In patients believed to have celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. BEST PRACTICE ADVICE 2: In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (nonresponsive celiac disease), ongoing gluten ingestion should be excluded as a cause of these symptoms with serologic testing, dietitian review, and detection of immunogenic peptides in stool or urine. Esophagogastroduodenoscopy 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 sprue, and medication-induced enteropathy. BEST PRACTICE ADVICE 3: For patients with nonresponsive celiac disease, after exclusion of gluten ingestion, perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, lactose or fructose intolerance, and small intestinal bacterial overgrowth. BEST PRACTICE ADVICE 4: Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between subtypes of refractory celiac disease and to exclude enteropathy-associated T-cell lymphoma. Type 1 refractory celiac disease is characterized by a normal intraepithelial lymphocyte population and type 2 is defined by the presence of an aberrant, clonal intraepithelial lymphocyte population. Consultation with an expert hematopathologist is necessary to interpret these studies. BEST PRACTICE ADVICE 5: Perform small bowel imaging with capsule endoscopy and computed tomography or magnetic resonance enterography to exclude enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis at initial diagnosis of type 2 refractory celiac disease. BEST PRACTICE ADVICE 6: Complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies in patients diagnosed with refractory celiac disease. Check albumin as an independent prognostic factor. BEST PRACTICE ADVICE 7: Correct deficiencies in macro- and micronutrients using oral supplements and/or enteral support. Consider parenteral nutrition for patients with severe malnutrition due to malabsorption. BEST PRACTICE ADVICE 8: Corticosteroids, most commonly open-capsule budesonide or, if unavailable, prednisone, are the medication of choice and should be used as first-line therapy in either type 1 or type 2 refractory celiac disease. BEST PRACTICE ADVICE 9: Patients with refractory celiac disease require regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy. Identify local experts with expertise in celiac disease to assist with management. BEST PRACTICE ADVICE 10: Patients with refractory celiac disease without response to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials.
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