Effect of Elemental Diet on Mucosal Immunopathology and Clinical Symptoms in Type 1 Refractory Celiac Disease

Background & Aims: Patients with celiac disease (CD) who do not improve or exhibit villous atrophy on a gluten-free diet may have type 1 refractory CD (RCD) with a polyclonal mucosal T-cell infiltrate, or type 2 RCD with a monoclonal infiltrate, also termed cryptic T-cell lymphoma. Both conditions are difficult to treat. Here we describe the effects of a nonimmunogenic elemental diet on clinical symptoms and mucosal immunopathology in type 1 RCD. Methods: Ten CD patients on a strict gluten-free diet were diagnosed with type 1 RCD after extensive clinical evaluation in a tertiary referral hospital. A 4-week amino-acid-based liquid elemental diet regimen was given with no other treatment, except in 1 patient who also received methotrexate. Duodenal biopsy specimens were obtained before and after treatment for histologic assessment, immunophenotyping of intraepithelial lymphocytes, T-cell receptor clonality, mucosal interleukin (IL)-15 expression, flow-cytometric analysis of interferon (IFN)-γ-secreting T cells, and whole biopsy specimen IFN-γ messenger RNA determination. Results: Nine patients completed the treatment; however, 1 patient did not tolerate the diet. Histologic improvement and reduced epithelial IL-15 were seen in 8 patients, whereas IFN-γ-secreting mucosal T cells and IFN-γ messenger RNA levels decreased in 4 and 7 patients, respectively. Clinical improvement was noted in 6 patients, with 1 patient showing normalization of hypoalbuminemia. Three patients could discontinue their total parenteral nutrition. Conclusions: Persistent mucosal IFN-γ and IL-15 production often occurs in type 1 RCD despite conventional treatment. Elemental diet is a therapeutic option that can provide long-term immunopathologic and clinical improvement of this difficult condition.