Clinical Staging and Survival in Refractory Celiac Disease: A Single Center Experience

Background & Aims

Refractory celiac disease (RCD) occurs when both symptoms and intestinal damage persist or recur despite strict adherence to a gluten-free diet. In RCD, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The aim is to describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD.

Methods

We compared the clinical characteristics and outcome in 57 patients with RCD: 42 with RCD I and 15 with RCD II.

Results

Fifteen of 57 patients died during follow-up (n = 8 with RCD I and n = 7 with RCD II), each within the first 2 years after RCD diagnosis. The overall 5-year cumulative survival is 70%, 80%, and 45% for the entire cohort, RCD I, and RCD II, respectively. The refractory state itself and enteropathy-associated T-cell lymphoma (EATL) were the most common causes of death, respectively. A new staging system is proposed based on the cumulative effect of 5 prognostic factors investigated at the time of the refractory state diagnosis: for patients in stages I, II, and III, the 5-year cumulative survival rate was 96%, 71%, and 19%, respectively (P < .0001).

Conclusions

RCD is associated with high mortality with RCD II having an especially poor prognosis because of the development of EATL. A new staging model is proposed that may improve the precision of prognosis in patients with RCD.

Abbreviations used in this paper: 2-CDA, 2-chlorodeoxyadenosine, ASCT, autologous hematopoietic stem-cell transplantation, CD, celiac disease, CI, confidence interval, CT, computerized tomography, EATL, enteropathy-associated T-cell lymphoma, EMA, endomysial antibodies, GFD, gluten-free diet, HLA, human leukocyte antigen, RCD, refractory celiac disease, tTGA, tissue transglutaminase antibodies