Presentation and Long-Term Follow-up of Refractory Celiac Disease: Comparison of Type I With Type II

Background & Aims

Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival.

Methods

Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses.

Results

At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P < .05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P < .01), clonality (P = .01), and overt lymphoma (P = .001) predicted short survival time. Only abnormal IEL phenotype (P = .03) and overt lymphoma (P = .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II.

Conclusions

RCD II has a much more severe presentation and prognosis than patients with RCD I; <44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.

Abbreviations used in this paper: CT, computed tomography, EC, epithelial cell, GFD, gluten-free diet, IEL, intraepithelial lymphocyte, RCD, refractory celiac disease, TCR, T-cell receptor