Mucosal Healing and Risk for Lymphoproliferative Malignancy in Celiac Disease

Abstract

Background Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the follow-up intestinal biopsy, performed to document mucosal healing. Objective To examine the association between mucosal healing in CD and later LPM. Design Population-based cohort study Setting We identified patients with CD from all of Sweden’s 28 pathology departments. Patients Individuals with CD who had a follow-up biopsy after initial diagnosis. Measurements We compared the risk of LPM to that of the general population using expected rates; and through Cox regression we compared the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95%CI 2.10–3.67), but this increase was greater among those with persistent villous atrophy (SIR 3.78; 95%CI 2.71–5.12) as compared to those with mucosal healing (SIR 1.50; 95%CI 0.77–2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95%CI 1.18–4.34). We found an increased risk of T cell lymphoma (HR 3.51; 95%CI 0.75–16.34), but no excess risk of B cell lymphoma (HR 0.97; 95%CI 0.21–4.49). Limitation We had no data on dietary compliance. Conclusions The increased LPM risk in CD is associated with the results of the follow-up biopsy, with a higher risk among those with persistent villous atrophy. Follow-up biopsy may be a means to effectively stratify CD patients regarding subsequent LPM risk. Primary funding source the National Center for Advancing Translational Sciences, National Institutes of Health, The American Scandinavian Foundation, the Celiac Sprue Association, Örebro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, the Swedish Research Council, and the Swedish Celiac Society.

Factors associated with long diagnostic delay in celiac disease

“…Further, untreated disease predisposes to complications such as osteoporotic fractures [10], infertility [11,12] and intestinal lymphoma [13,14]. An early initiated gluten-free diet reduces the incremental burden to health care and the risk of complications and also improves health-related quality of life [2,5,8,15].…”

Age-related differences in celiac disease: Specific characteristics of adult presentation

“…The lack of dietary compliance and persistence of histological damage, are two factors associated with the development of lymphoproliferative disease in adults, which is the most severe complication associated to CD [34] . A recent Swedish population study noted that celiac patients with persistent villous atrophy, during follow-up, had twice the risk of developing a malignant lymphoproliferative disease, mostly T lymphoma [35] . These findings make it necessary to recommend a control biopsy during the second year after diagnosis, in order to evaluate villous atrophy recovery.…”

The Role of an IgA/IgG-Deamidated Gliadin Peptide Point-of-Care Test in Predicting Persistent Villous Atrophy in Patients With Celiac Disease on a Gluten-Free Diet

“…Histological remission is not always achieved in adults, with remission rates ranging from 34%-65%. (9)(10)(11) This is an important point because persistent villous atrophy increases the risk of lymphoproliferative malignancies (HR 2.26) (12) and hip fractures (HR 1.67). (13) Consequently, the logical approach for disease monitoring would be histological assessment of the duodenum for mucosal healing.…”