High Prevalence of Functional Gastrointestinal Disorders in Celiac Patients with Persistent Symptoms on a Gluten-Free Diet: A 20-Year Follow-Up Study

Abstract

Background: Ongoing symptoms in treated celiac disease (CD) are frequent and are commonly thought of as being due to infractions to a gluten-free diet (GFD) or complications.

Aims: To study the etiology and natural history of clinically relevant events (CREs) throughout follow-up and identify predictors thereof to guide follow-up.

Methods: CREs (symptoms/signs requiring diagnostic/therapeutic interventions) occurring in celiac patients between January-2000 and May-2021 were retrospectively collected between June and September 2021 and analysed.

Results: One-hundred-and-eighty-nine adult patients (133 F, age at diagnosis 36 ± 13 years, median follow-up 103 months, IQR 54-156) were enrolled. CREs were very common (88/189, 47%), but hardly due to poor GFD adherence (4%) or complications (2%). Interestingly, leading etiologies were functional gastrointestinal disorders (30%), reflux disease (18%) and micronutrient deficiencies (10%). Age at diagnosis ≥ 45 years (HR 1.68, 95%CI 1.05-2.69, p = 0.03) and classical pattern of CD (HR 1.63, 95%CI 1.04-2.54, p = 0.03) were predictors of CREs on a multivariable Cox model. At 5 years, 46% of classical patients ≥ 45 years old at diagnosis were event-free, while this was 62% for non-classical/silent ≥ 45 years, 60% for classical < 45 years, and 80% for non-classical/silent < 45 years.

Conclusions: CREs occurred in almost half of CD patients during follow-up, with functional disorders being very common. New follow-up strategies for adult CD may be developed based on age and clinical pattern at diagnosis.

Keywords: Celiac disease; Follow-up; Gluten-free diet; Persistent symptoms.

Fig. 1

Prevalence of patients with and without clinical events according to age group at diagnosis of celiac disease. *Cochran-Armitage trend test, p < 0.01

Fig. 2

Kaplan–Meier curve showing distribution of events over time from diagnosis of celiac disease

Fig. 3

Bar chart showing etiology of clinical events. GERD gastroesophageal reflux disease, GI gastrointestinal, GFD gluten-free diet CD coeliac disease, IBD inflammatory bowel disease, COPD chronic obstructive pulmonary disease. Functional GI disorders include: functional constipation, functional dyspepsia, irritable bowel syndrome, functional diarrhea. Two events which occurred in the context of poor GFD adherence (due to Helicobacter Pylori infection and dyslipidemia) were not included under poor GFD adherence as they were unrelated in nature to GFD adherence. Other etiologies included: colonic diverticular disease, colon polyps, dyslipidemia, dermatitis herpetiformis relapse, small intestinal bacterial overgrowth, COPD exacerbation, diabetic ketoacidosis in type 1 diabetes mellitus, acute gastroenteritis, ANCA-associated vasculitis, multifactorial anemia, hypercalcaemic syndrome, spondyloarthritis, osteoporosis, NSAID abuse, erosive gastritis, recurrent aphthous stomatitis

Fig. 4

Event-free follow-up rates according to age at diagnosis and clinical pattern of celiac disease at diagnosis (Oslo classification [25]). Group 1: Patients diagnosed at age ≥ 45 years with classical CD. Group 2: Patients diagnosed at age ≥ 45 years with non-classical/silent CD. Group 3: Patients diagnosed at age < 45 years with classical CD. Group 4: Patients diagnosed at age < 45 years with non-classical/silent CD