Education practiceCeliac Disease and Persistent Symptoms
Section snippets
Clinical Scenario
A 52-year-old male is referred for persistent diarrhea, bloating, weight loss, and iron deficiency anemia following a diagnosis of celiac disease 1 year ago. At the time of his original diagnosis, serology was notable for a high IgA tissue transglutaminase titer >250 (normal less than 20), intraepithelial lymphocytosis and partial villous atrophy on small intestinal biopsy, and significant steatorrhea.
He reports being compliant with a gluten-free diet, though clinically his symptoms have only
The Problem
This vignette illustrates a case of nonresponsive celiac disease (NRCD). NRCD is defined by a lack of initial response to a prescribed gluten-free diet (GFD), or the recurrence of symptoms despite maintenance of GFD in a patient who responded initially to GFD. The exact prevalence of NRCD is unknown but the presence of symptoms after treatment with a GFD is common in patients with celiac disease (CD). This clinical problem requires a systematic diagnostic and therapeutic approach because of the
Does This Patient Have Celiac Disease?
The clinical case discussed here concerns a middle-aged man with a clinical diagnosis of CD well supported by typical symptoms (malabsorption), high titers of IgA tissue transglutaminase antibody (overall specificity >95%), and by the presence of partial villous atrophy in the duodenal biopsy. Thus, although the first step when faced with patients with NRCD is to evaluate the certainty of the original diagnosis, an alternative diagnosis in this case seems unlikely. When the original diagnosis
Areas of Uncertainty
The prevalence and causes of NRCD in the community are not known yet. The most cost-effective approach for NRCD remains to be determined. The long-term outcomes after intervention in patients with NRCD are incompletely understood. The best therapeutic approach for asymptomatic subjects with persistently abnormal mucosa after GFD is unknown.
Published Guidelines
The American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of CD published in 2006 outlines the key aspects of evaluating a celiac patient with persistent symptoms: verification of the original diagnosis and compliance with a GFD, and consideration of either other causes of NRCD or severe complications (eg, RCD and malignancies).
Recommendations for This Patient
In the patient described in the vignette, an empiric trial with pancreatic enzymes led to complete resolution of his symptoms. Gluten contamination was ruled out by an expert dietitian but adherence to GFD was reinforced. One year later, the patient remains asymptomatic 2 months after stopping pancreatic enzyme supplementation with both normal serology and histology.
References (0)
Cited by (20)
Celiac disease: What's new?
2023, Medecine des Maladies MetaboliquesCeliac Disease
2019, Mayo Clinic ProceedingsCitation Excerpt :If follow-up biopsy is considered, it should be done no sooner than 1 year after the gluten-free diet has been started and most ideally at 2 years to ensure the possibility for full healing before reassessment.90 Nonresponsive CD is a common clinical problem characterized by persistent or recurrent symptoms after starting a gluten-free diet.93 The most common symptoms are diarrhea, abdominal pain, weight loss, fatigue, and bloating.94
Diarrhoea due to small bowel diseases
2012, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :The treatment of coeliac disease is lifelong adherence to a gluten-free diet (elimination of wheat, barley and rye) [13]. When a patient with what seems to be a coeliac syndrome does not respond to a gluten-free diet, alternative or additional diagnoses need to be sought [14]. The most frequent cause of nonresponsive coeliac disease is inadvertent gluten contamination.
High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease
2012, Digestive and Liver DiseaseCitation Excerpt :In this context the right place for histology would be in assessing response to GFD [16] given the low sensitivity of t-TG in predicting mucosal healing and the risk of complications associated with persistent small intestinal atrophy [22]. As a final consideration we think that lack of the baseline histology is unlikely to affect diagnostic accuracy of refractory celiac disease in patients with persistent or aggravating symptoms during GFD, because criteria for this diagnosis are independent of the baseline histological characteristics [23]. The authors have no conflict of interest to declare.
Capsule endoscopy in nonresponsive celiac disease
2011, Gastrointestinal EndoscopyCitation Excerpt :CE may be indicated in treated patients who have alarm symptoms such as weight loss, fever, and severe abdominal pain. CE evaluation is not necessary when a cause for nonresponsive symptoms is evident such as intentional gluten contamination or microscopic colitis.51 Balloon-assisted enteroscopy may be helpful for sampling abnormal areas located beyond the reach of conventional endoscopy to exclude (or confirm) enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and/or adenocarcinoma in patients with complicated CD.52
This activity has an accompanying continuing medical education activity on page e8. Learning Objectives—At the end of this activity, the learner will know the diagnostic and management steps for individuals with celiac disease and persisting symptoms while on a gluten-free diet.
Conflicts of interest The authors disclose the following: Dr Murray has been a consultant to Astra Zeneca, Alvine, and Novartis, and an investigator for Alba Therapeutics and Dynagen. The remaining authors disclose no conflicts.
Funding This work was supported in part by NIH Training Grant in Digestive Diseases T32 DK07198 (to SHB), NIH Training Grant in Gastrointestinal Allergy and Immunology T32AI-07047 (to AR–T) and NIH Grant DK57892 (to JAM).