Special ArticleMonitoring Non-responsive Patients with Celiac Disease
Section snippets
Celiac disease
Celiac disease (Cd) is an inflammatory small intestinal disorder that is triggered by the ingestion of gluten proteins from wheat, barley and rye [1], [2], [3], [4], [5], [6], [7]. Its prevalence in the USA, most Western and middle Eastern countries ranges from 1:80–1:200 [3], [4], [5], [7], [8], [9], [10], [11]. Patients with Cd show a characteristic small intestinal (duodenal) histology of intraepithelial and subepithelial lymphocytic infiltration, villous atrophy and crypt hyperplasia. While
Diagnosis of celiac disease
The sensitivity of conventional video endoscopy to detect celiac disease is low. In a prospective study endoscopic markers for celiac disease, ie, loss and scalloping of duodenal folds, fissuring and mosaic pattern of the duodenal mucosa, had a sensitivity of only 50% and a specificity of 99.6%, with positive and negative predictive values of 60% and 99.4%, respectively [26]. Therefore, at least 3 biopsy specimens taken by “jumbo” forceps should be obtained from the distal duodenum of patients
Refractory celiac disease and intestinal lymphoma
Refractory celiac disease (RCd) can develop in 5–10% of adults with long-standing (often undetected) Cd. Patients do not respond to or relapse while on a strictly gluten-free diet. 158 Cd patients underwent follow-up small intestine biopsies within 2 years after starting a gluten-free diet [34]. Of 11 patients (7.0%) with persisting symptoms and villous atrophy who were considered to have RCd, five developed intestinal lymphoma.
The diagnosis of RCd can only be made when (inadvertent) gluten
Role of video endoscopy in celiac disease patients with persisting symptoms despite being on a gluten-free diet
There is a continuing debate on the benefits of video capsule endoscopy (VCE) over endoscopy and biopsy in patients with suspected or known (uncomplicated) Cd. Petroniene and colleagues [50] compared VCE to endoscopy in 10 patients with histologically proven villous atrophy and 10 non-celiac controls. Four blinded investigators assessed the VCE images, with an overall sensitivity of 70% and a specificity of 100% and a perfect interobserver agreement (kappa = 1.0). Two studies in patients with
Summary
Current data clearly suggest that VCE has an important role in the diagnostic workup of complicated Cd, especially in those cases with suspected RCd or EATL. This is supported by the high yield of relavant pathological findings in distal parts of the small intestine, such as severe ulceration and mucosal infiltration, by VCE compared to conventional upper GI endoscopy. In this setting, VCE allows for an assessment of the extent of small bowel involvement, detection of overt though often small
Acknowledgment
Part of the cited research of DS has been supported by research grants from the German Research Council (DFG) and the NIH, grant 1 R21 DK073254-01.
References (60)
Current concepts of celiac disease pathogenesis
Gastroenterology
(2000)- et al.
AGA technical review on Celiac Sprue. American Gastroenterological Association
Gastroenterology
(2001) - et al.
Coeliac disease
Lancet
(2003) - et al.
Coeliac disease in the year 2000: exploring the iceberg
Lancet
(1994) - et al.
Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum
Gastroenterology
(2001) - et al.
Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease
Gastroenterology
(1999) - et al.
Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues
Gastroenterology
(2002) - et al.
Gliadin T cell epitope selection by tissue transglutaminase in celiac disease
J Biol Chem
(2002) - et al.
Characterization of cereal toxicity for celiac disease patients based on protein homology in grains
Gastroenterology
(2003) Reevaluation of duodenal endoscopic markers in the diagnosis of celiac disease
Gastrointest Endosc
(2000)
Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’)
Gastroenterology
Antibody and genetic testing in coeliac disease
Pathology
Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice
Am J Gastroenterol
Etiology of nonresponsive celiac disease: results of a systematic approach
Am J Gastroenterol
High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal
Am J Gastroenterol
Abnormal intestinal intraepithelial lymphocytes in refractory sprue
Gastroenterology
Refractory celiac disease
Gastroenterology
Refractory coeliac disease
Best Practice and Research Clinical Gastroenterology
Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease
Gastroenterology
A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease
Immunity
Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease
Immunity
Association of celiac disease and intestinal lymphomas and other cancers
Gastroenterology
Capsule endoscopy in celiac disease: Diagnosis and management. Gastrointest Endoscopy
Clin N Am
The value of wireless capsule endoscopy in patients with complicated celiac disease
Gastrointest Endosc
DBE-European Study Group. The European experience with double-balloon enteroscopy: indications, methodology, safety, and clinical impact
Gastrointest Endosc
Celiac sprue
N Engl J Med
Celiac sprue
N Engl J Med
Celiac Disease
Curr Treat Options Gastroenterol
Pathomechanisms in celiac disease
Int Arch Allergy Immunol
Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study
Arch Intern Med
Cited by (14)
Small bowel endoscopy and coeliac disease
2012, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :Non-responsive coeliac disease is however defined by a lack of initial response to a prescribed gluten free diet, or the recurrence of symptoms despite maintenance of a gluten free diet in a patient who initially responded [52]. The most common cause of non-responsive coeliac disease is either inadvertent or deliberate gluten exposure, which has been reported to occur in up to 50% of treated adult coeliac disease patients [53,54]. Although the presence of persisting circulating EMA or tTG antibodies strongly correlates with dietary mistakes [55], over 80% of patients with persisting Marsh 3 lesion whilst on gluten free diet do not have elevated levels of tTG IgA [52,56].
Enteroscopy in the Diagnosis and Management of Celiac Disease
2009, Gastrointestinal Endoscopy Clinics of North AmericaCitation Excerpt :A minimal, but continuous, intake of gluten can prevent mucosal recovery.68 However, when the dietary compliance is established by a dietician, and the patient still does not respond, the initial diagnosis of celiac disease must be reassessed, and other reasons for persisting symptoms (ie, pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, inflammatory bowel disease, microscopic colitis, tropical sprue) must be ruled out.69 When clinical symptoms and histologic abnormalities persist or recur despite a strict adherence to the diet for more than 12 months, patients are defined as suffering from RCD.16,70–72
Refractory Coeliac Disease: An Opportunity to Prevent a T-Cell Lymphoma
2009, Science of Gluten-Free Foods and BeveragesCeliac disease: Management of persistent symptoms in patients on a gluten-free diet
2012, World Journal of GastroenterologyGluten-free diet - Update 2017
2017, Zeitschrift fur GastroenterologieModern diagnosis of celiac disease and relevant differential diagnoses in the case of cereal intolerance
2014, Allergo Journal International