Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis.

The American journal of gastroenterology. 2014;109(5):741-6; quiz 747

Plain language summary

Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is challenging, as both conditions respond to a gluten-free diet but present different clinically. At present, an effective diagnostic protocol specific to NCGS is not available. The aim of this review is to develop a diagnostic algorithm to differentiate CD from NCGS. Records of 238 subjects who presented with gluten-responsive symptoms were reviewed. This study resulted in a clinical model for efficient differential diagnosis of CD and NCGS. On the basis of this model, unnecessary endoscopies could have been avoided in over 60% of subjects. This model offers clinicians a stepwise algorithm for diagnosis and management of patients who present with symptoms responsive to gluten exclusion.

Abstract

OBJECTIVES Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. METHODS We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. RESULTS Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (P<0.0001). In addition, CD subjects were significantly more likely to have a family history of CD (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001). The positive likelihood ratio for diagnosis of CD of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. CONCLUSIONS On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.

Lifestyle medicine

Patient Centred Factors : Triggers/Gluten
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition

Methodological quality

Allocation concealment : Not applicable
Publication Type : Evaluation Study ; Journal Article

Metadata