Consensus and Guidelines · March 11, 2014
TAKE-HOME MESSAGE
- Using a retrospective review of 238 patient records, the authors developed a diagnostic algorithm for the differential diagnosis of celiac disease (CD) and non-celiac gluten sensitivity (NCGS).
- In determining a diagnostic algorithm to differentiate CD from NCGS, the authors concluded that individuals with negative celiac serology who are on a regular diet are unlikely to have celiac disease, whereas those with negative serology who lack clinical evidence of malabsorption and CD risk factors are likely to have NCGS.
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Is It Celiac Disease or Non-Celiac Gluten Sensitivity?
This study helps us accurately diagnose a patient with celiac disease (CD) vs non-celiac gluten sensitivity (NCGS). Since CD has long-term health consequences (gastrointestinal malignancy, osteoporosis, etc.), it is important to adequately diagnose this condition as many people with NCGS are inaccurately diagnosed with CD. CD also requires strict gluten restriction while those with NCGS often do fine with keeping gluten load to a minimum with the ability to titrate based on the severity of their symptoms. All subjects in this study were referred to a tertiary-care center and had improvement in symptoms with a gluten free diet (GFD). The report by Kabbani and colleagues suggests the following protocol for differential diagnosis, which is illustrated in a useful figure found in the paper. I have attempted to simplify this figure with a summary table below.
Question 1: Is the CD serology test positive? Check tTG-IgA (transglutaminase IgA) and DGP (deamidated gliadin peptide) antibodies; if positive, CD is likely.
Question 2: Are there signs and symptoms of malabsorption? These include weight loss, diarrhea, and abnormal nutrient testing with low vitamin D, iron, B12, and/or zinc. (Low vitamin D and iron were most predictive for CD in this study). Note that chronic acid suppression medications can also cause malabsorption.
Question 3: Is there a family history of CD or a personal history of autoimmune disease?
- If the answers to all of these queries are negative and the patient feels better on a gluten-free diet, the diagnosis is NCGS, and endoscopy with biopsy is not needed.
- If serology is negative, but answers to questions 2 and/or 3 are positive, order HLA genetic testing. If negative, the patient has NCGS. If positive, order endoscopy with biopsy.
- It is important to keep in mind that serology testing must be done while the patient is eating gluten or the risk of a false-negative test is high. Although the timing is variable, gluten should be eaten for 8 weeks to stimulate antibodies. If the patient cannot tolerate gluten, genetic HLA-DQ2/DQ8 testing should be considered. If negative, the patient has NCGS.
Characteristic CD NCGS Bowel pattern More diarrhea More constipation Age Presents later Presents earlier Serology (tTG-IgA, DGP) Positive Negative Symptoms of malabsorption (weight loss, diarrhea) More common Less common Genetic testing: HLA-DQ2/DQ8. Note that this test is positive in 40%; a negative test is most useful to rule out CD. Order if serology is borderline with symptoms of malabsorption. Negative=NCGS
Not needed if serology is negative Family history Positive Negative Other autoimmune disease Positive Negative Endoscopy and biopsy To confirm CD Rarely necessary
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.
Am. J. Gastroenterol 2014 Mar 11;[EPub Ahead of Print], TA Kabbani, RR Vanga, DA Leffler, J Villafuerte-Galvez, K Pallav, J Hansen, R Mukherjee, M Dennis, Ciaran Kelly