Celiac disease

Numbers (% or LR)
Prevalence0.7% [1,2]
Risk Factor
1. Type 1 DM LR 9 [1-3]
2. 1st Degree relative LR 9 [1-3]
3. Type 1 DM and 1st degree relativeLR 12 [1-3]
Symptoms/Syndrome
1. Malabsorption LR 5
2. Short stature/Failure to thriveLR 3
3. Unexplained anemiaLR 1.5 [4]
4. Neuropathy LR 1.5 [5]
5. Arthralgias LR 1.5
6. Unexplained transaminitis LR 1.5
7. No clinical symptoms or syndrome LR 0.8
TestClinical sensitivityClinical specificity
1. Anti-gliadin antibody (AGA)98% [1,2] 98% [1,2]
Other
Explanation for + test without disease:
Hypergammaglobulinemia, autoimmune diseases, chronic liver disease, congestive heart failure and enteric infections.[1]
Explanation for - test with disease:
Early stages of CD development, patients who have adopted a reduced-gluten diet before testing.
Impaired immunoregulation, use of immunosuppressants.[1]
Example of high value use:
Patient with symptoms or signs consistent with celiac disease or at high risk of celiac disease (e.g., positive family history, type 1 diabetes, Hashimoto thyroiditis, Down syndrome).[2]
Example of low value use:
Screening patients without specific risk factors. [2]
Choosing wisely or other guidance:
CW: “Avoid ordering screening tests looking for chronic illness or an endocrine cause, including CBC, CMP, IGF-1, thyroid tests, and celiac antibodies, in healthy children who are growing at or above the 3rd percentile for height with a normal growth rate (i.e., not crossing percentiles) and with appropriate weight gain.
Even in children who are below the 3rd percentile for height with a normal history and physical exam, the incidence of newly diagnosed pathology was found to be only about 1%. In patients who have significant short stature (e.g. ≤-2.5 SD) or who are well below their genetic potential based on parental heights, tiered or sequential screening may be considered.”[6]

Discussion

Prevalence and risk factors:

Celiac disease is estimated to affect approximately 1% of the population, although that may vary by region of the world. Most patients with celiac disease are not diagnosed. Chance of celiac disease increases significantly in patients with a close relative or if they have type 1 diabetes. The estimates of increase in risk are ~3-10% for either of these risk factors which would indicate a LR of ~9.[1–3]
If both factors present, it was estimated to increase LR to 12 as they are not fully independent.

Symptoms/Syndromes:

Likelihood ratios for symptoms or syndromes was very limited. In a recent review, frequency of celiac disease was listed for certain syndromes but these numbers likely reflect highly varied populations as arthritis appears equally predictive as GI symptoms.[2]
As with other diseases where likelihood ratios were not well defined, we categorized sign/symptom impact into low (LR 1.5), medium (LR 3.0) and high (LR 5.0).

Test sensitivity & specificity:

The anti-TTG IgA was reported by various reviews as having a range of sensitivity and specificity that varied from a sensitivity of 78%-99% and specificity of 90-99%.[1,2] Those reviews identified most likely estimates of current tests at 98% sensitivity and 98% specificity.

References

  1.  Al-Toma A, Volta U, Auricchio R, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterology Journal. 2019;7(5):583-613. doi:10.1177/2050640619844125

  2. Leonard MM, Sapone A, Catassi C, Fasano A. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA. 2017;318(7):647-656. doi:10.1001/jama.2017.9730

  3. Shah S, Smyth J, Simpson V. G226(P) Coeliac disease surveillance in children and young persons with type 1 diabetes-are we compliant? Archives of Disease in Childhood. 2018;103(Suppl 1):A93-A94. doi:10.1136/archdischild-2018-rcpch.221

  4. Mahadev S, Laszkowska M, Sundström J, et al. Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis. Gastroenterology. 2018;155(2):374-382.e1. doi:10.1053/j.gastro.2018.04.016

  5. Therrien A, Kelly CP, Silvester JA. Celiac Disease: Extraintestinal Manifestations and Associated Conditions. J Clin Gastroenterol. 2020;54(1):8-21. doi:10.1097/MCG.0000000000001267

  6. Screening tests for chronic illness or endocrine cause | Choosing Wisely. Published September 25, 2017. Accessed July 13, 2021. https://www.choosingwisely.org/clinician-lists/aap-soen-screening-tests-for-chronic-illness-or-endocrine-cause/

 Authors: Eric Schultz, Deborah Korenstein, Daniel Morgan