How can I differentiate between Celiac disease and non-Celiac gluten sensitivity in my patients?

Differentiating between coeliac disease (CD) and non-coeliac gluten sensitivity (NCGS) primarily relies on the definitive diagnostic pathway for coeliac disease, as the provided guidelines offer detailed criteria for CD and less specific diagnostic information for NCGS.

• Diagnosing Coeliac Disease (CD):
  • Serological Testing: Offer serological testing for CD to patients presenting with persistent unexplained abdominal or gastrointestinal symptoms, faltering growth, prolonged fatigue, unexpected weight loss, unexplained iron, vitamin B12 or folate deficiency, type 1 diabetes, autoimmune thyroid disease, irritable bowel syndrome (in adults), or if they are first-degree relatives of someone with CD ¹. Consider testing for metabolic bone disorder, unexplained neurological symptoms, unexplained subfertility or recurrent miscarriage, persistently raised liver enzymes, dental enamel defects, Down's syndrome, or Turner syndrome ¹.
  • Specific Serology: Laboratories should primarily test for total immunoglobulin A (IgA) and IgA tissue transglutaminase (tTG) ¹. If IgA tTG is weakly positive, IgA endomysial antibodies (EMA) should be used ¹. If IgA is deficient, IgG EMA, IgG deamidated gliadin peptide (DGP), or IgG tTG should be considered ¹.
  • Gluten Challenge: It is crucial to advise patients that any test for coeliac disease is accurate only if a gluten-containing diet is eaten during the diagnostic process ¹. Patients should eat some gluten in more than one meal every day for at least 6 weeks before testing ¹. Advise patients not to start a gluten-free diet until diagnosis is confirmed by a specialist, even if serological results are positive ¹. If a patient has restricted gluten intake and is reluctant to re-introduce it, refer them to a gastrointestinal specialist, explaining that confirming diagnosis by intestinal biopsy may be difficult ¹.
  • Endoscopic Intestinal Biopsy: Young people and adults with positive serological test results (unambiguously positive IgA tTG alone, or weakly positive IgA tTG and a positive IgA EMA test result, or any positive IgG antibody in IgA deficiency) should be referred to a gastrointestinal specialist for endoscopic intestinal biopsy to confirm or exclude coeliac disease ¹. Children with positive serological results should be referred to a paediatric gastroenterologist or paediatrician with a specialist interest in gastroenterology for further investigation, which may include an IgA EMA test, HLA genetic testing, or an endoscopic biopsy ¹.
  • HLA Testing: Human leukocyte antigen (HLA) DQ2/DQ8 testing should not be used for initial diagnosis in non-specialist settings ¹. It may be considered in specialist settings, such as for children not having a biopsy or individuals with limited gluten ingestion who choose not to have a gluten challenge ¹.
• Non-Coeliac Gluten Sensitivity (NCGS):
  • The provided context indicates that non-celiac gluten sensitivity is a recognized condition (Molina-Infante et al., 2014). However, the specific diagnostic criteria or tests for NCGS are not detailed within the provided UK guidelines or the content of the referenced literature. Therefore, the differentiation in clinical practice often involves ruling out coeliac disease and wheat allergy, with symptoms improving on a gluten-free diet, but without the specific serological markers or characteristic intestinal damage seen in coeliac disease.
• Key Differentiation: The definitive diagnosis of coeliac disease relies on a combination of specific serological markers and characteristic changes on intestinal biopsy while on a gluten-containing diet ¹. In contrast, non-coeliac gluten sensitivity is typically considered when coeliac disease has been thoroughly excluded using these established diagnostic methods, and symptoms persist with gluten ingestion but resolve on a gluten-free diet (Molina-Infante et al., 2014).