What are the next steps for a patient with abdominal pain after gluten intake, a negative celiac (celiac) test result, and an indication for a colonoscopy (c scope)?

Next Steps for Patient with Gluten-Related Pain and Negative Celiac Testing

Proceed with the colonoscopy as indicated, but first confirm the celiac disease diagnosis was properly excluded with upper endoscopy and duodenal biopsies while the patient was consuming gluten, then consider non-celiac gluten sensitivity as a diagnosis of exclusion. 1, 2

Confirm Proper Celiac Disease Exclusion

Before attributing symptoms to non-celiac gluten sensitivity, you must verify the diagnostic workup was complete:

• Confirm the patient was consuming adequate gluten (at least 10g daily for 6-8 weeks) when serologic testing was performed, as testing on a gluten-free or gluten-reduced diet yields false-negative results 1, 2

• Verify total IgA level was measured alongside IgA tissue transglutaminase (tTG-IgA), since IgA deficiency occurs in celiac disease and causes false-negative serology 1, 2

• Ensure upper endoscopy with duodenal biopsies was performed, not just serology alone—multiple biopsies (ideally 6 total: 1-2 from duodenal bulb and at least 4 from second part of duodenum) are required to confirm or exclude celiac disease 3, 1

• If biopsies were not obtained, the diagnosis of celiac disease has not been properly excluded, and upper endoscopy should be performed before labeling this as non-celiac gluten sensitivity 3

Consider HLA Testing in Select Cases

If the diagnostic workup was equivocal or the patient started a gluten-free diet before testing:

• HLA-DQ2 and HLA-DQ8 testing has >99% negative predictive value—absence of both alleles essentially rules out celiac disease 3, 1, 2

• This is particularly useful when celiac disease is strongly suspected despite negative serology, in patients with equivocal biopsy findings, or in patients already on a gluten-free diet who were never properly tested 1, 2

Proceed with Colonoscopy as Indicated

The colonoscopy should not be delayed by the gluten-related symptoms:

• Complete the colonoscopy for whatever indication prompted it (age-appropriate screening, alarm symptoms, evaluation of other pathology) 3

• The colonoscopy may identify alternative diagnoses that explain the abdominal pain, such as microscopic colitis, inflammatory bowel disease, or other colonic pathology 3, 4

Evaluate for Non-Celiac Gluten Sensitivity

Once celiac disease and wheat allergy are excluded and the colonoscopy is completed:

• Non-celiac gluten sensitivity (NCGS) is a diagnosis of exclusion characterized by intestinal and extraintestinal symptoms (abdominal pain, bloating, bowel habit abnormalities, fatigue, "foggy mind") that occur soon after gluten ingestion and resolve with gluten withdrawal 5, 6

• The diagnosis requires a clear cause-effect relationship established by double-blind, placebo-controlled gluten challenge, though this is cumbersome in clinical practice 7, 5

• In real-world practice, a therapeutic trial of strict gluten-free diet for 6 weeks followed by gluten rechallenge can establish the diagnosis if symptoms clearly resolve and recur 5, 6

• NCGS may be transient, so gluten tolerance should be reassessed over time 5

Evaluate for Other Causes of Symptoms

If symptoms persist despite gluten avoidance or if the gluten relationship is unclear:

• Consider irritable bowel syndrome, which can coexist with or mimic gluten sensitivity 3, 4

• Evaluate for small intestinal bacterial overgrowth (SIBO), which causes similar bloating and pain 3, 4

• Test for lactose or fructose intolerance, which commonly cause abdominal pain and bloating 3, 4

• Consider pancreatic exocrine insufficiency if steatorrhea or weight loss is present 3, 4

• Evaluate for microscopic colitis if diarrhea is prominent, which may be identified on colonoscopy biopsies 3, 4

Common Pitfalls to Avoid

• Do not diagnose NCGS without first properly excluding celiac disease with both serology and duodenal biopsies performed while consuming gluten 1, 2, 5

• Do not rely on symptom improvement with gluten avoidance alone as proof of gluten sensitivity—this has very low positive predictive value and many conditions improve with dietary modification 3, 5

• Do not assume negative serology excludes celiac disease—seronegative celiac disease occurs, and biopsy remains the gold standard 3, 1

• Do not delay indicated colonoscopy to pursue gluten-related workup, as the colonoscopy may reveal the true cause of symptoms 3