What is the appropriate next treatment for a 20‑year‑old male on a gluten‑free diet with persistent abdominal discomfort and excessive flatulence?

Confirm Celiac Disease Diagnosis Before Proceeding

This patient requires immediate diagnostic testing to confirm or exclude celiac disease before any treatment decisions, as he appears to have started a gluten-free diet without proper diagnostic evaluation. 1

Critical First Step: Establish the Diagnosis

The most pressing issue is that this patient is already on a gluten-free diet with persistent symptoms, which creates a diagnostic dilemma. You must determine whether celiac disease was ever properly diagnosed with both serology and biopsy while consuming gluten. 1

If No Prior Diagnostic Testing Was Done:

• Perform tissue transglutaminase IgA (TG2-IgA) and total IgA level immediately, even though he's on a gluten-free diet 1
• If serology is positive despite the gluten-free diet, this strongly suggests celiac disease and warrants upper endoscopy with duodenal biopsies 1
• If serology is negative and HLA-DQ2/DQ8 testing is positive, institute a formal gluten challenge: have the patient consume three slices of wheat bread daily for 1-3 months, then repeat TG2-IgA and proceed to biopsy if positive 1
• HLA-DQ2/DQ8 testing has value primarily for its negative predictive value—if negative, celiac disease is essentially ruled out 1, 2

Common Pitfall to Avoid:

Never assume celiac disease based on symptom response to a gluten-free diet alone. 1 Many conditions improve with gluten restriction, including non-celiac gluten sensitivity (NCGS), irritable bowel syndrome (IBS), and even placebo effects. 1 Without confirmed diagnosis, you cannot provide appropriate long-term management or assess for complications like osteoporosis, nutritional deficiencies, or lymphoma risk. 2

If Celiac Disease Is Confirmed:

Evaluate for Inadequate Gluten Restriction:

• Refer to a registered dietitian experienced in celiac disease to assess for hidden gluten sources 2, 3
• Review all medications and supplements with a pharmacist, as these frequently contain gluten in inactive ingredients 3
• Ask specifically about communion wafers and other non-food exposures 3
• Some patients demonstrate "exaggerated sensitivity" requiring stricter avoidance than standard recommendations 3

Address Persistent Symptoms Despite Strict Gluten-Free Diet:

If the patient is truly adherent to a gluten-free diet but symptoms persist, consider these alternative diagnoses systematically:

• Small intestinal bacterial overgrowth (SIBO): Consider hydrogen breath testing with glucose or lactulose, particularly if the patient has risk factors like chronic diarrhea or dysmotility 1
• Lactose intolerance: Common in celiac disease due to brush border damage; may persist even after mucosal healing 1, 3
• Fructose intolerance or fructan sensitivity: In some patients with self-reported NCGS, fructans in gluten-rich foods rather than gluten cause symptoms 1
• Microscopic colitis or pancreatic insufficiency: Should be considered with persistent diarrhea 3
• IBS overlap: Can coexist with celiac disease 1

Specific Management for Flatulence and Bloating:

• Trial of partially hydrolyzed guar gum (PHGG) 11g daily: This soluble fiber accelerates colonic transit and improves bowel frequency with lower bloating risk than psyllium due to reduced viscosity 4
• Avoid insoluble fibers like wheat bran entirely, as these consistently worsen bloating 4
• If PHGG fails after 4-6 weeks, escalate to polyethylene glycol (PEG) for constipation-predominant symptoms 4
• Consider a low-FODMAP diet trial if fructan sensitivity is suspected 1

If Celiac Disease Is Excluded:

Consider Non-Celiac Gluten Sensitivity (NCGS):

• NCGS is an immune-mediated reaction to gluten or fructan components 1
• Diagnosis of NCGS should only be considered after celiac disease has been ruled out with appropriate testing (celiac serology, small bowel histology in patients not following a gluten-free diet, and HLA-DQ typing) 1
• In confirmed NCGS, dietary restriction of gluten-containing foods is the cornerstone of treatment 1
• Trial elimination of fructans only may be sufficient, as fructans rather than gluten cause symptoms in some patients 1

Evaluate for IBS:

If celiac disease and NCGS are excluded, this presentation is consistent with IBS:

• Confirm the relationship between abdominal pain and altered bowel habit 1
• Bloating with visible distension is highly suggestive of IBS 1
• Baseline investigations should include CBC, CRP or ESR, and celiac serology (already done) 1
• Consider faecal calprotectin if diarrhea-predominant and age <45 years 1

Critical Monitoring If Celiac Disease Is Confirmed:

• Repeat TG2-IgA at 6 months, 12 months, then yearly 1
• Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure 1
• Negative serology does not guarantee mucosal healing—if symptoms persist or relapse without obvious explanation, perform upper endoscopy with biopsies 1
• Test for micronutrient deficiencies (iron, folate, vitamin D, B12) at diagnosis 1, 2
• Screen for osteoporosis, as fracture risk increases 60-100% before diagnosis but normalizes after one year on a gluten-free diet 2

The bottom line: Do not proceed with empiric treatment until you establish whether this patient has celiac disease, NCGS, IBS, or another condition entirely. Proper diagnosis fundamentally changes management, monitoring, and prognosis. 1