Celiac Disease: Symptoms and Management
Clinical Presentation
Celiac disease presents with a highly variable clinical spectrum ranging from classic malabsorptive symptoms to subtle extraintestinal manifestations, and many patients may be entirely asymptomatic. 1, 2
Classic Gastrointestinal Symptoms
- Chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating are the hallmark malabsorptive symptoms that should prompt immediate testing for celiac disease 1
- Diarrhea is the most frequent symptom in untreated celiac disease, though steatorrhea occurs in only one-fifth of patients 3
- Alternating diarrhea and constipation is common and both respond to gluten-free diet 3
- Abdominal pain and bloating affect most patients and typically resolve with dietary treatment 3
Non-Classic Presentations (Increasingly Common)
Most adult patients now present with non-classic symptoms rather than the traditional malabsorptive picture 1, 4:
- Unexplained iron deficiency anemia (substantial prevalence warranting testing) 1, 4
- Abnormal liver function tests/transaminitis 2, 4
- Osteomalacia and osteoporosis 1, 4
- Neurological manifestations including neuropathy, ataxia, and depression 1
- Dermatitis herpetiformis 1
- Recurrent miscarriage and adverse pregnancy outcomes 1, 4
- Short stature and failure to thrive in children 1
Asymptomatic Disease
- Many individuals with celiac disease have no symptoms at all and are diagnosed through screening of high-risk populations 1, 2
- Asymptomatic patients are typically identified through screening of first-degree relatives or those with associated autoimmune conditions 1
High-Risk Populations Requiring Testing
Testing should be performed in patients with symptoms of malabsorption AND in asymptomatic individuals with specific risk factors 1:
- First-degree relatives of patients with celiac disease (10% prevalence) 1
- Type 1 diabetes mellitus 1, 4
- Autoimmune thyroid disease 1, 4
- Autoimmune liver disease 1
- Down syndrome and Turner syndrome 1, 4
- Irritable bowel syndrome symptoms 1
Diagnostic Approach
Serological Testing (Must Be Done BEFORE Gluten-Free Diet)
IgA anti-tissue transglutaminase (TTG) antibody is the preferred initial test for all persons older than two years 1, 4:
- All diagnostic serologic testing must be performed before initiating a gluten-free diet, as gluten avoidance reduces sensitivity of both serology and biopsy 1
- Total IgA should be measured simultaneously in high-risk patients (first-degree relatives) to exclude IgA deficiency 1
- If IgA deficiency is present, perform IgG-based testing (IgG-TTG or IgG-deamidated gliadin peptides) 1
- Antibodies against native gliadin are no longer recommended for primary detection 1
Confirmatory Biopsy
Upper endoscopy with multiple duodenal biopsies remains the diagnostic gold standard and is required in most patients 1, 2:
- Obtain one to two biopsies from the duodenal bulb and at least four from the distal duodenum to maximize diagnostic yield 1
- Biopsy is required even with positive serology to confirm diagnosis before lifelong dietary restriction 1
- If biopsies are performed first and show celiac changes, celiac-specific serology should still be obtained as confirmatory testing 1
Critical pitfall: Lymphocytic infiltration without villous atrophy is not specific for celiac disease; consider alternative diagnoses including H. pylori infection, small bowel bacterial overgrowth, and systemic autoimmune disorders 1
HLA Testing (Limited Role)
- HLA-DQ2/DQ8 testing has high negative predictive value (>99%) but should not be performed routinely 1
- Reserve HLA testing for: patients with equivocal histology, those already on gluten-free diet without prior testing, discrepant serology and histology, or when original diagnosis is questioned 1
Management
Gluten-Free Diet: The Cornerstone
Strict adherence to a gluten-free diet with intake of less than 10 mg gluten per day is the primary treatment and must be maintained lifelong 1:
- Most patients experience substantial and rapid improvement of symptoms within days to weeks, with mean time to diarrhea resolution of 4 weeks 3
- A gluten-free diet decreases excess risk of adverse fetal outcomes and lymphoma 1
- Patients may commence gluten-free oats at diagnosis 1
- Referral to an expert dietitian is essential for education on hidden gluten sources, cross-contamination, and balanced nutrition 4, 5
Monitoring and Follow-Up
Follow-up serology should be performed at 6 months, 12 months after diagnosis, and yearly thereafter 1:
- Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure 1
- Negative serology does NOT guarantee mucosal healing—the test has limited sensitivity for detecting continued injury 1
Non-Responsive Celiac Disease (4-30% of Patients)
When symptoms persist despite gluten-free diet, follow this systematic approach 1:
- Confirm the original diagnosis by reviewing biopsy, serology, and HLA status
- Assess dietary adherence with expert dietitian—inadvertent gluten exposure is the most common cause 1
- Exclude alternative diagnoses: Giardia/parasites, microscopic colitis, small intestinal bacterial overgrowth (SIBO), exocrine pancreatic insufficiency, lactose intolerance, fructose intolerance 1
- Perform follow-up biopsy to assess for mucosal healing and exclude refractory celiac disease 1
- Consider small bowel imaging if abdominal pain, fever, obstruction, anemia, GI bleeding, or unexplained weight loss present 1
Refractory Celiac Disease
- Defined as persistent symptoms and villous atrophy despite strict gluten-free diet for >12 months 1, 5
- Type I (good prognosis): normal T-cell markers, no monoclonality 1
- Type II (poor prognosis): aberrant T-cells with risk of enteropathy-associated T-cell lymphoma 1
- Requires gastroenterologist management with consideration of immunosuppressive therapy 4, 5
Nutritional Supplementation
Address common deficiencies at diagnosis and during follow-up 6: