What are the symptoms and treatment options for a patient with suspected celiac disease and a history of lymphocytic gastritis?

Celiac Disease: Clinical Presentation and Diagnostic Approach

Clinical Symptoms and Presentation

Celiac disease presents with a highly variable clinical spectrum, ranging from completely asymptomatic to severe gastrointestinal and extraintestinal manifestations, with the majority of patients now presenting without classic GI symptoms. 1

Gastrointestinal Manifestations

• Diarrhea or constipation are common but not universal GI symptoms 2
• Abdominal pain, bloating, and weight loss may occur but are frequently absent 3
• Dyspeptic symptoms are common presenting complaints 4
• The proportion of newly diagnosed patients with malabsorptive symptoms has decreased over time, while non-classical and asymptomatic presentations have become predominant 1

Extraintestinal Manifestations

• Dermatitis herpetiformis is a specific skin manifestation 2
• Iron deficiency anemia (present in 2-6% of unexplained cases) 3
• Osteoporosis or premature bone loss 5
• Fatigue, irritability, and inability to concentrate 3
• Unexplained elevated liver transaminases 5

Asymptomatic Presentation

• Silent celiac disease is now recognized as at least as common as classic gastrointestinal presentations, affecting approximately 1% of the population with only 24% diagnosed 1
• High-risk groups frequently present without symptoms and are detected only through screening 1

Associated Conditions and High-Risk Populations

Screen the following high-risk groups even in the absence of symptoms:

• First-degree relatives (7.5-10% prevalence) 1, 5
• Type 1 diabetes (2-10% prevalence) 1, 5
• Autoimmune thyroid disease (3% prevalence) 1, 5
• Down syndrome (5.5% prevalence) 1, 5
• Turner syndrome (6.3% prevalence) 1
• Autoimmune liver disease 1

Lymphocytic Gastritis Association

Lymphocytic gastritis occurs in 16-33% of celiac disease patients and is strongly associated with the condition. 4, 6, 7

• All patients with lymphocytic gastritis and celiac disease are Helicobacter pylori negative 4
• The severity of intraepithelial lymphocytosis is greater in the antrum than body in 83% of celiac-associated cases, which distinguishes it from H. pylori-associated lymphocytic gastritis 6
• 94% of patients show improvement in gastritis after gluten-free diet, and 82% show improvement in duodenal lesions 4
• Chronic active gastritis and chronic inactive gastritis are also significantly more common in celiac disease (present in 31.5% and 32.9% respectively), but these do not respond to gluten-free diet 4, 7

Diagnostic Algorithm

Step 1: Initial Serologic Testing

Order IgA tissue transglutaminase (tTG-IgA) with total IgA level as the first-line test (sensitivity 90.7%, specificity 87.4% in adults) 2, 5

• Patients must consume at least 10g of gluten daily for 6-8 weeks before testing to avoid false-negative results 2, 5
• Measure total IgA simultaneously because IgA deficiency occurs 10-15 times more frequently in celiac patients (1-3% prevalence) and causes falsely negative results 2, 5

Step 2: Manage IgA Deficiency if Present

If IgA is low or deficient, immediately order IgG-based testing:

• IgG deamidated gliadin peptide (DGP-IgG) is preferred (93.6% sensitivity, 99.4% specificity) 3, 5
• IgG tissue transglutaminase (tTG-IgG) is an alternative but has lower accuracy (40.6-84.6% sensitivity) 3, 5

Step 3: Confirmatory Serology

If tTG-IgA is positive, confirm with endomysial antibody (EMA) testing (99.6% specificity in adults) 2, 3, 5

• When tTG-IgA exceeds 10× the upper limit of normal combined with positive EMA, the positive predictive value is virtually 100% 2, 3

Step 4: Endoscopic Confirmation

Upper endoscopy with duodenal biopsy is mandatory to confirm diagnosis in adults, even with highly positive serology 2, 8

• Obtain at least 6 biopsy specimens: 1-2 from duodenal bulb and 4-6 from the second part of duodenum or beyond 2, 5
• Request thorough histological analysis with Marsh classification, counting of lymphocytes per HPF, and morphometry 2
• Specimens must be properly oriented for accurate histologic interpretation 3

Step 5: Consider HLA Testing in Specific Scenarios

HLA-DQ2/DQ8 testing is not routine but has value in select situations:

• Negative HLA-DQ2 and DQ8 has >99% negative predictive value and essentially rules out celiac disease 2, 5
• Use when serology and histology are discordant 2
• Use when patient already started gluten-free diet before diagnostic workup 2
• Use in patients with duodenal lymphocytosis but no villous atrophy and negative serology 2

Treatment: Gluten-Free Diet

Initiate strict gluten-free diet immediately after biopsy confirmation 2, 5

• Refer to a registered dietitian experienced in celiac disease management 3, 5
• Never start gluten-free diet before completing diagnostic workup, as this leads to false-negative serology and inconclusive biopsies 2

Monitoring After Diagnosis

Follow-up serology schedule:

• At 6 months after starting gluten-free diet 2, 3
• At 12 months after diagnosis 2, 3
• Annually thereafter 2, 3

Persistently positive serology indicates ongoing intestinal damage and gluten exposure 2, 3

Patients with persistent or relapsing symptoms should undergo repeat endoscopic biopsies to determine mucosal healing, even with negative serology 2

Critical Pitfalls to Avoid

• Do not rely on symptoms alone or symptom response to gluten-free diet for diagnosis, as this cannot differentiate celiac disease from non-celiac gluten sensitivity and has very low positive predictive value 2, 3
• Do not reduce or avoid gluten before diagnostic testing, as this reduces sensitivity of both serology and biopsy 2
• Do not skip biopsy confirmation in adults based on serology alone, even with highly positive antibodies 2
• Do not assume negative serology rules out celiac disease in patients with duodenal lymphocytosis or villous atrophy—proceed with full diagnostic workup including HLA testing 2, 9