Can someone have celiac disease without villous (small intestinal mucosal) atrophy?

Can Someone Have Celiac Disease Without Villous Atrophy?

Yes, celiac disease can exist without villous atrophy, but this represents "probable celiac disease" rather than definitive celiac disease according to current diagnostic criteria. 1

Diagnostic Framework

Definitive vs. Probable Celiac Disease

For a definitive diagnosis of celiac disease in adults, villous atrophy is required. 1 However, the British Society of Gastroenterology explicitly recognizes that lesser degrees of intestinal damage may also indicate celiac disease. 1

Specifically, patients with:

• Positive celiac serology (IgA-EMA, tissue transglutaminase, or IgG-DGP)
• Increased intraepithelial lymphocytes (≥25 IELs per 100 enterocytes)
• No villous atrophy

...may be classified as having "probable celiac disease" and should be offered a trial of gluten-free diet to support the diagnosis. 1 HLA-DQ2/DQ8 testing can further aid diagnosis in these equivocal cases. 1, 2

Clinical Significance of Mild Enteropathy

Celiac disease without villous atrophy is not a benign condition and requires treatment. 3 Research demonstrates that patients with mild enteropathy (increased IELs without villous atrophy) experience:

• Similar rates of gastrointestinal symptoms (70% vs 70%) 3
• Similar rates of extraintestinal manifestations (57% vs 66%) 3
• Significant osteopenia risk (5% vs 22%, though lower than those with atrophy) 3
• Anemia (29% vs 42%) 3
• Metabolic abnormalities including folate deficiency, hypocalcemia, and hyperparathyroidism 3

Diagnostic Algorithm for Suspected Celiac Disease Without Villous Atrophy

Step 1: Confirm Adequate Biopsy Sampling

• Obtain at least 4-6 biopsies from the second portion of duodenum and duodenal bulb 2, 4
• Villous atrophy can be patchy; a minimum of 3 biopsies (including duodenal bulb) detects 100% of cases 4
• Have an experienced GI pathologist confirm proper orientation and assess for ≥25 IELs per 100 enterocytes 1, 2

Step 2: Verify Serologic Testing

• Confirm positive IgA tissue transglutaminase (tTG) antibodies 2
• Measure total IgA level to exclude IgA deficiency 2
• Consider IgA endomysial antibodies (EMA) for additional specificity 2
• If IgA deficient, obtain IgG-based tests (IgG-tTG, IgG-DGP) 1, 2

Step 3: Assess HLA Status

• HLA-DQ2 or HLA-DQ8 testing has >99% negative predictive value 2
• Absence of both alleles virtually excludes celiac disease 2
• Approximately 95% of celiac patients have HLA-DQ2, and 5% have HLA-DQ8 2

Step 4: Trial of Gluten-Free Diet

If serology is positive, IELs are elevated (≥25/100 enterocytes), and HLA is compatible, initiate a 6-month trial of strict gluten-free diet with dietitian support. 1, 5 Clinical and histologic response to gluten-free diet confirms the diagnosis. 1, 2

Monitor for:

• Symptom resolution 6
• Normalization of celiac antibodies 6
• Repeat biopsy at 12-24 months to assess histological improvement 5

Critical Pitfalls to Avoid

Do not dismiss patients with positive serology and increased IELs simply because villous atrophy is absent. 1, 6 Early research from 2001 demonstrated that patients with only minor mucosal lesions and increased γδ+ intraepithelial lymphocytes showed clinical, histological, and serological recovery on gluten-free diet, with significant risk of osteopenia arguing for dietary treatment. 6

Do not rely on duodenal bulb biopsies alone, as they may be compromised by Brunner's glands or peptic changes and can miss patchy disease. 2, 4

Do not start gluten-free diet before completing diagnostic workup, as this leads to false-negative serology and inconclusive biopsies. 2

Differential Diagnosis Considerations

Before diagnosing probable celiac disease, exclude other causes of increased IELs without villous atrophy (lymphocytic duodenosis): 1

• Medications: NSAIDs, PPIs, olmesartan, mycophenolate mofetil 1, 2, 7
• Infections: Helicobacter pylori gastritis, Giardiasis, post-infectious enteropathy 1, 2
• Autoimmune conditions: Common variable immunodeficiency, autoimmune enteropathy 1
• Other: Small intestinal bacterial overgrowth, food protein intolerances 1, 5

Notably, 16% of cases initially presenting as lymphocytic duodenosis were ultimately found to have celiac disease in one study. 1

Summary of Evidence Quality

The British Society of Gastroenterology guidelines (2014) provide the most comprehensive framework, explicitly stating that "lesser degrees of damage (≥25 IELs but no villous atrophy) may also indicate CD" and classifying these as "probable celiac disease." 1 This is supported by the American Gastroenterological Association's recognition that villous atrophy is required for definitive diagnosis but acknowledging that earlier stages exist. 2 Research evidence consistently demonstrates that these patients have significant clinical disease requiring treatment. 6, 3