Celiac Disease
Definition
- Chronic enteritis secondary to gluten sensitivity
Alternate/Historical Names
- Celiac sprue
- Coeliac disease
- Gluten sensitive enteropathy
- Non-tropical sprue
Diagnostic Criteria
- Villous atrophy in small intestine
- May be variable and patchy
- Most symptomatic patients have total villous atrophy
- Defined as completely flattened villi
- Partial atrophy more common in pre-symptomatic or post-treatment patients or in relatives being screened
- Increased intraepithelial lymphocytes in small intestine may be seen with or without atrophy
- Cutoff varies by location
- Duodenum >30 / 100 enterocytes
- Alternative proposed is 6-12 / 20 enterocytes at the tips of villi
- Jejunum >40 / 100 enterocytes
- Occasionally seen in stomach and large intestine
- Duodenum >30 / 100 enterocytes
- T cell phenotype
- CD2+, CD3+, CD8 70-90%
- Gamma delta T cell receptor
- CD3 stain is useful for identification and counting
-
Intraepithelial lymphocytes evenly distributed from bottom to top of crypts or increased at tops
-
Normal distribution is decreasing from bottom to top
- Villi must be well oriented to be certain that what appears to be the top is not a semi-tangentially cut section of mid-villus
-
Normal distribution is decreasing from bottom to top
- Identification of an abnormal distribution or of more than rare lymphocytes on H&E is a clue that it may be worth staining and counting cells
- Increased intraepithelial lymphocytes in the absence of villus atrophy is suggestive of latent or partially treated celiac disease but not specific, as it can be seen in:
- Infections (Giardia, Helicobacter, Cryptosporidium, viruses)
- Food allergy
- Drug reactions (NSAIDS)
- Immune system abnormalities
- Inflammatory bowel disease
- Lymphocytic colitis and gastritis
- Morbid obesity (Harpaz)
- Chronic inflammatory infiltrate in lamina propria
- Lymphocytes, plasma cells and eosinophils most common
- Neutrophils may be seen in lamina propria and crypts (Moran 2012)
- More common in children than adults (56 vs 28%)
- Correlates with disease activity
- Other diagnoses such as infection must be ruled out
- Crypt hyperplasia
- Normal villus:crypt length ratio is 3-5:1
- Mitotic figures may be numerous
- Changes similar to the above may occasionally be seen in the stomach and large intestine
- Biopsy is required for diagnosis
- Distal duodenum is best as it avoids most other inflammatory processes
- Biopsy is required to assess the response to dietary gluten restriction
- Villous atrophy may be only partial or absent
- Intraepithelial lymphocytes and lamina propria infiltrate may be decreased or absent
- Complete return to normal may take years
- Histology of refractory disease is not as well described
- Defined as loss of clinical response to gluten free diet
- Mucosal atrophy and thinning
- Increased subepithelial collagen layer (collagenous sprue)
- Decreased CD8 expression by T cells
- Development of ulcerative jejunoileitis
- Development of enteropathy type T cell lymphoma can cause refractory disease
- The Modified Marsh Classification of histologic findings has been used to grade celiac disease
- Simplified systems (Corazza, Roberts, Ensari) may be more reproducible
- Grade A/Type 1: increased intraepithelial lymphocytes but no villous atrophy
- Grade B1/Type 2: villi still present but shortened
- Grade B2/Type 3: complete villous atrophy
- Simplified systems (Corazza, Roberts, Ensari) may be more reproducible
-
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting, last update: 11/11/09, 12/3/14
