Celiac Disease
Differential Diagnosis
- Increased intraepithelial lymphocytes are not specific
- Tropical sprue
- Prolonged post-enteritis syndrome
- Autoimmune enteropathy
- Common variable immunodeficiency
- Food allergy
- Crohn disease
Increased intraepithelial lymphocytes in the absence of villus atrophy can also be seen in the following, which must be ruled out clinically
- Infections (Giardia, Helicobacter, Cryptosporidium, viruses)
- Food allergy
- Drug reactions (NSAIDS, chemotherapy)
- Immune system abnormalities (GVHD, autoimmune enteropathy, other autoimmune diseases)
- Confined to tropics
- Responds to anti-microbial therapy
- Lacks anti-endomysial antibodies
- History of preceding viral or bacterial gastroenteritis
- Usually infantile
| Celiac Disease | Autoimmune Enteropathy |
| Usually occurs in childhood or older | Usually begins under 6 months of age, but can occur in adults |
| Responds to gluten withdrawal | Refractory to gluten withdrawal |
| Anti-endomysial and - tissue transglutaminase antibodies | Anti-enterocyte antibodies |
| CD4 negative T cells predominate | CD4+ T cells predominate |
| Gamma delta T cell receptors predominate | Alpha beta T cell receptors predominate |
Some adult autoimmune enteropathy cases have been discovered in the workup of patients thought to have celiac disease but who do not respond to removal of gluten from the diet
| Celiac Disease | Common Variable Immunodeficiency – GI Involvement |
| Numerous plasma cells | Plasma cells frequently markedly decreased |
| Abnormal enterocyte maturation | Normal enterocyte maturation with brush border and goblet cells near lumen |
| Prominent villous atrophy | Villous atrophy may be mild to severe |
| Crypts hyperplastic | No crypt hyperplasia |
| Apoptosis not prominent | Apoptosis may be prominent in crypts |
| Anti-endomysial and - tissue transglutaminase antibodies | All antibodies generally depressed; humoral testing is not reliable in CVID |
| Food Enteropathy | Celiac Disease |
| May be predominantly eosinophilic infiltrate | Mixed lymphoplasmacytic and eosinophilic infiltrate |
| Usually presents very near birth | Usually presents in childhood to 30’s |
| Intraepithelial lymphocytes may be present but usually <40/HPF | Intraepithelial lymphocytes >40/HPF |
| Resolved by elimination of offending food from diet | Resolved by elimination of gluten from diet |
| Crohn Disease | Celiac Disease |
| Skip lesions predominate | Usually diffuse |
| Usually involves large intestine | Principal involvement is small intestine |
| Transmural inflammation | Mucosal inflammation |
| Granulomas may be seen | Granulomas absent |
| Anti-Saccharomyces antibody may be present | Anti-endomysial and - tissue transglutaminase antibodies |
