24: Celiac Disease

Clinical indications for serological testing

Chronic diarrhea with and without malabsorption
Irritable bowel syndrome
Unexplained weight loss
Iron deficiency anemia
Folate deficiency
Vitamin E or K deficiency
Osteoporosis
Hypocalcemia or vitamin D deficiency, secondary hyperparathyroidism, persistently low urinary calcium excretion
Unexplained elevation of transaminases
First-degree relatives of patients with celiac disease
Associated autoimmune diseases: type 1 diabetes, Sjögren syndrome, primary biliary cirrhosis
Down and Turner syndromes
Neurological disorders: unexplained peripheral neuropathy, epilepsy, and ataxia

Histology of the small intestine

To confirm the diagnosis of celiac disease, biopsy of the small intestinal mucosa is mandatory. With active disease, the endoscopic appearance of the duodenal mucosa is a loss of normal folds with scalloping. Different grades of enteropathy can be graded on microscopic examination.

Grade 0, or preinfiltrative, histology appears normal but can produce antibody to gluten and endomysium, is found in some cases of dermatitis herpetiformis, and characterizes latent disease. Grade 1 is an infiltrative lesion with increased epithelial lymphocytes but no villous atrophy; it usually does not produce gastrointestinal symptoms. Grade 2 is similar to grade 1 but the crypts are hypertrophic. The destructive grade 3 lesion is characterized by the typical flat mucosa of untreated celiac disease. With this finding, the total thickness of the mucosa is increased by crypt hyperplasia and lamina propria infiltration by plasma cells and lymphocytes. Epithelial cells lose their columnar appearance and become pseudostratified. Subtotal villous atrophy may be observed in milder disease or in disease that has been treated with a gluten-restricted diet. The grade 4 lesion is a hypoplastic histology that is not responsive to a gluten-free diet and is associated with nonneoplastic and neoplastic complications of celiac disease.

Other infectious or inflammatory diseases produce histological findings similar to celiac disease, including giardiasis, tropical sprue, collagenous sprue, HIV enteropathy, tuberculosis, radiation enteritis, Whipple disease, lymphoma and Crohn’s disease. Thus, a presumptive diagnosis of celiac disease should be supported by the response to a gluten-free diet.