CELIAC DISEASE/ CELIAC SPRUE/ NONTROPICAL SPRUE/
GLUTEN-SENSITIVE ENTEROPATHY
Celiac disease is characterized by malabsorption of nutrients in the small intestine, loss of intestinal villus structures on biopsy, and resolution of both symptoms and biopsy abnormalities following a gluten free diet. An abnormal T-cell response to dietary gluten is the cause of this disease. Large scale studies have revealed that celiac disease is extremely common with a prevalence between 1 in 130 to 1 in 300 persons in European populations. However, this disorder is common worldwide with the exception of Japanese, populations. First and second-degree relatives of patients have a higher prevalence of disease and should be tested even when asymptomatic. A high prevalence of disease is also noted among patients with type 1 diabetes mellitus, anemia (iron, folate and B12 deficient types), osteoporosis, infertility, rheumatoid arthritis, systemic lupus erythematosus, and Down's syndrome.
Symptoms are often subtle and varied so a high index of suspicion is needed to make the diagnosis. Gastrointestinal symptoms (generally diarrhea) are not always present but most patients will have hyperdefecation (rarely, constipation may be present). The hyperdefecation or diarrhea may be the result of steatorrhea, secondary lactose intolerance, bile acid malabsorption, or increased fluid secretions from intestinal crypts. Other symptoms include pedal edema (secondary to protein malabsorption), digital clubbing, ecchymosis (secondary to vitamin K malabsorption), short stature, weight loss, weakness, osteopenia or osteoporosis, symptoms of hypocalcemia (paresthesias, muscle cramps, tetany), peripheral neuropathy, myopathy, cerebellar ataxia, myoclonus, cerebral atrophy, dementia, aphthous stomatitis, infertility(both male and female patients), a high incidence of spontaneous abortions, and dermatitis herpetiformis. Hyposplenism may occur and is sometimes reversible with strict adherence to a gluten free diet. Malignancies associated with celiac disease include non-Hodgkin’s lymphoma, squamous cell carcinoma of the esophagus and adenocarcinoma of the small intestine.
Dermatitis herpetiformis is a characteristic lesion of celiac disease and its presence confirms the diagnosis. The rash is characterized by symmetric, intensely pruritic, erythematous blisters on the face, elbows, back, buttocks, and knees.
Different forms of this disease include symptomatic, asymptomatic (usually found during mass serologic screenings or when a relative is diagnosed), and latent (positive serologic tests but normal histology on small bowel biopsy). It is believed that persons with the latent form have not yet developed celiac disease but will with continued gluten exposure.
Laboratory abnormalities include anemia secondary to either malabsorption of iron, folate or vitamin B12. Consider the diagnosis in patients with anemia without an identifiable etiology. Thrombocytosis is another abnormality that may be noted on CBC examination along with the presence of Howell-Jolly bodies (small, round, dark staining nuclear fragments noted in RBCs secondary to asplenia). Vitamin K deficiency secondary to malabsorption may cause a prolongation of the PT. Hypocalcemia may be severe and symptomatic with resultant osteoporosis or secondary hyperparathyroidism. Elevated transaminase levels are also commonly encountered in celiac disease patients. In fact, patients with persistent, mild transaminasemia without an identifiable etiology after preliminary biochemical testing should undergo a diagnostic evaluation to eliminate underlying celiac disease. Associated diseases include glomerulonephritis, fatty liver, primary sclerosing cholangitis, and primary biliary cirrhosis.
Endoscopic evaluation with biopsy of the small intestine allows evaluation of the mucosa directly. The characteristic histopathologic findings include a flattened mucosa, an expanded lamina propria, and an infiltration of the epithelium with lymphocytes. Normal findings on small bowel biopsy exclude the diagnosis (if positive serologies consider the latent form). Biopsy specimens demonstrating the characteristic changes are not diagnostic as several other diseases may be associated with these findings such as hypogammaglobulinemia, tropical sprue, intestinal lymphoma, Zollinger-Ellison syndrome, eosinophilic gastroenteritis, Crohn’s disease, and bacterial overgrowth. Resolution of symptoms and mucosal pathology in response to a gluten free diet (gluten is a water-insoluble protein found in certain grains) is diagnostic; however, months and even years may be required for complete histologic resolution.
Several antibody titers may be helpful in establishing the diagnosis. IgA antiendomysial antibodies, and IgA anti-tissue transglutaminase antibodies may be elevated with celiac disease. IgA anti-tissue transglutaminase is an efficient screening test. Because IgA deficiency is extremely common in patients with celiac disease, a serum IgA level should be determined. If IgA deficiency is present, then IgG antigliadin antibody testing may be helpful or the patient should undergo EGD with multiple (up to 5) biopsies of the duodenum because intestinal pathology may randomly distributed.
Therapy is a strict gluten free diet. The major sources of gluten are wheat, barley, rye, and oats. It is important to note that many tablet form medications contain with wheat starch and must therefore be avoided. If a patient does not respond to a gluten free diet, then supplementation with pacreatic enzyme supplements may prove beneficial. If bacterial overgrowth is suspected or diagnosed, a course of antibiotics is warranted. And some patients with refractory disease may require treatment with corticosteroids or immunosuppressive medications. Patients are at an increased risk of malignancies particularly of the GI tract and bone disease (osteoporosis) and should be screened accordingly. Dermatitis herpetiformis can be treated with dapsone therapy.