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Celiac sprue
is an immunologically mediated disease in genetically susceptible
people caused by intolerance to gluten, resulting in mucosal inflammation,
which causes malabsorption. Symptoms usually include diarrhea and
abdominal discomfort. Diagnosis is by small-bowel biopsies showing characteristic
though not specific pathologic changes of villous atrophy that resolve
with a strict gluten-free diet.
(See
also the Agency for Healthcare Research and Quality's evidence report
summary on celiac disease.)
Etiology
Celiac sprue is a hereditary disorder caused by sensitivity to the gliadin fraction of gluten, a protein found in wheat; similar proteins are present in rye and barley. In a genetically susceptible person, gluten-sensitive T cells are activated when gluten-derived peptide epitopes are presented. The inflammatory response causes characteristic mucosal villous atrophy in the small bowel.
Epidemiology
Celiac sprue mainly affects whites of northern European descent. Prevalence estimates based on serologic screens (sometimes confirmed by biopsy) indicate the disorder is present in about 1/300 in Europe and perhaps 1/250 in the US overall (but there may be significant variation among regions in the US).
The disease affects about 10 to 20% of first-degree relatives. Female-to-male ratio is 2:1. Onset is generally in childhood but may occur later.
Symptoms and Signs
The clinical presentation varies; no typical presentation exists. Some patients are asymptomatic or have only signs of nutritional deficiency. Others have significant GI symptoms.
Celiac sprue can manifest in infancy and childhood after introduction of cereals into the diet. The child has failure to thrive, apathy, anorexia, pallor, generalized hypotonia, abdominal distention, and muscle wasting. Stools are soft, bulky, clay-colored, and offensive. Older children may present with anemia or failure to grow normally.
In adults, lassitude, weakness, and anorexia are most common. Mild and intermittent diarrhea is sometimes the presenting symptom. Steatorrhea ranges from mild to severe (7 to 50 g fat/day). Some patients have weight loss, rarely enough to become underweight. Anemia, glossitis, angular stomatitis, and aphthous ulcers are usually seen in these patients. Manifestations of vitamin D and Ca deficiencies (eg, osteomalacia, osteopenia, osteoporosis) are common. Both men and women may have reduced fertility.
About 10% have dermatitis herpetiformis, an intensely pruritic papulovesicular rash that is symmetrically distributed over the extensor areas of the elbows, knees, buttocks, shoulders, and scalp. This rash can be induced by a high-gluten diet. Celiac sprue is also associated with diabetes mellitus, autoimmune thyroid disease, and Down syndrome.
Diagnosis
The diagnosis is suspected clinically and by laboratory abnormalities suggestive of malabsorption. Family incidence is a valuable clue. Celiac sprue should be strongly considered in a patient with iron deficiency without obvious GI bleeding.
Confirmation requires a small-bowel biopsy from the second portion of the duodenum. Findings include lack or shortening of villi (villous atrophy), increased intraepithelial cells, and crypt hyperplasia. However, such findings can also occur in tropical sprue, severe intestinal bacterial overgrowth, eosinophilic enteritis, lactose intolerance, and lymphoma.
Because biopsy lacks specificity, serologic markers can aid diagnosis. Anti-tissue transglutaminase antibody (AGA) and anti-endomysial antibody (EMA-an antibody against an intestinal connective tissue protein) each have sensitivity and specificity greater than 90%. These markers can also be used to screen populations with high prevalence of celiac sprue, including first-degree relatives of affected patients and patients with diseases that occur at a greater frequency in association with celiac sprue. If either test is positive, the patient should have a diagnostic small-bowel biopsy. If both are negative, celiac sprue is extremely unlikely. These antibodies decrease in titer in patients on a gluten-free diet and thus are useful in monitoring dietary compliance.
Other laboratory abnormalities often occur and should be sought. These include anemia (iron-deficiency anemia in children and folate-deficiency anemia in adults); low albumin, Ca, K, and Na; and elevated alkaline phosphatase and PT.
Malabsorption tests are not specific for celiac sprue. If done, common findings include steatorrhea of 10 to 40 g/day and abnormal results with d‑xylose and (in severe ileal disease) Schilling tests.
Prognosis
Mortality is 10 to 30% without a gluten-free diet. With proper diet, mortality is < 1%, mainly in adults who have severe disease at the outset. Complications include refractory sprue, collagenous sprue, and intestinal lymphomas. Intestinal lymphomas affect 6 to 8% of patients with celiac sprue, usually presenting after 20 to 40 yr of disease. The incidence of other GI cancers (eg, carcinoma of the esophagus or oropharynx, small-bowel adenocarcinoma) also increases. Adherence to a gluten-free diet can significantly reduce the risk of cancer.
Treatment
Treatment is a gluten-free diet (avoiding foods containing wheat, rye, or barley). Gluten is so widely used (eg, in commercial soups, sauces, ice creams, hot dogs) that a patient needs a detailed list of foods to avoid. Patients are encouraged to consult a dietitian and join a celiac support group. The response to a gluten-free diet is usually rapid, and symptoms resolve in 1 to 2 wk. Ingesting even small amounts of food containing gluten may prevent remission or induce relapse.
Small-bowel biopsy should be repeated after 3 to 4 mo of a gluten-free diet. If abnormalities persist, other causes of villous atrophy (eg, lymphoma) should be considered. Lessening of symptoms and improvement in small-bowel morphology is accompanied by a decrease in AGA and EMA titers.
Supplementary vitamins, minerals, and hematinics may be given, depending on the deficiencies. Mild cases may not require supplementation, whereas severe cases may require comprehensive replacement. For adults, replacement includes ferrous sulfate 300 mg po once/day to tid, folate 5 to 10 mg po once/day, Ca supplements, and any standard multivitamin. Sometimes children (but rarely adults) who are seriously ill on initial diagnosis require bowel rest and TPN.
If a patient responds poorly to gluten withdrawal, either the diagnosis is incorrect or the disease has become refractory. Corticosteroids can control symptoms in the latter case.
Last full review/revision January 2008 by Atenodoro R. Ruiz, Jr., MD
Content last modified January 2008
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