Woman With Celiac Sprue and Primary Immunodeficiency

A 34-year-old white woman presents with a 4-month history of diarrhea, with bulky, foul-smelling stools; flatulence; diffuse abdominal discomfort; and episodic nausea and vomiting. She has lost 13.5 kg (30 lb) during this period. The patient has had no fever, and her medical, family, and travel history are unremarkable. Physical examination results and vital signs are normal.

Laboratory values include hemoglobin, 10.5 g/dL (normal, 12 to 16 g/dL); mean corpuscular volume, 73 fL (normal, 80 to 100 fL); and iron, 19 µg/dL (normal, 46 to 178 956;g/dL). Routine stool cultures are negative for ova and parasites, leukocytes, and occult blood. White blood cell count, erythrocyte sedimentation rate, and serum chemistries are normal. Serologic markers for celiac disease are within normal limits: antigliadin IgA, 4 units (normal, 0 to 20 units); antigliadin IgG, 19 units (normal, 0 to 20 units); and endomysium IgA, 2 units (normal, 0 to 20 units).

The results of a colonoscopy are normal; however, upper endoscopy reveals a "scalloped" appearance of the small bowel (Figure 1). Biopsy of the small bowel reveals severe villous blunting, crypt hyperplasia, and a lymphocytic infiltration of the lamina propria, consistent with celiac disease (Figure 2).

Because the serologic markers for celiac disease are IgA- and IgG-based, quantitative serum levels of these immunoglobulins are measured. A severe selective IgA deficiency—IgA less than 5 mg/dL, (normal, 66 to 344 mg/dL)—is detected. Levels of IgG and IgM are normal. The deficiency in IgA would explain why the IgA-based serologic markers were negative for celiac disease. Although the IgG antigliadin antibody level was also normal, it was at the upper limit of the range. The patient starts to follow a gluten-free diet. Within 3 weeks, she is asymptomatic.

CELIAC SPRUE AND SELECTIVE IgA DEFICIENCY

Selective IgA deficiency. This is the most common primary immunodeficiency; 1 in 700 persons are affected. ¹ Although most persons with selective IgA deficiency remain asymptomatic, a small percentage experience recurrent infections. These include frequent infections of the upper and lower respiratory tracts and the middle ear.² In addition, IgA deficiency is associated with autoimmune disorders, including celiac disease, Hashimoto thyroiditis, Sjögren syndrome, and systemic lupus erythematosus. Eight percent of patients with IgA deficiency have celiac disease; however, only 2% of patients with celiac disease have IgA deficiency.^3,4

Celiac sprue. This disease is caused by an abnormal immune-system response to dietary gluten, which results in damage to the mucosa of the small intestine. The damaged mucosa heals when gluten is removed from the diet and relapses when gluten is reintroduced. The principle sources of dietary gluten are wheat, rye, and barley. Although classically a disease of infants, celiac sprue often occurs later, between the ages of 10 and 40 years.

Patients may describe bulky, foul-smelling stools and floating stools that are caused by steatorrhea. The consequences of malabsorption include growth failure, weight loss, and anemia. Serum antigliadin and endomysial antibody levels are frequently elevated in patients with untreated celiac disease and have been used as markers in serologic screening tests. Serum IgA endomysial antibody testing has the highest diagnostic accuracy, with a specificity of 97% to 100% and a sensitivity of 85% to 99%. Serum IgA antigliadin antibody testing has a sensitivity of 80% to 90% and a specificity of 85% to 95%. Serum IgG antigliadin antibody testing has a sensitivity of 75% to 85% and a specificity of 75% to 90%.⁵ The serum level of tissue transglutaminase has been touted as the most sensitive and specific marker for celiac sprue.

Testing is based on IgA antibodies to tissue transglutaminase, which is believed to be the autoantigen to which endomysial antibodies react. Studies have shown that the specificity of the antitransglutaminase test is comparable to that of the antiendomysial test. However, some investigators have observed that the antitransglutaminase test is more sensitive; it detects celiac sprue in 98% to 100% of affected patients.⁶

THE "TAKE-HOME" MESSAGE
If you strongly suspect celiac sprue but the patient’s serum antigliadin and endomysial antibody levels are normal, a small-bowel biopsy is essential for diagnosis. If the biopsy result is consistent with celiac sprue and the patient’s symptoms respond to a gluten-free diet, consider a concomitant selective IgA deficiency and order a quantitative immunoglobulin panel.