Small Bowel Disease: Celiac Disease Clinical Findings
Celiac disease is a genetically determined immune reaction to dietary gluten that leads to damage of the proximal small bowel mucosa. In its classic full-blown form, celiac disease causes generalized malabsorption. Fortunately, most patients have a milder course, and many are asymptomatic or have subtle manifestations.
• Common among whites of European descent. Estimated incidence in the United States may be higher than 1:250.
• Can affect up to one-third of the population because it only afflicts those with HLA-DQ2 (95% of patients) or HLA-DQ8 (5% of patients).
• Only 25% of individuals with HLA-DQ2 or HLADQ8 develop Celiac disease, suggesting that other environmental and immunologic factors are necessary to manifest the phenotype.
• Celiac disease is secondary to a T-cell–mediated autoimmune response to glutens in the diet, affecting the intestinal submucosa of genetically susceptible individuals.
• Glutens are storage proteins that are present in wheat, barley, and rye but not in corn or rice. Glutens can be present in small amounts in oats as a contaminant.
• After ingestion of glutens, the partially digested gliadin peptides are processed by the antigen presenting cells in the lamina propria of the small bowel. Sensitized T-cells then activate B-cells to produce immunoglobulins, and other T-cells to produce inflammatory cytokines that damage the enterocytes. One target of this autoimmune response is tissue transglutaminase (Ttg), which is also necessary for the digestion of gliadin. Inactivation of Ttg intensifies the immune response because of the accumulation of incompletely digested gliadin. The detection of immunoglobulin A (IgA) antibodies against tissue transglutaminase is now the most valuable serologic marker for the diagnosis of celiac disease.1
• Celiac disease causes significant changes in the villous structure in the proximal small bowel. These changes can extend to the distal small bowel in severe cases.
• Varying degrees of villous blunting and atrophy, crypt hyperplasia and elongation, and infiltration of the lamina propria with lymphocytes and plasma cells are seen. The end result is the destruction of the intestine’s absorptive surface. Similar histologic findings are noted in other malabsorptive conditions such as tropical sprue, bacterial overgrowth, and Crohn’s disease among others.
• Celiac disease is one of the most commonly underdiagnosed diseases in the United States. On average, clinical clues are present for a decade before the diagnosis is made.
• Symptoms can become evident at any age throughout adulthood, but most patients present at age 10 to 40 years. Up to 40% of people with serologic markers of celiac disease remain asymptomatic.
• Significant malabsorption of multiple nutrients is usually seen in infants. Older children and adults present with a more subtle picture (anemia or bone disease), sometimes without any gastrointestinal symptoms. As patients advance in age the more likely the disease presents in an atypical fashion.
• Dermatitis herpetiformis (DH) is a pruritic papulovesicular rash found over the extensor surfaces of the trunk and extremities and responds to a gluten-restricted diet. The suggested mechanism is autoantibodies directed against epidermal transglutaminase. Up to 10% of patients with celiac disease have DH. Conversely, more than 85% of patients with DH have celiac disease.
• Laboratory abnormalities reflect the degree of intestinal pathology. Mild cases affecting the proximal small bowel may only cause iron deficiency anemia. More extensive involvement of the small bowel can lead to other types of anemia (folate and vitamin B12 deficiency), prolonged prothrombin time (vitamin K deficiency), and hypoalbuminemia. Mild elevation of aminotransferases is found in up to 40% of patients.