- Pathogenesis. A number of disorders of varying etiology affect the mucosa of the small intestine, section intravenous.C.3). Because all ingested foodstuffs are assimilated across the small-bowel mucosa, disorders that affect the mucosa have the potential for causing malabsorption of fat, protein, carbohydrate, vitamins, and minerals. Whether malabsorption is clinically significant depends on the site and extent of involvement. For example, in celiac sprue (gluten-sensitive enteropathy), the lesion begins first in the proximal intestine and extends distally. Because iron, calcium, and folate are absorbed preferentially in the proximal small bowel, these nutrients may not be absorbed normally in patients with celiac sprue. On the other hand, because Crohn’s disease most often affects the distal ileum, which is the site of vitamin B12 and bile acid absorption, patients with Crohn’s disease may have vitamin B12 and bile acid deficiency.
- Diagnosis.The small-bowel x-ray series usually is abnormal in small-bowel mucosal disease. It may be nonspecifically abnormal, showing dilatation of the bowel and dilution of the barium, such as in celiac sprue. In contrast, infiltrative disorders, such as Whipple’s disease, lymphoma, or amyloidosis, cause thickening of the mucosal folds. Irregular mucosal contour and narrowed loops may suggest Crohn’s disease.
Small-bowel biopsy. When small-bowel mucosal disease is suspected, the question often is when to perform the small-bowel biopsy. Some physicians proceed directly to biopsy in the clinical setting of apparent panmalabsorption and an abnormal small-bowel x-ray series without clinical suspicion of pancreatic disease. Others first order a xylose tolerance test to confirm mucosal disease and obtain a 72-hour stool fat collection to quantitate the steatorrhea. A Schilling test usually is not performed. The small-bowel biopsy may or may not be diagnostic, section intravenous).
Celiac sprue. The diagnosis of celiac sprue is suspected on clinical grounds, strengthened by a small-bowel biopsy that shows the typical lesion, and confirmed by the patient’s response to a gluten-free diet. Serologic tests are quite sensitive for the diagnosis of celiac sprue. In patients with this disorder it is thought that gliadin, a protein derived from dietary gluten, is thought to form an immunogenic complex with tissue trans-glutaminase, an enzyme involved in tissue injury response. In genetically susceptible patients, this gliadin-trans-glutaminase complex forms the substrate for antigliadin, antiendomysial, and anti-trans-glutaminase antibiotics. The resulting T-cell response mediates intestinal mucosal damage. Serologic measurement of IgA antigliadin antibodies, antiendomysial antibodies, and IgA anti+-TG antibodies by enzyme-linked immunosorbent assays provides a highly sensitive and specific means of diagnosing celiac sprue. Because selective IgA deficiency is as common disorder among patients with celiac sprue, IgG antigliadin antibodies or serum IgA levels are also routinely obtained.
Other mucosal disorders. The mucosal lesion of Whipple’s disease is characterized by blunted villi that are distended by dense accumulations of periodic acid – Schiff– positive macrophages. These periodic acid – Schiff-positive macrophages contain the etiologic agent of Whipple’s disease: Tropheryma Whippelii, a gram-positive actinomycete. T. Whippelii has also been isolated from pleural fluid, vitrous sample, and peripheral blood mononuclear cells by polymerase chain reaction.
Whipple’s disease is a systemic disorder that usually presents with weight loss, cough, fever, diarrhea, hypotension, abdominal swelling, anemia, mental status changes. Periodic acid – Schiff-positive macrophages may be found in the small bowel, pericardium, endocardium, synovia, lymph nodes, lung, brain, meninges, uvea, retina, and optic nerves. The disease in some instances may present as a sarcoidlike syndrome and involve the mediastinal nodes.
Other small-bowel mucosal disorders include abetalipoproteinemia, which is identified by villous epithelial cells that contain large fat vacuoles. The absence of plasma cells suggests agammaglobulinemia. Other disorders may or may not be evident on mucosal biopsy, section intravenous.C.3).
A discussion of the clinical management of all the small-bowel mucosal disorders is beyond the scope of this book. The reader is referred to standard textbooks of medicine and gastroenterology.
Celiac sprue. The treatment of celiac sprue is primarily the rigorous restriction of all dietary gluten. The patient must avoid all wheat, barley, rye, and oats. Rice, corn, soy, and the flours of these grains are acceptable. Sprue patients must also avoid many commercially prepared foods, such as some brands of ice cream, some desserts, and meats that contain wheat fillers. Even some vitamin and drug preparations are enclosed in capsules that contain small amounts of gluten, which may be sufficient to produce mucosal injury in some patients. Adjunctive treatment of sprue may include vitamin, calcium, and iron supplements.
Whipple’s disease. Patients with Whipple’s disease should receive procaine penicillin G, 1.2 million units per day intramuscular injection or intravenously, plus streptomycin 1 g per day intramuscular for 2 weeks, followed by trimethoprim/sulfamethoxazole double-strength twice daily for 1 year.
The mucosal lesion in other disorders, such as intestinal lymphoma, parasitic infestations, and Crohn’s disease, responds to treatment directed at the underlying disease. If clinically significant steatorrhea persists, restriction of dietary fat is indicated. Supplemental vitamins and minerals may be necessary.