<<Disclaimer: Verify this information before applying it to your situation.>> Received this in the mail today. Don't know if it has been posted before. ************************************************************************* This article should be of some help. Regards. Copyright (c) 1994 Scientific American Medicine. Diseases of the Small Intestine Celiac Sprue Celiac disease of childhood and nontropical sprue (gluten-sensitive enteropathy) in adults define the spectrum of the celiac sprue syndrome. (ref 25) This disorder has been popularized by writings of experts on intestinal histology, but physicians rarely encounter it in their practices. Only three to six cases a year are seen at Stanford University Hospital, and several of these patients have had sprue for many years. Perhaps this observation reflects the fact that the prevalence of clinically manifest celiac sprue appears to have decreased during the past 10 to 15 years. (ref 26) Weight loss occurs in virtually all patients with celiac sprue, even though the patient usually has an adequate appetite; anorexia appears several months to a year later. Three quarters of all patients report abdominal distention, a sensation of bloating, and associated fatigue; 50 percent have anemia, usually of the megaloblastic type, attributable to folic acid deficiency. Although usually considered to be an important symptom, frank diarrhea is a major complaint in less than half of adult patients; it is usually intermittent and lasts less than six months. (ref 27) A small percentage of patients complain of nausea, tetany, cutaneous bleeding, glossitis, or psychiatric symptoms. All patients have an increase in the volume of stool, and there is usually an increase in stool frequency early in the course of the disease. Associated findings include a history of celiac disease as a child or a family history of celiac sprue. In fact, 25 percent of patients report such a family history. Celiac disease is often seen in females of short stature (a mean height of 150 cm, compared with 160 cm in the average population). Among celiac sprue patients, there is also an increased prevalence of blood type O and histocompatibility antigen HLA-B8 or DRw3. The presence of a particular HLA genotype in an individual is not sufficient in itself to cause celiac sprue. Siblings of patients with celiac sprue who share the HLA-B8 or DRw3 antigen have a low prevalence (about eight percent) of sprue. (ref 28, 29) Indeed, ingestion of gluten by normal monozygotic twins and siblings with HLA haplotypes identical to those of affected patients does not produce altered intestinal histology or malabsorption. This finding indicates that other factors in addition to a genetic predisposition and ingestion of gluten are required for expression of this small intestine disease. (ref 30) In recent years, patients have been identified earlier in the course of the disease. (ref 31) Fatigue or a mild anemia may be the initial subtle abnormality. Patients with a history that suggests small intestine malabsorption should undergo a quantitative fecal fat analysis, small intestine biopsy, xylose absorption test, and small intestine x-ray (see above). Small intestine histology is distinctly abnormal, with marked reduction in the villus height or total flattening of villi [see Figure 3]. Therapy is directed at removal of gluten from the diet; the -gliadin fraction of gluten is responsible for the clinical syndrome. The main sources of gluten are wheat, barley, oats, and rye. Therefore, foods that must be avoided are bread and most flours made from these grains. Beer, ale, vodka, and whiskey may contain significant amounts of gluten and should also be avoided. Easily overlooked sources of gluten include ice cream and other dairy products that may have had gluten added in processing, communion wafers, chewing gum, (ref 32) and drugs that contain gluten as an excipient. (ref 33) Within these limitations, patients may still have a balanced diet containing milk, cheese, eggs, meat, fish, poultry, yellow and green vegetables, potatoes, nuts, and chocolate. Substitution of rice, corn cereals, potato flour, and other starches for foods that contain the offending gluten makes it relatively easy for these patients to maintain adequate nutrition. Response to gluten exclusion is required for verification of the diagnosis, and the vast majority of patients with celiac sprue do respond relatively quickly. After one to three days of gluten exclusion, 30 percent of patients show marked improvement, and after one week to a month, another 50 percent improve. For 10 percent of patients, however, remission does not occur for one to two months, and another 10 percent may not show improvement for up to two years after gluten has been excluded from the diet. In patients who fail to respond to complete gluten restriction after three months, a trial of adrenocorticotropic hormone (ACTH) (20 to 40 U/day) or prednisone (20 to 40 mg/day) may be necessary. There have been reports of celiac sprue associated with inflammatory bowel disease in the small intestine or colon. (ref 34, 35) Ulcerative colitis or Crohn's disease may precede or follow celiac sprue by months or even years. Because symptoms of inflammatory bowel disease may mimic those of celiac sprue, it is worth noting that the two diseases can coexist. The most important complications of celiac sprue are the development of ulcerations (ref 36) and malignant disorders (ref 37, 38) of the small intestine. The risk of an intestinal malignant tumor appears to increase with the duration of the disease, and careful adherence to a gluten-free diet has not been shown to decrease that risk. Nonmalignant ulcerations tend to develop in patients with severe disease that is only partially responsive to gluten exclusion. Although prednisone has been used, surgical excision is frequently necessary, and patients with mucosal ulcerations are often less responsive to dietary restriction of gluten or to prednisone therapy than those without ulcers. Primary small intestine malignant tumors develop in 15 to 20 percent of celiac sprue patients; about half of those tumors are histiocytic lymphomas, and the other half are adenocarcinomas. The incidence of carcinoma of the small intestine in these patients is about 100-fold greater than that in the general population. Any patient with celiac sprue who becomes inexplicably refractory to gluten exclusion should be evaluated for a possible small intestine malignant disorder. Dermatitis Herpetiformis and Celiac Sprue Dermatitis herpetiformis usually occurs in association with celiac sprue. The vast majority of patients who have dermatitis herpetiformis can be shown to have flat jejunal villi, but less than five percent of these patients show the other typical signs of celiac sprue. (ref 39) The skin lesions of dermatitis herpetiformis are intensely pruritic blisters that appear on the shoulders, buttocks, knees, and elbows. Skin biopsy reveals immunoglobulin A (IgA) deposits in the involved lesions. A gluten-free diet may lessen the severity of the skin lesions in some patients. (ref 39) Skin lesions respond dramatically to therapy with dapsone but commonly recur if drug therapy is not maintained. The intestinal lesion does not appear to respond to dapsone but usually improves when gluten is eliminated from the diet. Therefore, it is assumed that most patients with dermatitis herpetiformis have the celiac sprue syndrome. Tropical Sprue Individuals living in tropical regions, including India, Puerto Rico, and Vietnam, appear to be at risk for tropical sprue, which consists of partial flattening of intestinal villi [see Figure 4] and subepithelial lymphocytic infiltration and is associated with malabsorption, weight loss, severe fatigue, and marked megaloblastic anemia. (ref 40) Anorexia is usually more severe than in celiac sprue and may be even more important than malabsorption in causing rapid weight loss. (ref 41) Tropical sprue appears to be linked to infection with an undefined agent. The syndrome develops in 10 percent of United States Army recruits stationed in Puerto Rico. Clinical symptoms may not be manifest in some cases until several months after the individual has returned from an endemic area. Seventy-five percent of patients respond within two weeks to folic acid therapy (5 mg p.o., t.i.d., for one week, followed by a maintenance dosage of 1 mg t.i.d). Both the anemia and the small intestine malabsorption are ameliorated by this therapy. One quarter of patients with tropical sprue, however, require antibiotic therapy (tetracycline, 500 mg q.i.d., or ampicillin, 500 mg q.i.d., for two to four weeks or longer) to achieve a remission. Several features of tropical sprue distinguish it from celiac sprue: the histologic appearance of the intestinal lesion, the exposure of patients to certain geographic locations, the severity of the megaloblastic anemia (hematocrits of 20 to 25 are not uncommon in tropical sprue), and the dramatic response to folic acid or antibiotics, which are not effective in celiac sprue.