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A 21-year-old woman presented to the clinic with complaints of diarrhoea and abdominal bloating, particularly after meals. The symptoms had been present for months, and she had had minor weight loss (4 kg) during that time. She had been in good general health but had experienced food intolerance as a young child. The patient could not recall any details of that food intolerance but had not had problems since then. She denied travel and had not had any known exposure to well water. Pertinent details from the family history included irritable bowel syndrome (IBS) in a brother and "gluten intolerance" in an older sister. On examination, her vital signs were normal, her weight was 61 kg, and her height was 167 cm. She had no abdominal tenderness, palpable masses, nor organomegaly. She also had no skin rash, cheilitis, nor oral ulcers. Her rectum was non-tender on examination, her stool was not formed, and the result of a stool guaiac test was negative. Initial stool studies for ova and parasites and for clostridium toxin were negative. |
A patient with gastroenteritis might present with diarrhoea, but it is usually of short duration and does not lead to significant weight loss. Crohn’s disease usually is associated with abdominal tenderness and may also manifest with an abdominal mass, fever, oral or perianal ulcers, and extraintestinal symptoms such as joint swelling. Patients with ulcerative colitis often present with bloody diarrhoea and tenesmus. Fever, abdominal tenderness, and extraintestinal symptoms may be seen with ulcerative colitis, just as with Crohn’s disease. Patients with small bowel lymphoma can present with chronic diarrhoea with or without malabsorption. Coeliac sprue, lactose intolerance, and other food-intolerance syndromes may also cause chronic diarrhoea, though with the exception of coeliac sprue, they are not usually associated with malabsorption.
IBS can cause symptoms after meals, but they are usually not severe enough to cause weight loss, so IBS is not a likely cause of this patient’s symptoms. Malabsorption from gallbladder obstruction or pancreatitis would be associated with symptoms of those conditions (e.g. right upper quadrant pain with the former and marked mid-abdominal tenderness with the latter) and therefore are unlikely to explain her symptoms.
A few initial tests can be done before proceeding to endoscopy and biopsy. Some stool studies have already been done, but they may not be sensitive enough to detect amoebiasis. With her family history, it would be appropriate to initiate testing for coeliac sprue, noting that if testing is suggestive, upper endoscopy would be indicated to confirm this disease. If results are negative for coeliac sprue, colonoscopy for biopsy to evaluate for Crohn’s disease or ulcerative colitis would be indicated as well as further testing for amoebiasis.
Electrolyte imbalances may result from malabsorption, and therefore serum electrolyte levels should be evaluated. Other blood test abnormalities caused by malabsorption might include hypoproteinaemia, anaemia, hypokalaemia, and prolonged bleeding times, and these should be evaluated as part of the work-up if malabsorption is suspected.
The first test for coeliac sprue is serologic testing. Immunoglobulin A antihuman tissue transglutaminase and IgA endomysial antibody immunofluorescence tests have high sensitivity and specificity for coeliac sprue. The diagnostic accuracy is sufficient enough that these tests can also be used to monitor adherence to the diet, or for screening for patients with an unclear diagnosis for chronic diarrhoea. Elevated levels of IgA antibodies to the smooth muscle endomysium of the intestine are specific for coeliac sprue. Serum IgG and IgA gliadin antibodies offer 78% and 55% sensitivity for diagnosing coeliac sprue, respectively. The specificity for IgG to gliadin is 82%, but it is 100% for IgA to gliadin.
However, despite the accuracy of serologic testing, biopsy with histological diagnosis remains the gold standard for diagnosis. The presence of villus atrophy must be documented, whereas the presence of lymphocytic infiltrates and mucus cell crypt hyperplasia are later findings that may not be present initially. Multiple biopsy specimens must be taken, as the mucosa may be affected in a noncontiguous manner. Although routine endoscopy without a biopsy cannot conclusively lead to a diagnosis of coeliac sprue, endoscopy with an immersion technique, in which the inflated duodenal lumen is collapsed and then filled quickly with water, can demonstrate the presence or absence of villi. If villi are present, they raise up as they float into the water and become visible. Otherwise, in the insufflated bowel, they are flattened down and not visible. In addition, high-magnification scopes are now available, which help directly visualize the mucosa to determine whether villi are present. In trained hands, these tests approach 100% sensitivity and specificity, potentially obviating the need for biopsy.
Coeliac sprue, also known as gluten-sensitive enteropathy, is a chronic autoimmune enteropathy characterized by an inflammatory response in the intestinal mucosa caused by ingestion of gliadin, an alcohol-soluble protein in wheat. Gluten is the protein in wheat, rye, and barley that can be fractionated into ethanol-soluble gliadins and other proteins. The inflammatory response to gliadin appears to be immunologically mediated by helper T cells, and the result is impaired digestion and malabsorption. The presence of antibodies to the smooth muscle endomysium suggests an autoimmune process.
Pathophysiologically, lymphocytic infiltration of the epithelium develops. The intestinal mucosa loses the intestinal villi, and the intestinal crypts are lengthened. The loss of villi leads to the malabsorptive symptoms of the disease. The mucosa is primarily involved, and the submucosa and deeper tissues are not affected.
The most common symptoms of coeliac sprue are the result of malabsorption, and they include chronic diarrhoea, steatorrhoea, weight loss, flatulence, bloating, and abdominal cramping. In addition, malabsorption can lead to anaemia caused by poor iron and folate absorption in the proximal small bowel, osteopenia caused by decreased vitamin D and calcium absorption, and prolonged bleeding times caused by impaired vitamin K absorption. Seizures can occur if severe hypocalcaemia is present. Dermatitis herpetiformis may develop.
Patients are typically about 8 to 12 months of age when symptoms of the disease initially occur, correlating with the first consumption of foods containing gluten. An increase in incidence also occurs among persons aged 20 to 30 years.
On examination, a patient may have abdominal distention. Other physical abnormalities that might be present are the result of malabsorption: weight loss, muscle wasting, signs of anaemia, bleeding (e.g. gums bleeding, ecchymoses), peripheral neuropathy, and skin abnormalities.
Despite the classic presentation for many patients as described, most patients are asymptomatic and may remain so until an environmental trigger occurs. This appears to be the case for persons who undergo a period of decreased or absent symptoms during adolescence. Up to 50% of persons may be asymptomatic.
Dermatitis herpetiformis, a pruritic papulovesicular rash may be present with characteristic involvement of the elbows, knees, buttocks, and scalp. On histological examination, IgA is present in the dermal papillary tips. Alopecia areata, psoriasis, and stomatitis are other dermatological manifestations of coeliac sprue.
The primary treatment for coeliac sprue is dietary avoidance (absolute) of gluten. Even small amounts of gluten can cause the symptoms to persist. Patients are considered refractory to treatment if the symptoms persist despite a full 6 months of full compliance with a gluten-free diet. In some patients with refractory disease, treatment with systemic glucocorticoids may be necessary to control the symptoms. Reports exist of patients who have responded to treatment with immunomodulating drugs, namely infliximab and azathioprine.
A gluten-free diet is difficult to maintain, so it is important that the patient work with a dietician to learn how to manage the diet. All products that contain wheat flour, rye, and barley also contain gluten. In addition, the proteins in oats are related to wheat proteins, so patients are advised not to eat oats.
Most patients who maintain a gluten-free diet do very well. A small group of patients do not respond to dietary restriction alone, and these persons are difficult to treat. In general, long-term treatment with corticosteroids is necessary in these patients.