Celiac Disease an Underrecognized Cause of Chronic Diarrhea

Resident & Staff Physician®November 2005
Volume 0
Issue 0

Dennis Borna, MD

Steven Glass, MD

Family Medicine Residency Program

Fontana, Calif

Case Presentation

A 62-year-old white woman came to an urgent care clinic complaining of 2 weeks'duration of intractable diarrhea, abdominal pain, and a general feeling of profound weakness. She denied vomiting, fever, bloody stools, melena, or travel history. Upon further questioning, the patient admitted having loose stools off and on for several years, adding that over the past few months it was occurring more frequently. She was particularly alarmed that she was having up to 10 episodes of loose, watery stools daily for the past 2 weeks. She said she had lost 10 to 20 lb over the past 2 to 3 years. Her medical history was significant for hypothyroidism, depression, and emphysema. Her medications included levothyroxine sodium (eg, Levoxyl, Synthroid, Thyro-Tabs); fluoxetine HCl (Prozac); and inhaled albuterol (AccuNeb, Proventil), salmeterol xinafoate (Serevent Diskus), and ipratropium bromide (Atrovent). She had a hysterectomy 20 years ago because of fibroids.

Physical examination showed she was afebrile, with a blood pressure of 95/68 mm Hg and a pulse rate of 72 beats/min. Her abdomen had mild, diffuse tenderness to palpation throughout but was nondistended, with normal bowel sounds and no other significant findings. She was sent to have a computed tomography (CT) scan of the abdomen but collapsed on the way to the scanner. After receiving 1 L of normal saline intravenously, she felt a little better, but was still unsteady and was admitted to the hospital.

Additional testing included an electrolyte panel, which was notable for a slightly elevated blood urea nitrogen level of 10.7 mmol/L (serum creatinine, 53.0 ?mol/L), suggesting mild dehydration. Complete blood cell (CBC) count revealed she was anemic (hemoglobin, 90 g/L). The thyroid panel was within normal limits. Stool studies ruled out occult blood and infectious organisms. The iron panel was significantly low: serum iron concentration, 3.0 ?mol/L; total iron-binding capacity, 31.5 ?mol/L. Ferritin was normal (85 ?g/L).

A subsequent abdominal CT scan was unremarkable. A small bowel series showed some mucosal thickening of the duodenum and jejunum. Because she continued to have frequent loose stools in the hospital, a gastroenterologist was consulted. Endoscopy with possible biopsy was the next necessary step. Sigmoidoscopy was unremarkable, but upper endoscopy revealed an atrophic duodenum consistent with celiac sprue. A duodenal biopsy showed flattened villi with crypt elongation and hyperplasia along with infiltration of lymphocytes, confirming the diagnosis of celiac disease. Tests of a serum sample obtained earlier in the hospital were positive for antigliadin immunoglobulin (Ig)A and IgG antibodies, and for antiendomysial antibodies.

After the patient was switched to a gluten-free diet, she noticed an almost immediate improvement. She was discharged, and at follow-up in the clinic 2 weeks later she was completely symptom free. A CBC count 2 months later showed that she was no longer anemic, and she had regained 10 lb. She has since continued her gluten-free diet and is doing well.


Diarrhea can have a number of causes, ranging from infectious to inflammatory. One cause that is often overlooked is celiac disease, which frequently produces a spectrum of problems, often in the setting of malabsorption. Celiac disease is an enteropathy wherein the ingestion of wheat-derived gluten in susceptible individuals sets off a T-lymphocyte-mediated inflammatory cascade in the proximal small intestine (Figure 1). This inflammation results in an inability to absorb vitamins and minerals as well as proteins, carbohydrates, and fats. The resultant malabsorptive state leads to a number of clinical problems.

As we learn more about celiac disease, we are becoming better equipped to diagnose it. It is necessary to have an index of suspicion in patients with typical presenting signs and symptoms, and in those at increased risk, so that the correct tests can be ordered that will ultimately lead the physician to biopsy. Once properly diagnosed, patients with celiac disease do quite well with dietary modifications, and the ultimate long-term ill effects can be avoided.


Once thought to occur in only 1 in 1000 individuals, recent studies suggest that the actual prevalence of celiac disease in the United States ranges from 1:22 in first-degree relatives of patients with biopsy-proven celiac disease to 1:133 in persons who have no risk factors for the disease.1 This higher prevalence probably reflects our improved ability to detect the disease since our knowledge base has grown. Women make up about 75% of all patients.2 Celiac disease is virtually nonexistent among blacks and Asians.3 In a study of 3654 Finnish children aged 7 to 16 years, 1 in 67 had HLAtypes and serum markers compatible with sprue and 1 in 99 had biopsy-proven celiac disease.4

The etiology of celiac disease is not fully understood, but it is considered an autoimmune condition. A group of HLA genes is associated with celiac disease; specific haplotypes are expressed in almost all patients. In addition, the presence of tissue transglutaminase (tTG) antibodies plays a key role in the antigenicity of the ingested gluten.5 Both the wide variability of HLA haplotypes and the quantity of tTG antibodies result in a broad spectrum of disease. However, not all susceptible persons develop the disease. In patients who develop celiac disease later in life, some of the antibodies may not be detectable for several years.

Symptoms and signs

Patients can be asymptomatic or have major gastrointestinal (GI) complaints. Although the typical presenting symptoms are diarrhea and abdominal pain, nonspecific findings of gas, bloating, fatigue, and weight loss are also very common. In patients with relatively mild chronic symptoms, celiac disease can be mistaken for irritable bowel syndrome.

Common non-GI symptoms include bone pain, oral lesions (eg, glossitis, aphthous ulcers), anemia, dermatologic conditions, arthritis, alopecia areata, infertility, and dental enamel hypoplasia. Dermatitis herpetiformis, an intensely pruritic herpeticlike rash on the trunk, knees, or elbows, is seen in approximately 11% of patients with subclinical celiac disease.6

The underdiagnosis of celiac disease can have profound consequences, since lymphoma or GI carcinoma occurs in up to 15% of patients with untreated or refractory disease.3 Malignancy is particularly a concern in the elderly. In one study, the overall incidence of malignant lymphoma in all patients with celiac disease was 8.4%, compared with 22% when it was limited to elderly patients.7

Classically, celiac disease presents in infancy when wheat, barley, or rye cereals are introduced into the diet. Diarrhea and failure to thrive can occur months to years thereafter. The specific timing of the introduction of gluten during infancy may also play a role in the development of the disease.8 We now know that celiac disease can be essentially silent in some people, with abnormal antibodies the only sign. In others, celiac disease remains latent for years, followed by a gradual or late acute onset of GI symptoms.9 Up to 20% of patients are older than 60 years.10 There seems to be some association with other autoimmune disorders, including type 1 diabetes.11

Diagnostic tests and common findings

Typical laboratory findings in celiac disease are primarily the result of malabsorption. About half of all patients have anemia, largely because of the inability to absorb iron or folate. Chronic occult blood loss through the GI tract can also contribute to iron-deficiency anemia, although the prevalence of this is controversial.12,13 In addition to deficiencies of iron and folate, levels of calcium and serum 25-hydroxyvitamin D are also reduced, and are primary contributors to low bone density. All adults with celiac disease should undergo bone density scanning at the time of diagnosis.

Nonspecific findings of celiac disease are common and include thrombocytosis, mildly elevated liver function test values, and low phosphorus and elevated alkaline phosphatase levels. Low albumin concentration can be a clue to the severity of nutritional deficiencies. The presence of these abnormalities in a patient with GI and/or extraintestinal symptoms should prompt at least the consideration of celiac disease.

More specific tests include IgA antiendomysial antibodies, IgA and IgG antigliadin antibodies, and IgA anti-tTG antibodies (Table). These tests are generally more than 80% sensitive and specific.5 Although IgA antiendomysial antibodies are perhaps the most sensitive and specific serologic markers, tests for these are gradually being replaced with tests for IgA anti-tTG antibodies, which are more readily available and, with the relatively newly developed enzyme-linked immunosorbent assay based on the use of human recombinant enzyme, have similar sensitivities and specificities.14

The gold standard for the diagnosis of celiac disease is upper endoscopy with duodenal biopsy. Typical endoscopic findings are a loss of characteristic folds, with scalloping and a mosaic pattern on the mucosa (Figure 2). Histologic analysis reveals increased intraepithelial lymphocytes, with villous atrophy and crypt hyperplasia.15 Because of the relatively high cost and invasiveness of endoscopy with biopsy, and because the enzyme serology has such high sensitivity and specificity, it has been suggested that a thorough history combined with positive laboratory test results may obviate the need for endoscopy. There is, however, considerable opposition to this approach since symptoms can be vague, and switching to a gluten-free diet is an expensive and often difficult lifelong commitment. Many gastroenterologists, however, believe that a repeat endoscopic biopsy after initiation of treatment in patients with confirmed sprue is unnecessary and that reversion of IgA antiendomysial or anti-tTG antibodies to negative is sufficient confirmation of disease resolution.5


The treatment for celiac disease consists of restricting gluten from the diet. Gluten, the protein in wheat grain, is water insoluble. Although theoretically it is only contained in wheat products, some oat-containing products are also contaminated with the protein.16 Dietary consultation with a nutritionist is important for drawing up a suitable diet plan. Follow-up is recommended, with repeat measurements of CBC count, iron studies, total protein, chemistry panel, and vitamin B12 and folate levels, when any abnormalities in these values occur at the time of diagnosis. Persistent abnormalities warrant further workup.

Calcium supplementation, antiresorptive agents, and/or estrogen supplementation (in postmenopausal women) may be necessary for patients with significantly low bone mineral density at the time of diagnosis. The resolution of symptoms and the normalization of serum laboratory test results is the rule for the vast majority of patients after therapy.


The case presented here illustrates the importance of recognizing a disease that can easily be, and often is, overlooked as a cause of nonspecific GI and/or systemic symptoms. Diarrhea and abdominal pain occur in a wide variety of conditions. The prevalence of celiac disease is such that we can no longer discount it as an extremely rare zebra. Rather, it should be included in the differential diagnosis of patients with chronic signs and symptoms of malabsorption associated with problems such as anemia, elevated liver enzymes, or unexplained oral or dermatologic lesions. A high enough index of suspicion can lead to obtaining more specific laboratory tests. The test results and severity of the disease help determine the need for endoscopy and biopsy for definitive diagnosis. Unless their symptoms are severe, most individuals can be evaluated in the outpatient setting. Treatment is based on dietary modification, with the elimination of gluten from the diet. With good compliance, most patients enjoy a prompt return to health.

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7. Freeman JH. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease. 2004;38:429-434.


8. Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. 2005;293:2343-2351.


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13. Logan RF, Howarth GF, West J, et al. How often is a positive faecal occult blood test the result of coeliac disease? . 2003;15:1097-1100.

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An excellent resource for patient education is:

The Celiac Sprue Association Phone: (877) CSA-4-CSA

E-mail: celiacs@csaceliacs.org

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