Factitious diarrhea masquerading as refractory celiac disease.

Abstract: A 23-year-old female with a history of a histologically confirmed diagnosis of celiac disease was referred to our institution for refractory celiac disease for consideration of immunosuppressive therapy. Full workup revealed an elevated fecal magnesium level, and a concurrent diagnosis of laxative abuse was confirmed after discussion with the family. This case highlights the importance of considering factitious diarrhea in all patients admitted for refractory diarrhea, even those with documented underlying conditions.

Key Words: celiac disease, refractory celiac disease, factitious diarrhea, magnesium, laxatives

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Refractory diarrhea requiring hospitalization is a challenging clinical scenario for both the physician and the patient. We present a patient with a documented prior history of celiac disease admitted with refractory diarrhea that was factitious in etiology. This case illustrates the importance of maintaining a broad differential even in the patient carrying a prior diagnosis. Failure to do so may lead to unnecessary tests, expenses, and even iatrogenic harm.

Case Report

A 23-year-old female was transferred to our institution from an outside hospital with a diagnosis of refractory celiac disease. Two years prior, at the age of 21, she presented to her gastroenterologist with a chief complaint of abdominal discomfort and diarrhea. Workup at the time included flexible sigmoidoscopy with random biopsies, both of which were normal. Subsequent upper endoscopy with small bowel biopsies established a diagnosis of celiac disease. She was started on a strict gluten-free diet and her symptoms resolved entirely.

At the age of 22, the patient moved out of her parents' house. She resumed consuming gluten and redeveloped symptoms. Several months later, she presented to her gastroenterologist, now reporting approximately twenty watery bowel movements daily. After extensive discussions, she agreed to resume a gluten-free diet. However, her symptoms did not resolve. Subsequently, her local gastroenterologist prescribed a short course of oral steroids, which did not alleviate her symptoms. Due to ongoing diarrhea, evidence of hypovolemia, and hypokalemia, she was hospitalized for further evaluation.

Upper endoscopy was repeated upon admission. Some scalloping was noted visually and duodenal biopsies revealed crypt hyperplasia, intraepithelial lymphocytes, and villous blunting. The diagnosis of refractory celiac disease was made. During hospital admission, she was maintained on a strict gluten-free diet and IV steroids were begun. After two weeks of treatment, she reported no improvement in symptoms and she was transferred to our institution for consideration of further immunosuppressive therapy.

Medical history was otherwise negative. She denied taking any medications including over-the-counter herbal supplements. Family history was negative for celiac disease or inflammatory bowel disease. She denied tobacco or alcohol use. On presentation, she reported that she had approximately twenty bowel movements per day associated with abdominal pain, without evidence of bleeding. She did note, however, that she was rarely woken up at night due to diarrhea. She was afebrile, normotensive and without tachycardia. Initial laboratory tests were notable for a white blood cell count of 11.8 cells/mcL and a hematocrit of 35.1. Hepatic function tests were normal including an albumin of 3.8 g/dL. A metabolic panel was also normal with a serum magnesium of 2.5 mg/dL. Outside hospital biopsy slides were reviewed and the initial diagnosis of celiac disease was confirmed. Due to continued symptoms, upper endoscopy was again repeated with small bowel biopsies. Biopsies demonstrated mild villous blunting without crypt hyperplasia or intraepithelial lymphocytes.

Given the concern that symptoms appeared to be disproportionate to the initial histologic findings, and that symptoms persisted despite subsequent endoscopic and histologic resolution, further workup was performed. Fecal electrolytes revealed a sodium of 50 mEq/kg (0-160 mEq/kg), potassium 5 mEq (0-200 mEq/kg), and magnesium 1,144 mEq/kg (0-200 mEq/kg). Repeat fecal electrolytes confirmed the elevated fecal magnesium level.

After discussing the test results with the patient, she again denied surreptitious laxative use. However, when discussed in the presence of the patient's family, the mother reported finding a receipt for two 26-ounce bottles of milk of magnesia bought on the day the patient was admitted for dehydration. This prompted the patient to admit to using magnesium-containing laxatives. Following this discussion, her diarrhea quickly resolved and her steroids were tapered. The patient agreed to undergo counseling. With avoidance of gluten and laxatives, the patient continued to be symptom free 6 months later.

Discussion

Celiac disease is a genetically determined disease resulting in intolerance to gluten. (1) Wheat, rye, or barley exposure results in inflammation of the small bowel mucosa characterized on biopsy as villous blunting, crypt hyperplasia, and intraepithelial lymphocytosis. (2) The most common symptom at presentation is diarrhea, although patients may present with fatigue, vague abdominal discomfort, iron deficiency, or other nongastrointestinal symptoms. Although laboratory tests such as IgA tissue transglutaminase and endomysial antibody levels have a high sensitivity and specificity for celiac disease, the diagnosis should be confirmed with small bowel biopsies, as the diagnosis has lifelong implications. Prevalence in the United States and Europe is estimated at 1:250. (1)

Most patients readily respond to the cessation of all gluten in their diet, although strict adherence can be difficult, especially for younger patients. Refractory celiac disease is uncommon and in fact, most patients thought to have refractory celiac disease likely are consuming small amounts of gluten. (3) In rare cases, patients who are fastidious about a gluten-free diet may continue to have symptoms, serologies, and small bowel biopsies suggestive of celiac disease. In these clinical and histologic nonresponders, refractory celiac disease is a diagnosis of exclusion. After gluten intake is excluded, an exhaustive search for other etiologies should be performed. Intestinal lymphoma, ulcerative jejunitis, and autoimmune enteropathy among other diseases may mimic celiac disease clinically and histologically. (4) Treatment of refractory sprue is limited to case reports, but generally includes immunosuppressive therapy.

Other patients may have histologic resolution but with persistent clinical symptoms. In these patients, alternate etiologies for diarrhea should be sought. Coexisting bacterial overgrowth, inflammatory bowel disease, and collagenous colitis have been previously reported in the literature. (4) To our knowledge, coexisting factitial diarrhea has not previously been reported in the literature.

Patients may be hospitalized for diarrheal illnesses because of electrolyte derangements or the need for IV fluids or medications. A subset of patients whose diarrhea persists despite outpatient workup will also benefit from inpatient hospitalization so that diagnostic tests can be expedited and quantification of diarrhea (via 24-h stool weight) can be performed with accuracy. (5) Stool electrolytes and the calculation of osmotic gap allows the physician to determine whether the diarrhea is secretory or osmotic in nature and can thus help narrow the differential diagnosis (Table). (6) Fine and colleagues (7) defined a concentration of magnesium above 50 mMol as diarrheogenic. For pure magnesium-induced diarrhea (without additional laxatives such as phenolphthalein), the stool magnesium concentration is in excess of 100 mMol.

The diagnosis of factitious diarrhea is difficult for multiple reasons. Stool and urine analysis for laxatives is neither sensitive nor specific. The diagnosis is often one of exclusion after extensive workup as an inpatient. In addition, once the diagnosis is suspected, communication with the patient may become strained. The patient may become confrontational during questioning. Evidence supporting the diagnosis is thus helpful and some physicians advocate searching the patient's room for laxatives, although the ethics of this has been debated. (8) Despite these difficulties, it is important to consider factitious diarrhea in patients with refractory diarrhea.

Conclusion

This case highlights the importance of screening for potential laxative abuse in any patient with refractory diarrhea, even those with documented underlying conditions-Clues to the diagnosis in this case included serum magnesium level, elevated stool osmotic gap and persistent symptoms despite histologic resolution. This patient may have been otherwise subjected to potentially dangerous immunosuppressive therapy if this concurrent diagnosis was missed.

Acknowledgments

Carol E. Semrad, MD, David T. Rubin, MD, Beth Wall, MS, RD.

References

1. Green PH, Jabri B. Coeliac disease. Lancet 2003;362:383-391.

2. Trier J. Diagnosis of celiac sprue. Gastroenterology 1998;115:211-216.

3. Ciacci C, Mazzacca G. Unintentional gluten ingestion in celiac patients. Gastroenterology 1998;115:243.

4. Ryan BM, Kelleher D. Refractory celiac disease. Gastroenterology 2000;119:243-251.

5. Donowitz M, Kokke FT, Saidi R. Evaluation of patients with chronic diarrhea. N Engl J Med 1995;16:725-729.

6. Phillips S, Donaldson L, Geisler K. et al. Stool composition in factitial diarrhea: a 6-year experience with stool analysis. Ann Intern Med 1995;15:97-100.

7. Fine KD, Santa Ana CA, Fordtran JS. Diagnosis of magnesium-induced diarrhea. N Engl J Med 1991;324:1012-1017.

8. Plumeri PA. The room search. J Clin Gastroenterol 1984;6:181-185.</p> <pre> Nothing is a waste of time if you use the experience wisely. --Rodin </pre> <p>Rajesh N. Keswani, MD, Jenny Sauk, MD, and Sunanda V. Kane, MD

From the Section of Gastroenterology, University of Chicago Hospitals, and Department of Internal Medicine, University of Chicago Hospitals, Chicago, IL.

Reprint requests to Rajesh N. Keswani, MD, University of Chicago Hospitals, Section of Gastroenterology. Nutrition, and Hepatology, 5841 S. Maryland Avenue, MC 4076, Chicago, IL 60637. Email: [e-mail]

Accepted October 10, 2005.

RELATED ARTICLE: Key Points

* Celiac disease is a genetically determined disease that almost always readily responds to a gluten-free diet.

* Refractory celiac disease is an uncommon disease, and is one of exclusion.

* Diagnosis of factitious diarrhea requires a high index of suspicion and should be considered in all patients admitted for refractory diarrhea, even those with a documented underlying condition.

* Stool magnesium concentration can be very helpful in establishing a diagnosis of factitious diarrhea.

Table. Common causes of secretory and osmotic diarrhea

Secretory (> 125 mOsm/kg)   Osmotic (< 50 mOsm/kg)
Stimulant laxatives         Osmotic laxatives (Mg, P[O.sub.4],
                              S[O.sub.4])
Senna                       Magnesium citrate
Bisacodyl                   Milk of Magnesia
Phenolphthalein             Polyethylene glycol solution
Chronic alcohol ingestion   Magnesium-containing antacids
Bacterial infections        Carbohydrate malabsorption
Bile acid malabsorption     Lactase deficiency
Neoplasm                    Lactulose
Gastrinoma                  Sorbitol
VIPoma
Villous adenoma of rectum
Inflammatory Bowel Disease
Celiac disease
Hyperthyroidism