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Pediatric Lymphocytic Colitis Presenting With Intractable Diarrhea

Kuhn, Benjamin R.; Mezoff, Adam G.

Journal of Pediatric Gastroenterology and Nutrition: November 2011 - Volume 53 - Issue 5 - p 579–581
doi: 10.1097/MPG.0b013e3182214ac6
Case Reports
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Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Address correspondence and reprint requests to Benjamin R. Kuhn, DO, Cincinnati Children's Hospital Medical Center, Gastroenterology, Hepatology, & Nutrition, 3333 Burnet Ave, MLC 2010, Cincinnati, OH 45229-3039 (e-mail: benkuhn@hotmail.com).

Received 21 February, 2011

Accepted 5 April, 2011

The authors report no conflicts of interest.

Voluminous watery, nonbloody diarrhea is the hallmark of secretory diarrhea. The most common etiologies in children are infectious enterotoxins (cholera or an Escherichia coli) or vasoactive peptides such as vasoactive intestinal peptide (VIP). Stool output is excessive (>200 mL/kg) and does not respond to fasting. Lymphocytic colitis (LC) typically presents as watery diarrhea in adults, with rare reports in children (1,2). We describe the presentation, evaluation, and final diagnosis of an 8-year-old patient with profound watery diarrhea, ultimately diagnosed as having LC.

An 8-year-old previously healthy white boy presented to the emergency department after a syncopal episode while at school. He had several weeks of nonbloody, watery diarrhea 8 to 10 times per 24 hours, including at night, and a 7-pound weight loss. He had no abdominal pain, vomiting, or change in appetite. He was not taking medication or herbal supplementation at this time.

In the emergency department, an electrocardiogram demonstrated bigeminy and a prolonged QT, likely secondary to the electrolyte disturbance, including a potassium level of 1.1 mmol/L (Table 1). On physical examination the patient was interactive, although fatigued. He had dry mucous membranes and an irregular pulse. His abdomen was soft, nontender, and nondistended with normal bowel sounds. His perianal and digital rectal examinations were normal and hemoccult was negative. Height, weight, and body mass index were below the 3rd percentile.

TABLE 1

TABLE 1

After aggressive fluid and electrolyte repletion in the pediatric intensive care unit, the patient's cardiac dysrhythmia resolved and QT interval normalized. Cardiac enzymes peaked at 48 hours, including a troponin-I 2.12 ng/mL (normal range ≤0.4 ng/mL) and creatine kinase-MB 148 ng/mL (normal range ≤9.9 ng/mL). He had evidence of rhabdomyolysis with a creatine phosphokinase >24,000 U/L (normal range 75–215 U/L) and a large volume of blood detected on urinalysis, but <2 red blood cells per high-power field on spun urine microscopy (normal range <2 red blood cells/high-power field). This resolved as well.

During the patient's stabilization period, he was strictly nil per os and started on total parenteral nutrition. His stool output significantly reduced from 10 L/day on admission to 2 L on discharge 1 month later. Several endoscopies demonstrated pancolonic intraepithelial lymphocytosis of >20 lymphocytes per 100 enterocytes without cryptitis or granulomas (Fig. 1). Extensive evaluation was otherwise unrevealing (Table 2).

FIGURE 1

FIGURE 1

TABLE 2

TABLE 2

Pharmacotherapy was tested during hospitalization. Our patient was separately given metronidazole, loperamide, subcutaneous octreotide, and methylprednisolone. A noticeable improvement was observed with methylprednisolone. With decreased stool output, our patient tolerated a clear-liquid diet and no more than 1400 kcal/day because his stool output increased significantly when he took more than 1400 kcal/day. Once fluid balance and electrolyte stability were accomplished, our patient was discharged home on overnight intravenous fluids via peripherally inserted central catheter line. This was necessary to achieve daily fluid balance while continuing 2 L of stool output. All of the electrolytes, liver enzymes, and hematologic indices normalized during hospitalization. He was discharged home on prednisone, lansoprazole, ergocalciferol, ferrous sulfate, ADEKs, and zinc chloride supplementation.

At his 6-month follow-up appointment, the patient was continuing to improve, yet on repeat esophagogastroduodenoscopy/colonoscopy, he was histologically unchanged. The home overnight intravenous fluids were discontinued, and his peripherally inserted central catheter line was removed. He was started on enteral budesonide. One year later, esophagogastroduodenoscopy/colonoscopy was visually and histologically normal.

After extensive investigation, our patient's unifying diagnosis remains LC confirmed by 3 endoscopies demonstrating pancolonic intraepithelial lymphocytosis with >20 lymphocytes per 100 enterocytes.

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DISCUSSION

Chronic diarrhea can be categorized as secretory, osmotic, or mixed. Patients with secretory diarrhea have significant ongoing losses despite nil per os status, and stool electrolytes show a stool sodium >70 mEq/L with a stool osmotic gap <50 mOsm/kg. Etiologies of secretory diarrhea in children include hormonal (neuroendocrine tumors, GIPoma, VIPoma), inflammatory, and mucosal. LC is associated with microscopic inflammatory infiltrates, but the primary pathophysiologic event is that of secretory diarrhea (2). Our patient had clear evidence of secretory diarrhea with massive fecal losses that did not respond to fasting. Although his stool electrolytes suggest somewhat of a mixed pattern of osmotic and secretory diarrhea, the primary pathophysiologic mechanism for his complaint was that of a secretory process.

LC is well described in adults, although rarely seen in children. Our patient's presenting symptoms were several weeks of intractable nonbloody diarrhea leading to severe hypokalemia and resulting in cardiac dysrhythmia, rhabdomyolysis, and a syncopal event. This is consistent with the spectrum of presenting symptoms in adults in addition to the histologic findings of increased intraepithelial lymphocytes present within the colonic mucosa (3). Other findings may include weight loss, abdominal pain, and electrolyte disturbances.

LC is diagnosed by colonoscopy with biopsies demonstrating >20 lymphocytes per 100 epithelial cells. Three adult LC incidence estimates are 3 to 5/100,000 per year, and affecting both sexes equally, with a mean age at diagnosis of approximately 65 years (4–7). The clinical course in adults is waxing and waning for several years, with 80% of patients showing clinical and histological resolution by 3 years (4).

LC is a condition included in the microscopic colitis family, which contains 2 subtypes, LC and collagenous colitis. The symptoms and clinical courses are similar; however, collagenous colitis demonstrates a thickened subepithelial collagen layer >10 μm (normal range 5–7 μm) within the lamina propria (8,9), which was not found in our patient.

The differential diagnosis of the clinical and histological findings in LC includes celiac sprue, Crohn disease, giardiasis, irritable bowel syndrome, ulcerative colitis, hyperthyroidism, infectious colitis, ischemic colitis, laxative abuse, and medications including selective serotonin inhibitors, ranitidine, aspirin, nonsteroidal anti-inflammatory drugs, acarbose, ticlopidine, and proton pump inhibitors. The most common cause, however, remains idiopathic.

Our patient's evaluation for celiac disease included normal serologic markers (Table 2) and normal histologic findings from duodenal and duodenal bulb biopsies demonstrating normal crypt-villous height ratio, lack of villous blunting, and no increase in intraepithelial lymphocytes in the duodenum.

Treatment modalities for LC include bismuth subsalicylate, budesonide, mesalamine, prednisolone, and probiotics (10–17). Fine et al (13) reported that bismuth subsalicylate treatment was ineffective for clinical or histologic response at 8 weeks versus placebo in a small number of patients (n = 5). Budesonide for 6 weeks is reported to show a clinical response (P = 0.004) and histological resolution (P = 0.04; n = 41; number needed to treat = 3 patients) (15). In a nonplacebo controlled trial of mesalamine versus mesalamine + cholestyramine, no significant difference was noted in clinical response (P = 0.95; n = 40), although the overall clinical response was 85% and 86%, respectively (12). Our patient was separately given metronidazole, loperamide, subcutaneous octreotide, and methylprednisolone, with improvement seen with corticosteroids.

The present case report of a child with chronic secretory diarrhea, profound electrolyte disturbance, and rhabdomyolysis joins a group of extremely rare cases of LC in the pediatric population. Management and outcomes are limited to adult data, making extrapolation to pediatrics difficult. Additional reports are needed to provide insight into diagnostic dilemmas, treatment, and outcomes for these critically ill children.

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