Diarrhea (Case 24)
David Rudolph DO and James Thornton MD
Case: A 22-year-old man was referred to gastroenterology with intractable bloody diarrhea. His past medical history was unremarkable until last month, when he first noted the development of crampy abdominal pain, multiple daily bloody, mucus-filled stools, rectal urgency, and tenesmus. He also reported progressive fatigue, intermittent light-headedness, diminished appetite, and a subsequent 7-lb weight loss since symptom onset. He initially didn’t seek medical attention, because he thought the symptoms would just go away and, frankly, “just didn’t want to describe it to anyone.” He denied any recent travel, antibiotic use, close sick contacts, or high-risk sexual behaviors. On physical examination, he was somewhat ill-appearing with conjunctival pallor. Left lower quadrant abdominal tenderness was elicited with deep palpation, but no rebound or guarding was detected. The remainder of his physical examination was unremarkable.
Differential Diagnosis
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Infectious diarrhea |
Inflammatory bowel disease (IBD) |
IBS, functional diarrhea |
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Malabsorption |
Ischemic colitis |
Speaking Intelligently
When we encounter a patient with diarrhea, our investigation always begins with a thorough history and physical examination. The differential diagnosis for diarrhea is extremely broad, but by asking appropriate questions we can usually narrow the differential considerably. In addition, a complete physical examination helps differentiate which patients are currently stable and which patients are in need of more urgent medical attention. Volume depletion, a common sequela of secretory diarrhea, will be manifested by dry mucous membranes, poor skin turgor, and, if severe, tachycardia and hypotension. Anemia, a potential consequence of inflammatory diarrhea, should be suspected in the patient with diffuse pallor, fatigue, light-headedness, and exertional dyspnea.
PATIENT CARE
Clinical Thinking
• Pus or blood in the stools should alert the clinician to an invasive infectious or inflammatory etiology, which necessitates further workup. In this instance, initial evaluation should include checking stools for routine culture, leukocytes, and occult blood and, in the appropriate clinical setting, performing a Clostridium difficile assay and examination for ova and parasites.
History
Physical Examination
• Oral aphthous ulcers or episcleritis may be seen in patients with IBD.
• Perianal fissures, fistulas, or abscesses provide support for a diagnosis of Crohn disease.
• Palpable mass on DRE should raise suspicion for rectal neoplasm or fecal impaction.
Tests for Consideration
| Clinical Entities | Medical Knowledge |
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Infectious Diarrhea |
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Pφ |
Infectious diarrhea can be caused by viral, bacterial, fungal, or protozoal organisms. Most cases of acute infectious diarrhea are secondary to viruses, commonly rotavirus and noroviruses. The most common bacteria isolated include Campylobacter, Salmonella, Shigella, and Escherichia coli 0157:H7. Protozoal organisms, such as Giardia lamblia, Entamoeba histolytica, Cyclospora spp., Cryptosporidium, and Microsporidia spp., may be detected in patients who experience protracted diarrhea, especially after travel to endemic areas. Immunocompromised patients are at increased risk of infection by opportunistic pathogens including cytomegalovirus, Mycobacterium avium complex, Cryptosporidium, Isospora belli, and Microsporidium. |
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TP |
Patients with infectious diarrhea due to enterotoxin-producing organisms, such as Vibrio cholerae or enterotoxigenic E. coli, often present with voluminous watery diarrhea. These patients can develop severe volume depletion as evidenced by dry mucous membranes, poor skin turgor, tachycardia, and hypotension on examination. Infectious diarrhea due to invasive pathogens, such as Salmonella, Shigella, Campylobacter, C. difficile, and enterohemorrhagic E. coli, often results in dysentery. Systemic symptoms are more prevalent when diarrhea is secondary to invasive pathogens. |
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Acute infectious diarrhea is often self-limited. If the diarrhea is without blood or pus and the patient has no signs of systemic toxicity, additional evaluation is generally not warranted. Patients with bloody or mucus-filled diarrhea should have their stools checked for leukocytes (or lactoferrin) and bacterial culture. The need for additional testing should be based upon the patient’s clinical history. |
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Tx |
Initial management of patients with acute diarrhea should focus on fluid and electrolyte replacement. In most instances, antibiotic therapy is unnecessary. However, in patients with severe diarrhea, dysentery, or signs of systemic toxicity, empirical antibiotic therapy, often with a fluoroquinolone, should be considered. Antimicrobial therapy should be modified once the results of cultures are available. See Cecil Essentials 34, 103. |
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Inflammatory Bowel Disease |
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Pφ |
IBD generally refers to two idiopathic diseases, Crohn disease and ulcerative colitis, that cause chronic inflammation of the GI tract. While similar in many respects, the two diseases have distinct characteristics. Transmucosal inflammation is present in patients with Crohn disease, while inflammation from ulcerative colitis is confined to the mucosa and submucosa. Crohn disease can involve any portion of the GI tract, while ulcerative colitis is confined to the large bowel. Ulcerative colitis has nearly universal rectal involvement with continuous proximal expansion. Crohn disease often spares the rectum, and “skip lesions” can be detected indicating regions of uninvolved mucosa in between areas of active disease. |
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TP |
The typical patient with ulcerative colitis presents with bloody, mucus-filled diarrhea, crampy abdominal pain, rectal urgency, and tenesmus. Depending upon the severity of disease, patients may also present with fevers, decreased appetite, weight loss, and anemia. Patients with Crohn disease, like ulcerative colitis, also present with abdominal pain and diarrhea; however, bloody diarrhea is usually not as prominent in Crohn disease. Fissures, fistulas, strictures, and abscesses are more commonly seen in patients with Crohn disease, and patients often present with symptoms related to these complications. Extraintestinal manifestations, such as aphthous ulcers, erythema nodosum, pyoderma gangrenosum, episcleritis, uveitis, and primary sclerosing cholangitis may be present with both diseases. |
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Endoscopic evaluation with intestinal biopsies is necessary to confirm the diagnosis of IBD. In most instances, colonoscopy with intubation of the terminal ileum should be pursued. Stool cultures should also be obtained to exclude an infectious etiology. |
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Tx |
Treatment of Crohn disease and ulcerative colitis is similar and predicated on disease severity. Mild disease is often treated with 5-aminosalicylates. Antibiotic therapy may also be instituted for patients with Crohn disease with perianal involvement. Moderate disease often necessitates short-term corticosteroid therapy followed by maintenance therapy with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate). Severe disease is often managed with anti–tumor necrosis factor-α drugs (infliximab, adalimumab, certolizumab). Surgery is indicated for disease refractory to medical management and for complications of the disease such as perforation and obstruction. See Cecil Essentials 34, 38. |
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Irritable Bowel Syndrome, Functional Diarrhea |
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Pφ |
IBS is a functional disorder characterized by abdominal pain or cramping and altered bowel habits, either diarrhea or constipation, in the absence of discernible bowel pathology. The etiology remains unknown, but both hereditary and environmental factors are believed to have a role. Proposed risk factors for the development of IBS include previous GI infection, young age, female gender, anxiety, depression, and a family history of IBS. Upon questioning, patients with IBS often relate a history of anxiety, depression, or other psychological disorder. |
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TP |
Patients with IBS complain of abdominal pain or cramping along with altered frequency and consistency of stools. Bloating sensation, flatulence, nausea, and heartburn are also common complaints. Temporary relief of symptoms with defecation is a hallmark of IBS. |
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Dx |
Rome III criteria are widely used to identify patients with IBS. Recurrent abdominal pain or discomfort must be present at least 3 days per month for the last 3 months with any two of the following: temporary relief of symptoms with defecation, onset of pain associated with a change in the appearance of stools, onset of pain associated with a change in the frequency of stools. |
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Patients should be instructed to avoid foods that can trigger or exacerbate their symptoms. Fiber supplementation is generally recommended but should be used with caution initially, as patients can experience exacerbation of symptoms. Adjunctive therapy for treatment of IBS includes antispasmodics, antidiarrheal agents, antidepressants, and psychotherapy. See Cecil Essentials 34. |
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Malabsorption |
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Pφ |
Malabsorption refers to the impaired digestion or uptake of nutrients including carbohydrates, protein, fat, vitamins, and minerals. Malabsorption can occur as a result of inadequate intraluminal digestion, defective transport across the small intestinal mucosa, or impaired postabsorptive transport of nutrients into the circulation. Lactose intolerance, the most common form of carbohydrate malabsorption, results from an inherited or acquired deficiency of lactase. Fat malabsorption may result from celiac disease, short-bowel syndrome, postresection diarrhea, small-bowel bacterial overgrowth, mesenteric ischemia, pancreatic exocrine insufficiency, or inadequate luminal bile acid concentration. |
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TP |
Patients with global malabsorption will often present with diarrhea associated with weight loss, anorexia, and fatigue. Patients with lactose intolerance often present with crampy abdominal pain, bloating, flatulence, nausea, and watery diarrhea with symptom manifestation soon after ingestion of foods containing lactose. Patients with fat malabsorption report the passage of oily, foul-smelling stools that float, also known as steatorrhea. Malabsorption of fat-soluble vitamins may result in night blindness (vitamin A), osteopenia or osteomalacia (vitamin D), and bleeding (vitamin K). Iron deficiency anemia is commonly seen in patients with celiac disease. Peripheral edema and ascites may be a manifestation of protein malabsorption with resultant hypoalbuminemia. |
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Dx |
The gold standard for diagnosis of fat malabsorption is a 72-hour quantitative measurement of fecal fat. Alternatively, qualitative testing of stool with Sudan stain can be performed if quantitative testing is deemed too burdensome. Lactose intolerance can be assessed with a hydrogen breath test, with high levels of expelled hydrogen suggestive of carbohydrate malabsorption. Malabsorption from celiac disease, Whipple disease, Crohn disease, amyloidosis, or lymphoma can be established with upper endoscopy and small-bowel mucosal biopsies. Pancreatic exocrine insufficiency should be considered in patients with fat malabsorption and histologically normal small-bowel mucosa. |
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Celiac disease is treated with a gluten-free diet. Lactose intolerance is treated with avoidance of lactose-containing foods or with the ingestion of capsules containing lactase enzyme before meals. Fat malabsorption due to pancreatic exocrine insufficiency can be treated with ingestion of pancreatic enzyme supplements before meals. See Cecil Essentials 34, 38, 40. |
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Ischemic Colitis |
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Pφ |
Ischemic colitis results from the sudden loss, or reduction, of blood flow to the colon. Common etiologies of colonic ischemia include decreased perfusion (acute MI, congestive heart failure, cardiac arrhythmias, sepsis), vascular occlusion (secondary to thromboembolism), acute vasospasm, medications (cocaine, digoxin, alosetron, estrogens), vasculitis, and hypercoagulable states. |
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TP |
The typical presentation of ischemic colitis is an elderly patient with a history significant for cardiac or peripheral vascular disease who develops acute, often left-sided, abdominal pain followed shortly thereafter by the passage of bloody stools. Fever, nausea, and vomiting may also be present. |
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Dx |
Laboratory studies, while nondiagnostic, may reveal a leukocytosis and increased lactate; metabolic acidosis may also be present. Segmental bowel wall thickening will often be seen on radiographic imaging, but this finding is nonspecific, as it can also be seen in infectious colitis, IBD, and radiation colitis. Angiography is usually not indicated, as thromboembolic disease is rarely believed to be the cause of acute colonic ischemia. Definitive diagnosis is made with colonoscopy, which, depending upon the severity of inflammation, will often demonstrate inflamed mucosa, petechial hemorrhages, and, in severe cases, hemorrhagic ulcerations. |
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Tx |
Management of ischemic colitis is generally supportive. Intravenous fluids should be administered to maintain appropriate hydration. Patients should initially be kept on a regimen of nothing by mouth to allow for bowel rest. Antimicrobial therapy is recommended for moderate to severe cases. Surgery, while uncommon, is necessitated when there is evidence of bowel necrosis, gangrene, or perforation. See Cecil Essentials 34. |
Practice-Based Learning and Improvement: Evidence-Based Medicine
Title
Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial
Authors
Hanauer SB, Feagan BG, Lichtenstein GR, et al.; ACCENT I Study Group
Institution
Department of Gastroenterology and Nutrition, University of Chicago Medical Center
Reference
Lancet 2002; 359:1541–1549
Problem
Does maintenance infliximab therapy confer benefit in patients with active Crohn disease who respond to a single infusion of infliximab?
Intervention
Patients with moderately to severely active Crohn disease who responded favorably to an initial infusion of infliximab were randomized to one of three maintenance treatment groups: group 1: placebo at weeks 2 and 6, and then placebo every 8 weeks; group 2: infliximab 5 mg/kg at weeks 2 and 6, and then 5 mg/kg every 8 weeks; group 3: infliximab 5 mg/kg at weeks 2 and 6, and then 10 mg/kg every 8 weeks
Outcome/effect
Patients with Crohn disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54, to discontinue corticosteroids, and to maintain their response for a longer period of time, if infliximab treatment is maintained every 8 weeks.
Historical significance/comments
The results of the ACCENT I trial led to US Food and Drug Administration approval of infliximab as maintenance therapy for patients with moderately to severely active Crohn disease.
Interpersonal and Communication Skills
Have a Low Threshold to Screening for Abuse
When taking a medical history from a patient with a history of multiple GI complaints over a long period of time and no clearly established diagnosis, it becomes important to consider a psychosocial etiology for the patient’s symptoms. This is particularly true in patients with prolonged GI, genitourinary, or gynecologic complaints where an exhaustive workup has been negative. Often, these symptoms are manifestations of physical, sexual, or emotional abuse, and physicians need to elicit this history to recommend effective interventions. Asking patients if they “feel safe in their home” or if there has “ever been a time where they have not felt safe at home” is a good place to start. Even if the patient is not initially forthcoming, you may have effectively opened the door for future conversations. Establishing an environment of safety, confidentiality, and support is paramount. When appropriate, use this as an opportunity to include other members of the interdisciplinary team (e.g., social worker, counselor, or even a psychiatrist) to assist in the patient’s care.
Professionalism
Show Commitment to Professional Competence Informed by Medical Evidence
As C. difficile infection has become a prominent cause of diarrhea in both the outpatient and hospital setting, physicians have begun to recognize the increase in morbidity and mortality from antibiotic-associated diarrhea, particularly in older patients with significant comorbid conditions. The indiscriminate use of antibiotics has a prominent role in the high prevalence of this disease. Recognize that patients often feel the need to initiate therapy for treatment of nonspecific upper respiratory or genitourinary symptoms even when antibiotics are not clinically indicated. Not uncommonly, patients will “self-medicate” without first seeking the counsel of their primary-care physician. It is important for clinicians to take the time necessary to convey to patients that antibiotics are not innocuous medications and that they can, in fact, lead to the development of other disease states, such as C. difficile infection.
Understand Costs: Activity-Based Cost Accounting
You are sitting in the medical staff lounge and one of the gastroenterologists is complaining that he can no longer afford to perform endoscopies on patients with coverage from a certain insurance company because he doesn’t receive what it costs to provide care. Activity-based cost accounting may serve to clarify direct and indirect costs associated with provision of a service. In activity-based cost accounting, costs are assigned to the activities related to providing specific services. Direct costs are those associated with each office visit such as administrative costs of verifying insurance, communicating with referring physicians, and making the appointment. Indirect costs are those that occur throughout the year and must be allocated by procedure (e.g., rent, utilities, and office supplies). Identifying actual costs related to a visit improves your understanding of cost and revenue drivers. This information will serve you well in negotiating with managed-care organizations and analyzing changes in payment schedules. Your fluency with cost and revenue drivers allows you to review your system for cost-effectiveness.
