Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 5: Complaint-Specific Workups

Diarrhea

Background

Diarrhea is a common condition in HIV-infected individuals that may have a variety of causes. Episodes may be acute and brief, intermittent or recurrent, or, in some cases, chronic and severe. If diarrhea persists, it may cause poor nutrition, dehydration, and weight loss. Diarrhea may diminish patients' quality of life significantly, and may interfere with adherence to and efficacy of antiretroviral (ARV) medications.

Diarrhea is defined in various ways, but commonly as more than 4 loose stools or watery stools per day for more than 3 days. Duration is classified as follows:

• Acute: <2 weeks
• Persistent: 2-4 weeks
• Chronic: >4 weeks

The causes of diarrhea, both infectious and noninfectious, found in HIV-positive individuals with normal or mildly depressed CD4 cell counts are likely to be similar to those in HIV-uninfected persons. Among the noninfectious causes of diarrhea, adverse effects of ARVs and other medications are particularly common. Persons with advanced immunodeficiency are more likely to have infections, including opportunistic infections, as the cause of diarrhea.

Infectious diarrhea typically involves either the small or the large intestine, and the patient's history often suggests the site of the problem. Infections of the small intestine commonly produce generalized abdominal cramps, large-volume diarrhea without blood, and possibly dehydration. Large-intestine infections (colitis) often produce lower abdominal pain, an unproductive urge to defecate, and frequent small-volume stools with blood and pus.

S: Subjective

The patient complains of diarrhea. Take a thorough history, including the following:

• Onset of diarrhea
• Frequency (times per day, last episode)
• Stool consistency (soft vs liquid)
• Stool color (gray, white, or greasy stools: possible cholelithiasis or pancreatitis; dark stools: possible gastrointestinal bleeding)
• Bloody stools (possibly caused by invasive organisms, inflammation, ischemia, or neoplasm)
• Rectal bleeding
• Nausea or vomiting (if beginning within several hours of ingesting food, possible gastroenteritis)
• Weight loss: quantify amount and time frame
• Abdominal pain or cramping, and location if present
• Fever
• Other associated symptoms
• Allergies (to foods or medications)
• Aggravating factors
• Alleviating factors
• Treatments tried
• Contact with others with similar symptoms
• Previous episodes of diarrhea
• History of cytomegalovirus (CMV), Mycobacterium avium complex (MAC), or other infections involving the gastrointestinal tract
• Family history of inflammatory bowel disease, celiac disease
• Oral-anal sexual contact (males and females)
• Receptive anal intercourse
• Exposure to unsafely prepared food (eg, raw, undercooked, spoiled), unpasteurized milk, or juices
• Exposure to possibly contaminated water (swimming in or drinking from well, lake, or stream)
• Exposure to non-toilet-trained infants and children (eg, daycare), pets, farm animals, reptiles
• Recent travel
• Antibiotic use or exposure in recent weeks or months
• ARV medications, especially ritonavir or nelfinavir; check relationship of diarrhea onset to initiation of ARVs
• Other current and recent medications, including supplements (prescribed or over-the-counter) and herbal preparations
• Dietary factors, especially "sugar-free" foods (containing nonabsorbable carbohydrates), fat substitutes, milk products, and shellfish, or heavy intake of fruits, fruit juices, or caffeine
• Alcohol and recreational drug use; withdrawal

O: Objective

Record vital signs, including temperature, orthostatic heart rate, blood pressure measurements, and weight. Compare these with recent or baseline values. Perform a thorough physical examination, including evaluation of the following:

• Hydration status (skin turgor, mucous membrane moistness)
• Nutritional status (body habitus, muscle mass, skin and hair integrity)
• Oropharynx (lesions, candidiasis, ulcerations, Kaposi sarcoma)
• Optic fundi (signs of CMV infection)
• Abdomen (distention, bowel sounds, tenderness, organomegaly, masses, adenopathy)
• Rectum (masses, tenderness, bloody stool)

Review recent CD4 cell counts. Low CD4 counts increase the risk of chronic or systemic illnesses and opportunistic infections.

A: Assessment

The differential diagnosis is broad, and includes the following infectious and noninfectious causes:

Infectious Causes

Acute diarrhea, any CD4 count

• Viruses (especially Norwalk virus)
• Viral hepatitis
• Herpes enteritis
• Clostridium difficile (suspect in patients who have recently been treated with antibiotics)
• Salmonella
• Shigella
• Campylobacter
• Escherichia coli O157:H7

Chronic diarrhea, any CD4 count

• C difficile (suspect in patients who have recently been treated with antibiotics)
• Giardia lamblia
• Entamoeba histolytica

Chronic diarrhea, CD4 count <300 cells/µL

• Microsporidia
• Cryptosporidia
• MAC (CD4 count <50 cells/µL)
• Isospora belli
• CMV (CD4 count <100 cells/µL)

Adapted from: Infectious Causes of Diarrhea in Patients with HIV, Table 8-8. In: Bartlett JG, Cheever LW, Johnson MP, et al, eds. A Guide to Primary Care of People with HIV/AIDS. Rockville, MD: U.S. Department of Health and Human Services, Health Resources and Services Administration; 2004.

Noninfectious Causes

• Medication adverse effects, common with many medications including some ARVs:
  • Protease inhibitors (especially ritonavir and nelfinavir)
  • Didanosine buffered tablets (no longer available in the United States)
• Irritable bowel syndrome
• Inflammatory bowel disease (ulcerative colitis, Crohn disease)
• Lymphoma
• Lactose intolerance
• Celiac disease
• Small-bowel overgrowth
• Pancreatic insufficiency
• Diverticulitis
• Fecal incontinence

P: Plan

Diagnostic Evaluation

For suspected infections, perform laboratory studies including complete blood count with differential, electrolyte measurements, and liver function tests. Check stool for white blood cells and blood. Perform stool studies as indicated by the patient's presentation (bacterial culture, ova and parasites, microsporidia, cryptosporidia, Giardia, C difficile toxin assay). Order additional studies as suggested by the history (eg, blood cultures, MAC cultures, hepatitis serologies, retinal examination for CMV).

If the patient is febrile, perform a complete fever workup as appropriate (see chapter Fever).

Check the CD4 cell count and HIV viral load, if not checked recently.

If stool study results are negative (ova and parasite negative in 3 successive samples) and the patient has severe symptoms, particularly in the case of advanced immunodeficiency, refer to a gastroenterologist for colonoscopy or flexible sigmoidoscopy with biopsy. Endoscopy is the best procedure to identify certain conditions, including CMV colitis, and inflammatory bowel disease. If all studies are negative and the diarrhea persists, repeat endoscopy in 6-8 weeks regardless of the level of immunodeficiency. Pathogens may be difficult to identify.

Treatment

Once a diagnosis is made, initiate appropriate treatment. In seriously ill patients, presumptive treatment may be started while diagnostic tests are pending. See the appropriate chapter in Section 6: Disease-Specific Treatment or relevant treatment guidelines. If the cause of the diarrhea cannot be identified, consult with an HIV expert or a gastroenterologist.

For moderate to severe diarrhea, including dysentery (bloody diarrhea), empiric treatment can be given pending stool study results or in settings with limited resources for workup. Use fluoroquinolones in a 3-day regimen, including ciprofloxacin 500 mg twice daily, norfloxacin 400 mg twice daily, or levofloxacin 500 mg once daily. Monitor effectiveness and adjust therapy according to the results of diagnostic studies and clinical response.

For patients whose diarrhea is suspected to be due to ARV agents or other medications, symptomatic treatment may be tried (see below). Diarrhea from protease inhibitors often decreases after a few weeks without treatment. If the diarrhea cannot be controlled, a change in ARV regimen should be considered.

Symptomatic treatments

• Antimotility agents such as loperamide (Imodium) in over-the-counter or prescription strengths and atropine/diphenoxylate (Lomotil) are useful for many patients. The suggested dosage is 2 tablets after each loose bowel movement, not to exceed 8 tablets per day. These agents should not be used if patients have bloody diarrhea or if C difficile is suspected.
• Pharmaconutritional approaches include the use of calcium supplementation (500 mg 2-3 times daily). Patients with diarrhea related to protease inhibitors may find that taking calcium with each dose can decrease or prevent diarrhea. Note that magnesium supplements may worsen diarrhea.
• Pancrelipase (eg, Cotazym, Creon, Ultrase) can be useful in managing chronic diarrhea due to malabsorption. The dosage is 2-3 caplets 3 times daily with meals, titrated downward according to response.
• Cholestyramine (Questran) or psyllium (Metamucil) may reduce diarrhea by slowing peristalsis and adding bulk to stools. Avoid administering cholestyramine with other medications because it may impair their absorption.
• A combination of these treatments may be needed to control chronic diarrhea and can be continued for patients after an infectious process has been ruled out.

Nutrition and hydration

Encourage frequent intake of soft, easily digested foods such as bananas, rice, wheat, potatoes, noodles, boiled vegetables, crackers, and soups. Encourage hydration with fruit drinks, tea, "flat" carbonated beverages, and water. Patients should avoid high-sugar drinks, caffeinated beverages, alcohol, high-fiber foods, greasy or spicy foods, and dairy products. Many patients may benefit from a trial of a lactose-free, low-fiber, or low-fat diet. Patients should use nutritional supplements as needed or as recommended by a dietitian. In case of chronic or severe diarrhea, or significant weight loss, refer to a dietitian for further recommendations.

Patients with severe diarrhea must maintain adequate hydration, by mouth if possible. In severe cases, intravenous administration of fluids may be necessary. Oral rehydration solutions include the World Health Organization formula, Pedialyte, Rehydralyte, Rice-Lyte, and Resol. Homemade alternatives include the following:

• Combine 1/2 teaspoon of salt, 1 teaspoon of baking soda, 8 teaspoons of sugar, and 8 ounces of orange juice; add water to make l liter and drink.
• Drink 1 glass containing 8 ounces of apple, orange, or other juice; 1/2 teaspoon of corn syrup or honey; and a pinch of salt; then drink 1 glass containing 8 ounces of water and 1/4 teaspoon of baking soda.
• Mix 1/2 cup of dry, precooked baby rice cereal with 2 cups of water (boil first in areas with poor water quality); add 1/4 teaspoon of salt and drink.

Patient Education

• Diarrhea can have many causes. Instruct patients to notify their health care providers if they develop new or worsening symptoms.
• Instruct patients to take their medications exactly as directed and to call their health care providers if they experience worsening diarrhea, or other symptoms such as fever, nausea, vomiting, or pain.
• Patients must stay nourished and well hydrated even if they are having diarrhea. Instruct patients to eat small, frequent meals and to avoid dairy products, greasy food, and high-fat meals.

References

• Bartlett JG, Cheever LW, Johnson MP, et al, eds. A Guide to Primary Care of People with HIV/AIDS. Rockville, MD: U.S. Department of Health and Human Services, Health Resources and Services Administration; 2004. Available online at hab.hrsa.gov/tools/primarycareguide.
• American Medical Association, American Nurses Association--American Nurses Foundation, Centers for Disease Control and Prevention, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Food Safety and Inspection Service, US Department of Agriculture. Diagnosis and Management of Foodborne Illnesses. MMWR 2004; 53(RR04);1-33. Available online at www.cdc.gov/mmwr/preview/mmwrhtml/rr5304a1.htm.
• Centers for Disease Control and Prevention, National Institutes of Health, Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Exposed and Infected Children: Recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. December 3, 2004. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&GuidelineID=14.
• Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001 Feb 1;32(3):331-51.
• Sanaka M, Soffer E. Acute Diarrhea. Cleveland, OH: The Cleveland Clinic; 2004. Available online at www.clevelandclinicmeded.com/diseasemanagement/gastro/diarrhea/diarrhea.htm.
• Scheidler MD, Giannella RA. Practical management of acute diarrhea. Hosp Pract (Minneap). 2001 Jul 15;36(7):49-56.
• Thielman NM, Guerrant RL. An algorithmic approach to the workup and management of HIV-related diarrhea. J Clin Outcomes Management 1997;4:36-47.