Diarrhea in HIV-Infected Patients
Gastrointestinal disease is a major problem in patients with HIV and AIDS, and diarrhea is reported in up to 60% of patients with AIDS. Diarrhea may wax and wane over time, and in at least 30% of patients, an etiology cannot be determined. In such cases, the diarrhea is often attributed to HIV enteropathy.
I. Clinical Evaluation of AIDS-Associated Diarrhea
A. The history should include the duration of symptoms, frequency and characteristics of stools, and the CD4 count. The amount and rate of weight loss, residential exposures, occupational exposures, recent travel, pets, hobbies (ie, fishing, hunting, cooking), and type of water supply should be assessed.
B. Recent antibiotic or antiretroviral use, previous opportunistic infections, and other illnesses or hospitalizations should be assessed.
C. Sexually transmitted diseases, intake of unpasteurized dairy products, or raw or under-cooked meat or shellfish should be sought.
D. Small-bowel diarrhea is generally watery and occurs in large volume (up to 10,000 mL/day).
1. Abdominal cramping, bloating, gas, and profound weight loss may occur.
2. Fever is absent and stool examinations for occult blood and fecal leukocytes are negative.
E. Large-bowel Disease is characterized by frequent, regular, small-volume, often painful bowel movements. Fever and bloody or mucoid stools are common, and fecal leukocytes are positive.
F. Systemic Diseases, such as disseminated Mycobacterium avium infection, may present with diarrhea with persistent fever, severe weight loss, and symptomatic anemia.
CD4 Count as a Predictor of Pathogens Causing Diarrheal Disease
II. Physical Examination
A. Height and weight, temperature, orthostatic blood pressure, and degree of wasting are documented.
B. Dermatitis may suggest zinc deficiency and stomatitis may suggest vitamin B-12 deficiency.
C. CMV retinitis raises the possibility that gastrointestinal disease may also be caused by CMV.
D. Organomegaly may be the first sign of disseminated mycobacterial infection, histoplasmosis, or lymphoma.
E. Neurologic examination should include an assessment of long tract function (vibration and position sense) which may indicate vitamin B-12 deficiency.
III. Laboratory Evaluation of Diarrhea
A. Initial evaluation consists of stool cultures for enteric organisms, an assay for C. difficile toxin (not culture), fecal leukocyte count, and examination for ova and parasites.
B. Blood cultures for bacteria are appropriate in febrile patients.
C. In febrile patients with a CD4 cell count <200, two sets of blood cultures for mycobacteria or fungi should also be submitted.
D. Modified acid-fast smear for cryptosporidia is appropriate in patients with very low CD4 cell counts and severe diarrhea.
E. If the initial evaluation is negative, the studies should be repeated once or twice more in case a pathogen was missed. If these tests are negative and diarrhea persists, options include flexible sigmoidoscopy or colonoscopy and treating empirically with antidiarrheals.
IV. Symptomatic Treatment of Chronic Diarrhea
A. Loperamide (Imodium) 4 mg po initially, then 2 mg q6h around the clock and prn (maximum 16 mg qd).
B. Diphenoxylate-atropine (Lomotil) 2.5-5 mg po 3-6 times daily for 24-48 hr, then 2.5-5 mg tid and prn to control diarrhea (maximum 20 mg qd).
C. Paregoric 0.4 mg morphine/mL, 5-10 mL qd-qid.
V. Bacterial Small-bowel Pathogens
A. Salmonella
1. Salmonella can involve either the small or large bowel or both. It often causes watery, non-bloody, non-mucoid diarrhea typical of small-bowel disease. Fever is often present.
2. Salmonella infection can develop before and after the diagnosis of AIDS.
3. Blood cultures should be submitted when this diagnosis is suspected.
4. Relapses are common without maintenance therapy. Antibiotics active against Salmonella (ie, trimethoprim-sulfamethoxazole, fluoroquinolone) prevent relapse.
B. Mycobacteria
1. Mycobacterium avium complex and Mycobacterium tuberculosis both cause systemic infections in AIDS, although M. avium is much more commonly associated with diarrheal disease. MAC affects 25% of AIDS patients.
2. Disseminated M. avium infection generally occurs several months after the diagnosis of AIDS. CD4 counts are in the range of 60 cells/µL, and infection in those with counts >100 cells/µL is rare.
3. Malabsorptive diarrhea, persistent fever and weight loss are typical of small bowel involvement.
4. Focal lesions of the gastrointestinal tract often involve the duodenum, and organisms characteristically disseminate to bone-marrow, liver,spleen and lymph nodes.
5. Blood cultures are 98% sensitive if two samples are submitted. Neither a positive stool culture for MAC nor the presence of acid-fast organisms on smear is diagnostic; however, the smear is strongly suggestive of intestinal infection.
VI. Protozoa Small Bowel Pathogens
A. Cryptosporidium enteritis most often occurs in patients with AIDS, and it is the most common cause of diarrhea in this group (16%).
1. Small-bowel disease is characterized by large-volume non-bloody diarrhea, nausea, vomiting, abdominal pain, and weight loss. Gastric outlet obstruction, colitis and toxic megacolon may occur.
2. Cryptosporidia is one of the more common causes of chronic, seemingly pathogen-negative diarrhea.
3. CD4 counts >180 cells/µL are associated with spontaneous resolution of diarrhea within 1-4 weeks. However, counts <180 cells/µL are associated with persistent disease.
4. Modified Ziehl-Neelsen or immunofluorescence staining of a stool sample generally reveals the pathogen.
B. Microsporidia
1. This disorder is characterized by chronic, intermittent, watery, non-bloody diarrhea and weight loss without fever or abdominal pain.
2. Patients usually have CD4 values of <30-35 cells/µL. Therefore, the initial evaluation of diarrhea in HIV-infected patients with CD4 counts above 100 cells/µL need not include tests for Microsporidia.
3. Modified trichrome and chitin stains are diagnostic.
C. Isospora belli
1. Isospora belli causes a chronic diarrheal syndrome indistinguishable from that caused by Cryptosporidia.
2. Infection with this pathogen is rare in the United States, and those affected are primarily immigrants from Mexico, Latin and Central America.
3. Eosinophilia and an appropriate exposure history in an AIDS patient with diarrhea suggests I. belli.
VII. HIV Small Bowel Enteropathy
A. HIV itself may cause a “pathogen-free” chronic diarrhea in AIDS patients.
B. Some HIV-infected patients with relatively intact immune systems develop chronic diarrhea in the absence of identifiable pathogens.
C. A search for other pathogens should be completed before attributing diarrheal disease to HIV enteropathy.
VIII. Bacterial Large-bowel Pathogens
A. Shigella
1. Shigella causes bacillary dysentery, and it presents with abdominal cramping, tenesmus and frequent small-volume bloody stools.
2. Fever is present in 50%, and bacteremia is more frequent in HIV-infected patients.
3. HIV-infected patients are not particularly predisposed to infection with Shigella.
B. Campylobacter
1. Campylobacter occasionally involves the small bowel, but usually causes proctocolitis, with cramping and bloody diarrhea. It often causes prolonged diarrhea in HIV-infected patients.
2. Campylobacter enteritis may present with negative stool cultures, and biopsy for cultures may be necessary.
C. Clostridium difficile. This bacterium causes antibiotic-associateddiarrhea and life-threatening pseudomembranous colitis.
D. Vibrio parahaemolyticus is an important cause of acute colitis related to the ingestion of inadequately cooked or raw seafood.
E. Enterohemorrhagic or Verocytotoxin-Producing E. coli. These agents are responsible for hemorrhagic colitis, hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Outbreaks and sporadic cases have been reported.
IX. Viral Large Bowel Pathogens
A. Cytomegalovirus
1. CMV, a herpes virus, is ubiquitous in patients with AIDS. It most commonly manifests as retinitis. However, it can also cause encephalitis, pneumonia, hepatitis, adrenalitis, sinusitis, and gastrointestinal disease.
2. Risk for developing CMV disease increases when the CD4 count falls below 100 cells/µL.
3. CMV can occur anywhere from the mouth to the anus and can cause panenterocolitis in patients with AIDS. Colitis is the most common type of GI involvement.
4. Symptoms of CMV colitis include chronic diarrhea, crampy abdominal pain, weight loss, hematochezia and fever.
5. Only 30% of patients with CMV colitis have positive blood cultures. The diagnosis is made by biopsy.