HIV/AIDS Enteropathy
Up to 50% of HIV patients in the United States report diarrhea, but a distinct cause is identified in only 60% to 70% of these cases. HIV enteropathy is characterized by chronic diarrhea lasting more than 4 weeks and accompanied by malabsorption and abdominal discomfort. As is characteristic of small bowel diarrhea, stools are typically voluminous and may occur postprandially. There may be marked electrolyte disturbances, severe dehydration, and unintentional weight loss.
The
mechanism by which HIV exerts its effect is not clearly elucidated. Mucosal
biopsies demonstrate an increase in stem cells leading to crypt hyperplasia
with encroachment of crypt cells into the villi, causing a decrease in the
surface area–to-volume ratio. HIV may cause a transient decrease in the
activity of several brush-border enzymes, including lactase activity, as well
as diminished sodium/glucose cotransporter activity, causing sugar
malabsorption. Together these suggest an osmotically mediated mechanism at
play. Also observed is a profound decrease in the CD4+ T lymphocytes within the
lamina propria and Peyer patches within gut-associated lymphoid tissue, which
is responsible for the defense against intestinal pathogens and the development
of tolerance to food antigens and normal commensal microbiota. Indeed, in vitro
studies have demonstrated a delay in epithelial cell differentiation, which may
contribute to tight junction disorganization and a leaky gut phenomenon, which
may promote microbial translocation across the intestinal wall. Also observed
are elevated levels of plasma lipopolysaccharide, an endotoxin produced by
bacteria in the serum of HIV patients. This proinflammatory state is thought to
stimulate immune activation and perpetuate chronic inflammation.
Initial
stool assessment should include routine stool culture, but additional tests
should assess for C. difficile infection. Also, three stool samples
separated by at least 24 hours are necessary to assess for ovas and parasites.
Additional enteric stool assays should include investigation for giardiasis and
cryptosporidiosis. In the male homosexual population, anal receptive
intercourse pre-disposes to lower intestinal colonization with Cryptosporidium,
as well as other sexually transmitted diseases such as infection due to Chlamydia
and Neisseria gonorrhoeae. These latter organisms typically create a
proctitis characterized by urgency, tenesmus, and bloody diarrhea. In the
presence of AIDS, additional specific tests should be considered, including Microsporidium,
Cystoisospora, Cyclospora, and Mycobacterium avium complex.
Viruses such as adenovirus, echovirus, and cytomegalovirus are found with
increasing frequency in HIV patients. Protozoal assessment for Entamoeba
histolytica may be conducted via stool microscopy or fecal immunoassay.
Candidal overgrowth is rare but has been reported in the literature. Other
fungal infections should be ruled out as well (see table at right).
If
laboratory or stool testing is nonrevealing, endoscopic investigation is
certainly warranted. The mucosa may appear completely intact without any overt
endoscopic inflammation. In addition to colonic biopsies, duodenal and ileal
biopsy specimens should be collected to assess the villous height–to–crypt
length ratio. Microscopic findings may be patchy, and multiple biopsies are
encouraged. If inflammation or focal lesions are observed, staining for
acid-fast bacilli should be performed to exclude the great masquerader, Mycobacterium
tuberculosis. Rarely, intestinal Kaposi sarcoma or lymphoma may be
discovered. In the event of a negative workup,
careful attention should be focused on the individual patient’s antiretroviral
therapy regimen. Multiple protease inhibitors have demonstrated diarrhea as a
potential adverse reaction that is reversible upon drug withdrawal.
Management
of the underlying viral infection with antiretroviral therapy is the
cornerstone of treatment. Because the volume loss accompanying HIV enteropathy
can be quite severe, aggressive volume replacement and expectant electrolyte
repletion are important. Of course, nutrition should be promptly reinstituted.
Lactose avoidance and fiber introduction may provide some benefit in regard to
lessening diarrheal losses and frequency.
Symptomatic control with antimotility agents such as loperamide, diphenoxylate
with atropine, or codeine phosphate may also prove useful. Crofelemer, a novel
chloride secretion antagonist, has demonstrated a decrease in noninfectious
secretory diarrhea in HIV patients. Limited data exist regarding octreotide for
the control of intestinal fluid secretion, but the drug may be of benefit in
refractory diarrhea.
Ultimately, HIV enteropathy is a diagnosis of exclusion that demands careful scrutiny of the patient’s clinical history, individualized risk factors, laboratory studies, stool studies, and medications. Immune reconstitution will help ameliorate the condition.
