Resident Program - Case of the Month

Discussion

Human Immunodeficiency Virus (HIV)-Associated Gastrointestinal Disease

One of the major sites of disease in HIV infection is the gastrointestinal (GI) tract. Patients mostly present with nonspecific GI symptoms like anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea. Endoscopy is considered to be the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic examination followed by a histopathologic evaluation can render diagnoses in patients with non-specific symptoms.

Endoscopic biopsy specimens are evaluated by histopathology with light and electron microscopy, use of special stains, immunohistochemical techniques, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR). Hematoxylin and eosin (H & E) staining, is often sufficient to suggest or confirm a diagnosis. Electron microscopy may be used to identify protozoan infections of the small bowel, such as Cryptosporidia and microsporidia. Special stains can be used to highlight specific disease characteristics: periodic acid-Schiff with diastase (PASD) stains highlight acid mucopolysaccharides, glycogen, and pseudohyphae in candidiasis; Grocott’s methenamine silver (GMS) stains reveal fungal elements such as Candida, Histoplasmosis, and Cryptococcus; acid fast bacilli (AFB) stains demonstrate mycobacterial bacilli, as in mycobacterium avium-intarcellulare (MAI) infection; and Warthin-Starry stains are used for spirochetes. Immunohistochemistry, FISH, and PCR are valuable tools to identify viral infections—such as cytomegalovirus (CMV) or herpes simplex virus (HSV)—and HIV-associated neoplasia in tissue samples.

The most common mycobacterial infection affecting severely immunocompromised patients is disseminated Mycobacterium-avium intracellulare (MAI) infection, which often presents with mesenteric lymphadenitis, diffuse abdominal pain, weight loss, fever, or diarrhea. The endoscopic appearance of MAI in the upper GI tract can range from multiple raised nodules, thickened and edematous mucosal folds, occasional yellow patches, flattening of duodenal villi, ulceration, erythema, edema, friability, reduced mucosal vascularity, stricture, and aphthous erosions to normal appearing mucosa. [1] Disseminated MAI is usually seen in patients with a CD4 count of less than 50 cells/mm3. [2, 3] The risk of disseminated MAI is approximately 60% within 1 year for patients with MAI colonization in the GI tract as compared with those without GI involvement. [4]

Definitive diagnosis is established by biopsy, with demonstration of acid-fast bacilli in tissue specimens. Blood and stool cultures may also reveal MAI infection. Histopathologically, intestinal MAI infection can simulate Whipple’s disease or intestinal histoplasmosis. Both MAI and Whipple disease demonstrate periodic acid-Schiff-(PAS)-positive foamy macrophages in the lamina propria. However, in MAI, the macrophages are filled with acid-fast bacilli, Tropheryma whipplei in Whipple disease and GMS positive fungal elements in intestinal histoplasmosis. [5]  MAI affecting the colon, presents with diarrhea, malabsorption,  and flattened mucosa on endoscopic examination. Similar to upper GI tract there is a dense histiocytic infiltrate in the lamina propria simulating Crohn’s disease. As in upper GI MAI infection, acid-fast staining will confirm mycobacterial organisms.

Although the use of effective antiretroviral therapy (ART) for HIV and antimicrobial prophylaxis against MAI infection have had a major impact on the incidence and the clinical course of MAI in patients with AIDS, however, in clinical practice, patients may present with new or recurrent MAI. GI MAI infection may be the first presentation of AIDS associated opportunistic infection; so it is crucial to be aware of the endoscopic findings. Early recognition of GI MAI infection by endoscopy followed by biopsy in HIV-infected patients and initiation of anti-MAI therapy and ART may reduce significant morbidity and mortality.

References

1. Sun HY, Chen MY, Wu MS, et al. Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review. Gastrointestinal endoscopy 2005;61:775-779.
2. Chaisson RE, Moore RD, Richman DD, et al. Incidence and natural history of Mycobacterium avium-complex infections in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. The American review of respiratory disease 1992;146:285-289.
3. Nightingale SD, Byrd LT, Southern PM, et al. Incidence of Mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. The Journal of infectious diseases 1992;165:1082-1085.
4. Chin DP, Hopewell PC, Yajko DM, et al. Mycobacterium avium complex in the respiratory or gastrointestinal tract and the risk of M. avium complex bacteremia in patients with human immunodeficiency virus infection. The Journal of infectious diseases 1994;169:289-295.
5. Clayton F, Clayton CH. Gastrointestinal pathology in HIV-infected patients. Gastroenterology clinics of North America 1997;26:191-240.