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Investigation of Diarrhea in AIDS

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Investigation of Diarrhea in AIDS Color profile: _DEFAULT.CCM - Generic CMYK Composite Default screen MINI-REVIEW 100 100 95 95 75 75 25 25 5 5 0 0 Investigation of diarrhea in AIDS Klaus E Mönkemüller MD, C Mel Wilcox MD KE Mönkemüller, CM Wilcox. Investigation of diarrhea in Étude de la diarrhée liée au SIDA AIDS. Can J Gastroenterol 2000;14(11):933-940. Chronic di- arrhea is a common problem in patients with acquired immune de- RÉSUMÉ : La diarrhée chronique est un problème courant chez les pa- ficiency syndrome (AIDS), resulting in significant morbidity and tients qui souffrent du syndrome d’immunodéficience acquise (SIDA), le potential mortality. In the early stages of immunodeficiency, hu- phénomène s’accompagne d’une morbidité importante et d’une mortalité man immunodeficiency virus (HIV)-infected patients are suscep- potentielle. Au premier stade de l’immunodéficience, les patients infectés tible to infection with the same enteric pathogens that cause par le VIH sont sujets à l’infection causée par les mêmes organismes patho- diarrhea in immunocompetent hosts, but with progressive immu- gènes entériques qui provoquent la diarrhée chez des hôtes immunocom- nodeficiency, these patients become susceptible to numerous op- pétents. Mais, compte tenu de l’immunodéficience progressive, ces portunistic disorders. The main factor to consider when tailoring patients deviennent plus sujets à de nombreuses infections opportunistes. Le principal facteur dont il faut tenir compte lorsque l’on ajuste le traite- the work-up of diarrhea in the HIV-infected patient is the immune ment de la diarrhée chez les patients infectés par le VIH est le statut immu- status, which is reflected by the total CD4 lymphocyte cell count. nitaire dont témoigne la numération totale des lymphocytes CD4. Une A CD4 count of less than 100 cells/µL is significantly correlated numération de CD4 inférieure à 100/µL est en corrélation significative with opportunistic disorders. For the HIV-infected patient with avec les troubles opportunistes. Pour les patients infectés par le VIH qui diarrhea, repeated stool studies to investigate for bacteria, ova and souffrent de diarrhée, des analyses de selles répétées dans le but d’identifier parasites should be the first step. When either upper or lower gas- les bactéries, les œufs et les parasites, devraient être la première étape. En trointestinal tract symptoms are present and stool studies are nega- présence de symptômes des voies digestives hautes ou basses et de résultats tive, endoscopy directed to the probable organ of involvement is d’analyses de selles négatives, l’endoscopie dirigée vers l’organe probable- appropriate. If localizing symptoms are absent, the most appropri- ment atteint est appropriée. En l’absence de symptômes localisés, le test le ate next test is sigmoidoscopy with biopsies. Not infrequently, de- plus approprié est alors la sigmoïdoscopie avec biopsie. Il n’est pas rare, spite extensive evaluation, the cause of diarrhea in patients with malgré une évaluation approfondie, que la cause de la diarrhée liée au sida AIDS remains unexplained. Recently, the widespread use of nous échappe. Récemment, l’utilisation répandue de traitements antiré- highly active antiretroviral therapy, including protease inhibitors, troviraux hautement actifs, y compris les inhibiteurs de la protéase, ont has led to a change in the epidemiology of diarrhea in AIDS amené des changements dans l’épidémiologie de la diarrhée liée au sida. À patients. As their immune status improves, HIV-infected patients mesure que le statut immunitaire des patients infectés par le VIH traités par treated with combination therapy become less prone to opportun- polythérapie s’améliore, ils deviennent moins sujets aux infections oppor- istic disorders. However, diarrhea appears to be frequent because tunistes. Par contre, la diarrhée semble fréquente, étant donné que plu- 100 several antiretroviral agents can themselves cause diarrhea. sieurs agents antirétroviraux peuvent la causer. 100 95 Key Words: AIDS; Diarrhea; Endoscopy; HIV; Immunodeficiency 95 75 75 This mini-review was prepared from a presentation made at the World Congress of Gastroenterology, Vienna, Austria, September 6 to 11, 1998 Department of Medicine, Division of Gastroenterology and Hepatology, Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, USA 25 Correspondence: Dr C Mel Wilcox, University of Alabama at Birmingham, Division of Gastroenterology and Hepatology, Birmingham, Alabama 25 35294-0007, USA. Telephone 205-934-6110, fax 205-934-1546, e-mail [email protected] 5 Received for publication October 4, 1999. Accepted October 12, 1999 5 0 0 Can J Gastroenterol Vol 14 No 11 December 2000 933 1 G:...monkemuller.vp Mon Dec 04 15:53:12 2000 Color profile: _DEFAULT.CCM - Generic CMYK Composite Default screen Mönkemüller and Wilcox 100 100 TABLE 1 95 iarrhea is a common problem in patients with acquired 95 Enteric pathogens in acquired immune deficiency syndrome Dimmune deficiency syndrome (AIDS), occurring in 75 50% of human immunodeficiency virus (HIV)-infected pa- Viruses 75 tients in North America and up to 100% of HIV-infected pa- Cytomegalovirus tients living in developing countries (1-3). Chronic diarrhea Astrovirus Picornavirus 25 results in significant morbidity and mortality, reduced qual- 25 ity of life and higher health care expenditures (4,5). In the Coronavirus 5 early stages of immunodeficiency, HIV-infected patients are Rotavirus 5 susceptible to infection by the same enteric pathogens that Herpesvirus 0 0 cause diarrhea in the immunocompetent host, but with pro- Adenovirus gressive immunodeficiency, these patients become suscepti- Small round virus ble to a wide variety of opportunistic agents (1-3,5). In Human immunodeficiency virus general, most opportunistic disorders are not observed until Bacteria the CD4 count falls below 200 cells/µL, and typically less Salmonella species than 100 cells/µL (5). Shigella species The widespread use of highly active antiretroviral ther- Campylobacter species apy, which usually includes a protease inhibitor (highly ac- Clostridium difficile tive antiretroviral therapy [HAART]), has affected the Mycobacterium avium complex epidemiology of diarrhea in AIDS (6,7). As the immune Treponema pallidum status of HIV-infected patients treated with HAART im- Spirochaetes proves, they become less prone to opportunistic disorders, Neisseria gonorrheae and the etiology of diarrhea parallels that seen in immuno- Vibrio cholerae competent patients. Also, several antiretroviral agents can Pseudomonas species* themselves cause diarrhea (8). Thus, because of HAART, Staphylococcus aureus the management of these patients has changed. Parasites The identification of enteric pathogens is important be- Giardia lamblia cause of the therapeutic regimens that have become avail- Entamoeba histolytica able to treat many of these infections (1,9,10). Despite Microsporidia extensive evaluation, however, a cause of diarrhea in pa- Enterocytozoon bieneusi tients with AIDS is not always found (11). Several investiga- Encephalitozoon intestinalis tors have proposed various approaches for the work-up of Cyclospora diarrhea in AIDS (12-16). Many of these suggested ap- Cryptosporidium proaches have been derived from retrospective analysis, and Isospora belli few have been prospectively validated (12,14). A thorough Blastocystis hominis* understanding of the etiology, epidemiology and clinical Fungi presentation of the various causes of diarrhea in AIDS is es- Histoplasma species sential so that a logical evaluation can be undertaken. In this Candida albicans review, we present current approaches to the evaluation of *The pathogenicity of these organisms has been questioned diarrhea in HIV-infected patients. ETIOLOGY The list of pathogens that can cause diarrhea in patients with count less than 100 cells/µL (5,7,13,18). CMV has been AIDS is broad (Table 1), and the most important etiological identified in mucosal biopsies in as many as 45% of patients agents are discussed individually. The most common causes with AIDS and diarrhea (19-22). A number of other viruses of diarrhea in HIV-infected patients are enteric bacteria, in- have been reported to involve the gastrointestinal tract in cluding Shigella flexneri, Salmonella enteritidis, Campylobacter AIDS patients, including adenovirus, rotavirus, astrovirus, jejuni and Clostridium difficile. Cytomegalovirus (CMV), picobirna virus and coronavirus (23). There are also reports Mycobacterium avium 100 cryptosporidiosis, microsporidia and that HIV itself can be isolated from enterocytes and colonic 100 complex (MAC) are important pathogens only in patients cells, and that HIV may have a direct cytopathic effect on the 95 with advanced immunosuppression (17). Neoplasms such as intestinal mucosa, resulting in enteropathy (24). 95 Kaposi’s sarcoma or lymphoma, and fungi such as histoplas- Bacteria: The spectrum of bacterial pathogens causing diar- 75 mosis are rare causes of diarrhea. More recently, medica- rhea in HIV-infected patients is similar to those that cause 75 tions, usually protease inhibitors, have become important diarrhea in the non-HIV-infected host. The most frequently causes of chronic diarrhea (5,8). identified pathogens are Campylobacter species, Salmonella 25 Viruses: CMV is one of the most common opportunistic in- species, Shigella species and C difficile (25,26). Yersinia entero- 25 fections in patients with AIDS, occurring late in the course of colitica, Staphylococcus aureus and Aeromonas
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