EVALUATION AND MANAGEMENT

A specific cause of esophageal complaints in the AIDS patient cannot be made on the basis of symptoms or physical examination alone (Table 33-1). Nevertheless, a few generalizations may be made. The presence of oral thrush associated with mild to moderate dysphagia without odynophagia is likely caused by Candida esophagitis. In contrast, the patient with severe odynophagia without dysphagia or thrush is more likely to have ulcerative esophagitis (viral, idiopathic). The patient complaining of substernal burning and regurgitation is most likely to have gastroesophageal reflux disease. Intermittent solid and liquid dysphagia may be related to a motility disturbance.¹³

Table 33-1 Differential Diagnosis of Dysphagia and Odynophagia in Patients with AIDS

* More frequent cause.

Endoscopy with biopsy is the only means of establishing a specific etiology for the cause of dysphagia and odynophagia. Conventional barium swallow radiography in the patient with esophageal complaints is not worthwhile, although it may reveal typical features of Candida, CMV, or herpes. In addition, the radiographic appearance of an esophageal ulcer cannot adequately distinguish etiology, thus mandating subsequent endoscopy and biopsy for a definitive diagnosis. Multiple mucosal biopsies are preferred over brush cytology for ulcerated lesions.¹²

Given the preponderance of Candida infection, an empirical approach to the management of esophageal symptoms is reasonable in most patients with AIDS. Patients with dysphagia and/or odynophagia who also have oral thrush should be treated empirically with fluconazole 100 mg/day after a 200-mg loading dose.¹⁴ Itraconazole or fluconazole suspensions are effective alternatives. If symptoms persist despite a 1-week empirical trial, endoscopy with biopsy should be performed in preference to the initiation of other empirical trials or escalation of the dose of fluconazole. Narcotics are appropriate for the patient with severe pain until specific treatment for the underlying cause can be initiated. Relapse of Candida esophagitis is invariable unless immune function is improved with antiretroviral treatment. Despite chronic prophylaxis, relapse frequently occurs often due to antifungal resistance. This is much less of a problem now that patients are receiving HAART. In the absence of HAART, caspofungin and posaconazole may be effective for patients with resistance to antifungal drugs.¹⁵

CMV and HSV infection should be treated similarly to other gut involvement with these viruses (see following). Idiopathic ulcers respond in more than 90% of patients to oral glucocorticoids (e.g., 40 mg prednisone per day initially, tapered over 4 weeks).¹⁶ The basis for glucocorticoid efficacy is unknown; infectious causes should be assiduously excluded before administering gluocorticoids in this setting. Thalidomide is also highly effective and may be curative when prednisone fails.¹⁶ The main side effects of thalidomide are somnolence, rash, and neuropathy. The devastating teratogenic effects mandate its use to be limited to men.

EVALUATION AND MANAGEMENT

Protozoa account for the most prevalent class of diarrheal pathogens in most series,¹⁸ largely because many of these infections can lead to chronic diarrhea and are refractory to treatment. Cryptosporidium, a cause of self-limited diarrhea in healthy hosts, remains the most frequent protozoa identified in HIV-infected patients worldwide.¹⁸ Clinical presentation and outcome are related to the degree of immunocompromise and the subtype of organism.¹⁹ Stool testing of asymptomatic individuals shows a high carriage rate because some subtypes appear to be less pathogenic.²⁰ The small bowel is the most common site of infection, although the organisms can be recovered in all regions of the gut, as well as in biliary and respiratory epithelium. Diarrhea is typically severe, with stool volumes of several liters per day not uncommon. Borborygmi, nausea, and weight loss are frequently associated symptoms; right upper quadrant pain suggests biliary tract involvement (see later). The pathogenesis of this infection is uncertain. The diagnosis of intestinal cryptosporidiosis is most often made by acid-fast stain of the stool, where the organisms appear as bright red spherules, similar in size to red blood cells. The sensitivity of stool testing varies and depends on the burden of organisms, character of the stool (formed versus liquid), and primary site of infection. Stool antigen detection and polymerase chain reaction (PCR) markedly increase sensitivity of stool testing. Cryptosporidia may be identified in small bowel or rectal biopsies even when the stool examination is negative.²¹

Specific antimicrobial treatment of cryptosporidial infection remains disappointing. Numerous antimicrobial agents have been tested, most without significant effect (Table 33-3). Nitazoxanide and azithromycin have been most recently evaluated with mixed results, and combination therapies have also been used. Nitazoxanide can lead to cryptosporidial oocyte clearance in HIV-seronegative patients but has not shown efficacy in HIV-infected patients.²² Although not pathogen-specific, currently the most effective therapy for cryptosporidia is HAART, in which improvement of immune function results in a clinical remission of diarrhea and clearance of cryptosporidia from the stool and on small bowel biopsy.²³ For patients failing HAART and/or in whom antimicrobial therapy is ineffective, symptomatic treatment should include fluid support, antidiarrheal agents, and occasionally narcotics such as tincture of opium to control the diarrhea.

Table 33-3 Treatment of Infectious Causes of Diarrhea in Patients with AIDS

* Duration of therapy dictated by immune reconstitution with highly active antiretroviral therapy.

† Molina JM, Tourneur M, Sarfati C, et al. Fumagillin treatment of intestinal microsporidiosis. N Engl J Med 2002; 346:1963.

Isospora belli is a sporozoan, which, like Cryptosporidium, is a cause of chronic diarrhea in untreated patients with HIV infection. The disease is rare in the United States, but it is more frequent and endemic in developing countries such as Haiti. The organism may be identified by acid-fast stain of the stool or duodenal secretions or on mucosal biopsy. This infection can be effectively treated with antibiotics, specifically trimethoprim-sulfamethoxazole and ciprofloxacin.²⁴

Microsporidia emerged as common intestinal infections in AIDS, but their prevalence has markedly fallen in the HAART era.²⁵ Intestinal and hepatobiliary disease may be caused by two species of microsporidia: Enterocytozoon bieneusi and Encephalitozoon intestinalis. The reported prevalence of microsporidia without HAART varied from 15% to 39%.^18,21,26 Typical symptoms include watery, nonbloody diarrhea of mild to moderate severity usually without associated crampy abdominal pain. Weight loss is common, although not to the degree observed with Cryptosporidium. Infection is associated with severe immunodeficiency with median CD4 counts of infected individuals of less than 100/mm³.²⁶ As with infection from cryptosporidia, the pathogenesis of disease remains poorly defined. The organism incites little tissue inflammation and is rarely associated with villous atrophy and cell degeneration. Microsporidia can be discerned by light microscopy when tissue is embedded in plastic or paraffin (Fig. 33-5). Staining of embedded mucosal biopsies with Brown-Brenn, Gram stain, or modified Masson trichrome stain is superior to routine hematoxylin and eosin staining.²⁷ E. intestinalis can usually be differentiated from E. bieneusi by its larger size and infection of lamina propria macrophages; electron microscopy is definitive. Stool staining techniques are only moderately sensitive, while small bowel biopsies are generally positive. No effective therapy is available for E. bieneusi, whereas albendazole is effective for E. intestinalis.²⁸ As with the treatment of cryptosporidia, HAART is the best therapy, resulting in resolution of diarrhea with loss of this pathogen from stool and on small bowel biopsy.²³

Figure 33-5. Endoscopic biopsy specimen of small bowel microsporidiosis. This thin plastic section demonstrates shedding of an epithelial cell containing microsporidial oocysts.

(From Gazzard BG. Diarrhea in human immunodeficiency virus antibody-positive patients. Semin Gastroenterol 1991;2:3.)

For unclear reasons, infections by the protozoa Giardia lamblia and Entamoeba histolytica are not consistently seen with increased frequency or virulence in AIDS.²⁹ However, in a study from Taiwan, where E. histolytica is endemic, amebic colitis was identified as a common cause of diarrhea.³⁰ The nonpathogenic Entamoeba dispar is morphologically similar to E. histolytica and can only be distinguished by more specific stool or enzyme-linked immunosorbent assay tests.²⁹ Blastocystis hominis, Endolimax nana, and Entamoeba coli are nonpathogenic protozoa that are seen more commonly in men who have sex with men and are often found in association with other protozoal parasites. Rare cases of enteric leishmaniasis, Pneumocystis jiroveci infection, and toxoplasmosis have been reported.

Helminths, particularly Strongyloides stercoralis and Ascaris lumbricoides, are uncommon pathogens.³¹ Patients may present with abdominal pain, diarrhea, and eosinophilia. The clinical syndrome and recurrence rate associated with these parasites do not appear to be altered in the setting of HIV infection.

Viral infection of the large bowel, and rarely the small bowel, is an important cause of diarrhea in HIV infection. CMV is the most common viral cause of diarrhea and the most frequent cause of chronic diarrhea in patients with AIDS and multiple negative stool tests.³² This infection characteristically occurs late in the course of HIV infection when the CD4 lymphocyte count falls below 100/L (see Fig. 33-1). Infection is most common in the colon (Fig. 33-6), but concomitant disease in the esophagus, stomach, or small bowel may be observed. Isolated small bowel disease typically results in abdominal pain rather than diarrheal illness. The pathogenesis has not been totally elucidated. Infection of vascular endothelial cells is common, suggesting a role for mucosal ischemia; true histopathologic evidence of vasculitis is rare. An important role for local proinflammatory cytokine activation has been suggested.³³

Figure 33-6. Cytomegalovirus colitis. Endoscopic photograph of the sigmoid colon showing edema and diffuse subepithelial hemorrhage typical for cytomegalovirus. This endoscopic appearance is similar to that of idiopathic ulcerative colitis.

The clinical manifestations of enteric CMV infection vary greatly and include asymptomatic carriage, nonspecific symptoms of weight loss and fevers, and focal enteritis/colitis including appendicitis or diffuse ulcerating hemorrhagic involvement with bleeding or perforation. As a result, patients can present with one of several constellations of symptoms, including abdominal pain; peritonitis; watery, nonbloody diarrhea; or hematochezia.³⁴ The most common presentation, however, is abdominal pain associated with chronic diarrhea. Although the endoscopic spectrum is variable, the hallmark of CMV enteritis/colitis is subepithelial hemorrhage and mucosal ulceration (see Fig. 33-6).³⁴

The diagnosis of GI CMV infection is best established by demonstrating viral cytopathic effect in tissue specimens.³⁵ The inclusions may be atypical in appearance or few in number, requiring immunostaining and/or in situ hybridization for confirmation.³⁵ Cultures for CMV are usually positive when inclusions are present, but they are less sensitive and specific for CMV infection than histopathologic identification. If inclusions are few in number and are demonstrable in tissue that appears macroscopically normal, the patient should be considered to have CMV colonization rather than true CMV infection.

A number of effective therapies are available for the treatment of CMV (see Table 33-3). The most commonly used agent is ganciclovir, an acyclovir derivative, which is effective in approximately 75% of cases.³⁶ Ganciclovir requires daily intravenous administration for several weeks, depending on the location and severity of disease. Valganciclovir, an oral analog of ganciclovir, has excellent GI absorption and efficacy for CMV retinitis, but has not been well studied for induction therapy in GI disease. Valganciclovir has become widely used as preemptive therapy in the transplant setting and has shown promise as first-line therapy.³⁷

Related posts:

Surgical Peritonitis and Other Diseases of the Peritoneum, Mesentery, Omentum, and Diaphragm Hepatitis Caused by Other Viruses Diarrhea Small Intestinal Motor and Sensory Function and Dysfunction Diverticular Disease of the Colon Diseases of the Anorectum

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