Diseases of the gastrointestinal tract are common among those who are HIV-infected. Sometimes the first clue that a previously undiagnosed inmate/patient is HIV-infected is the presence of an HIV-associated gastrointestinal condition. These conditions can lead to significant morbidity including pain, difficulty swallowing, diarrhea, and weight loss. Early diagnosis and treatment can substantially improve the lives of those who are afflicted by these conditions. Although identifying the specific etiology of a patient's symptoms can be challenging, a methodical approach can usually identify a treatable condition. This article focuses on some of the most common abnormalities of the gastrointestinal system that correctional health care providers are likely to encounter among their HIV-infected patients.
Oral hairy leukoplakia (OHL) generally presents as filamentous or hairy projections on the lateral borders of the tongue. The lesions are usually poorly demarcated and can have a flattened appearance. In contrast to thrush, the lesion of OHL cannot be brushed off. Thought to be due to Epstein-Barr virus, the lesions are asymptomatic and are generally of only cosmetic importance. OHL sometimes responds to acyclovir or valacyclovir, although probably the best treatment is HAART-induced immune reconstitution. As with thrush, OHL is highly predictive of HIV infection.
Aphthous ulcers are common and often severe in those who are HIV infected. Ulcers are traditionally classified as minor (<10mm) or major (>10mm) in size, and can be single or multiple. The lesions are typically painful, well-demarcated ulcerations that can be either shallow or deep. Ulcers can be found on the buccal or labial mucosa, tongue, soft palate, or pharynx. Not uncommonly, the patient will have a tender adjacent submandibular node. Aphthous ulcers are of unknown etiology. Some clinicians recommend treatment with topical suspensions of tetracycline with or without nystatin or hydrocortisone, while others recommend topical Kenalog® in Orabase, which is a paste that will stick to the wet surfaces of the mouth and form a protective film over the mouth ulcer. Minor aphthae usually heal without scarring in <10 days regardless of therapy. Perhaps the best approach is analgesics such as ibuprofen and, prior to meals, topical viscous lidocaine. Avoidance of acidic foods such as tomatoes and citrus is also useful while lesions are present. Major aphthae can be more painful and take longer to heal. Aphthae can also present in a herpetiform pattern, with multiple small ulcerative lesions. Oral lesions that do not heal within two weeks or those that are accompanied by systemic signs such as fever should be biopsied to rule out other etiologies such as deep fungal infection or malignancy. Single shallow painless ulcerations can be due to syphilis (condyloma lata), and should be screened for with a rapid plasma reagin (RPR) test.
Warts can be found on the lips or in the oral cavity and are typically painless. Caused by human papillomavirus, lesions can be either flat or cauliflower shaped and are often multiple in number. Lesions can be removed with a scalpel, by electrosurgery, laser ablation, or liquid nitrogen. If the lesion is flat and located on the tongue, consider other potential causes, such as syphilis.
Kaposi's sarcoma (KS) can be found anywhere in the GI tract. When found in the oral cavity, KS is most commonly red, blue, or purple in color and can be either macular or nodular. Lesions are most commonly found on the hard palate, but can also be seen on the gingiva or oropharynyx. The diagnosis is made by histologic examination of tissue obtained by biopsy. The most effective treatment is immune reconstitution by HAART, but in those for whom this is not possible intralesional chemotherapeutic agents such as vinblastine have been used.
In cases of esophagitis that fail to respond to antifungal therapy, endoscopy with biopsy is required to rule out other etiologies such as herpes simplex virus, (HSV) cytomegalovirus, (CMV), malignancy, or aphthous ulcerations. Patients with CMV esophagitis commonly have systemic symptoms such as fever, nausea, emesis, diarrhea, abdominal pain, and weight loss. Biopsy reveals CMV infected cells with intranuclear inclusion bodies. CMV esophagitis can be treated intravenously with ganciclovir (5 mg/kg q 12 hours for 14 days) or foscarnet (60 mg/kg q 8 hours for 14 days). Ganciclovir can lead to myelo-suppression, while foscarnet can cause renal insufficiency, electrolyte disturbances, and penile ulcerations.
Esophageal HSV can present with odynophgia, dysphagia, retrosternal pain, nausea, and emesis. Untreated patients can develop tracheoesophageal fistulas, necrosis, stricture, or hemorrhage. Biopsy demonstrates cytoplasmic inclusion bodies, ground glass appearance of nuclei, and multinucleated giant cells. HSV responds to intravenous acyclovir.
Major aphthae involving the esophagus can persist and be significantly debilitating. In some cases, systemic steroids or oral thalidomide is useful in hastening healing.
The evaluation of a patient with diarrhea begins with a thorough history and physical examination. Patients may use the word diarrhea to describe anything from a rectal discharge, to occasional loose stools, to frequent large volume bowel movements. Additionally, acute self-limited diarrhea occurs frequently in otherwise healthy adults. Diarrhea that has been present for years with little if any weight loss is more likely to be due to irritable bowel, inflammatory bowel, or lactose intolerance than to an infectious etiology. In patients with advanced immunodeficiency, fever, and anemia, opportunistic infections such as those caused by Mycobacterium avium complex (MAC) and CMV must be considered. Medications or dietary changes are often an overlooked cause of changes in bowel frequency or consistency. In jails and prisons, regulated access to toilets and toilet paper can cause those who experience medication-induced diarrhea to adhere poorly to prescribed treatments. Drugs that commonly cause a change in bowel motility include laxatives, antacids, cardiac medications, some psychiatric medications, and antiretroviral agents such as ddI, ritonavir and nelfinavir. Antibiotics can alter intestinal flora and lead to loose stools.
In those who present with symptoms of greater than one-week duration associated with weight loss, fever, dehydration, or bloody stools, diagnostic studies are indicated. The intensity of the work-up is subject to debate, but most would agree that a stepwise approach is usually appropriate in those who are not critically ill. Generally, in HIV infected patients it is most appropriate to begin with evaluation of stool specimens for presence of ova, parasites, Clostridium difficile toxin, Salmonella, Shigella, Campylobacter, E. coli 0157 H7, Cryptosporidium, and Microsporidia. To increase the yield, it is recommended to send three separately collected specimens for ova and parasite analysis. If the patient is febrile, blood cultures for bacteria should be collected. In those with advanced immunodeficiency (CD4 <75/mm3) blood cultures for mycobacteria are also indicated. If stool studies and blood cultures fail to identify an etiology, flexible sigmoidoscopy or colonoscopy with biopsy should be performed. Biopsy specimens should be cultured for Salmonella, Shigella, Campylobacter, mycobacteria, CMV, and HSV. Histologic evaluation should include staining for mycobacteria, fungi, protozoans, and viral inclusions.
Fever is more commonly seen in Salmonella infection than in other bacterial cause of diarrhea. Blood in the stool suggest Shigella or Campylobacter rather than Salmonella. Among those infected with HIV, Salmonella is more likely to lead to bacteremic disease and to relapse after treatment. Predictors of relapse include septicemia and low CD4 lymphocyte counts. Salmonella can be treated with TMP/FMX, a quinolone, or azithromycin. Among those with CD4 counts less than 50 cells/mm3 who have experienced relapsed infection with Salmonella, ongoing maintenance therapy with ciprofloxacin should be considered. If bacterial colitis is suspected, medications that decrease bowel motility such as diphenoxylate, loperamide, paregoric, and tincture of opiates should be avoided because they have been associated with the development of toxic megacolon or prolongation of infection. Clustering of cases of bacterial diarrhea caused by Salmonella, Shigella, or E. coli 0157H7 may indicate a food borne outbreak or person-to-person transmission and should lead to an investigation.
Infection with C. difficile can lead to diarrhea in patients with AIDS. Both receiving antibiotics and being hospitalized are associated with an increased risk for C. difficile infection. Diagnosis can be made by the detection of C. difficile toxin in stool. The first line treatment is oral metronidazole at a dose of 500 mg by mouth 3X/day for 10-14 days. Because of the concern for encouraging the development of resistant organisms, oral vancomycin should be reserved for only those patients who fail to respond to metronidazole.
Disease due to MAC is uncommon among those who have a CD4 lymphocyte count of >100/mm3 and those who are taking macrolide prophylaxis. Among those with severe immunosuppression, disseminated MAC can cause diarrhea with fever, sweats, anemia, neutropenia, weight loss, and hepatosplenomegaly. Stool or blood cultures for acid-fast bacilli (AFB) can confirm the diagnosis. While culture of the organism from a tissue specimen is the gold standard for diagnosis, endoscopic biopsy showing foamy macrophages and acid-fast organisms can be used as evidence of infection as well. Cultures are necessary to differentiate MAC from tuberculosis. Treatment with combinations of medications including rifampin or rifabutin, ethambutol, ciprofloxacin, amikacin, and clarithromycin or azithromycin have been used with some success. Ultimately, the only long-term effective strategy for controlling MAC disease relies on immune restoration with HAART.
Microsporidia species are spore-forming parasites that can cause a wide variety of clinical syndromes among those who are HIV-infected. The microsporidial organisms Enterocytozoon bieneusi and Encephalitozoon intestinalis can cause diarrhea and wasting, and albendazole can be effective for treatment.
In most cases, E. histolytica is a colonizer and does not cause symptoms; however, some strains of E. histolytica can lead to cramping, abdominal pain, painful bowel movements, and bloody stools. E. histolytica is diagnosed by stool examination or blood serology. Treatment for symptomatic disease (i.e., invasive disease) is metronidazole 750 mg 3X/day for 10 days. There is disagreement as to the benefit of treating those who are asymptomatic but have been demonstrated to pass cysts. If the goal is to eradicate cysts from the intestinal lumen, the recommended treatment is iodoquinol 650 mg 3X/day for three weeks.
Giardia lamblia is an enteric protozoan with a worldwide distribution that causes acute and chronic diarrhea throughout the world. Giardiasis can be transmitted through water and person-to-person by the fecal-oral route. Most of those who ingest Giardia cysts will not become infected. Of those who are infected, some will become asymptomatic cyst passers while others will develop diarrhea. Symptoms can include cramps, diarrhea, bloating, flatulence, and weight loss. Giardia is diagnosed by the detection of cysts or trophozoites in the stool by direct examination or antigen assay. Treatment is generally metronidazole at a dose of 250 mg 3X/day for five days.
In those with advanced immunosuppression (typically CD4 counts of <50/mm3) CMV can lead to colitis, but since the introduction of HAART, the incidence of active CMV disease has fallen dramatically in the U.S. Diagnosis is usually made by flexible sigmoidoscopy or colonoscopy. CMV can lead to areas of erythema, ulceration, and hemorrhage. Histologic examination of biopsy specimens reveals intranuclear inclusion bodies in infected epithelial, endothelial, or smooth muscle cells.
Acute treatment of CMV colitis is ganciclovir IV 10-15 mg/kg/day in two to three divided doses. Foscarnet is also effective at a dose of 180 mg/kg/day IV in two or three divided doses. In the absence of immune restoration, active disease commonly recurs. In the event of relapse, retreatment followed by daily maintenance therapy is indicated. The only long term effective treatment for CMV is HAART-induced immune restoration.
|Table 1: Commonly Used Treatments for Warts|
|Treatment||How Administered||Frequency||Side Effects||Comments|
|Bichloroacetic acid (BCA) or trichloroacetic acid (TCA)||By clinician, solution applied in several thin coats to wart(s). Dries as a white "frost"||Q 1-2 weeks, up to 6 applications||Burning||Don't reapply if the area is not healed from prior treatment|
|Podophyllin 10% to 25% resin||By clinician, small amount applied to each wart, air dry||Q week until warts are gone||Pain, ulceration, scarring||Wash off several hours after application to decrease toxicity and systemic absorption|
|Podofilox 0.5% gel or solution||By patient, applied with an applicator/swab to visible warts||BID for 3 consecutive days each week||Pain, redness||No need to wash off, not for use in pregnancy|
|Imiquimod 5%||By patient, applied in thin film to warts at bedtime||Three times weekly for up to 16 weeks||Pain or ulceration||Wash off in morning|
|Alpha-interferon||By clinician, intralesional injection||Depends upon response||Fever, myalgia, flu-like symptoms||Not for use in pregnancy|
|Surgical excision||By clinician, with scalpel, scissors, laser, or electrocautery||Once||Pain, infection||Requires local or general anesthesia|
|Cryotherapy||By clinician, warts are frozen with liquid nitrogen||Q 1-2 weeks for 3-6 treatments||Pain, blistering, scarring||Most effective with several freeze-thaw cycles for 10-25 seconds per freeze|
Joseph Bick, M.D., is Chief Medical Officer at the California Medical Facility, California Department of Corrections. Disclosures: Nothing to disclose.