NAPLES, FLA. — Although physicians see fewer direct cutaneous manifestations of HIV infection in this era of highly active antiretroviral treatment, the drugs themselves can cause important dermatologic reactions, according to a presentation at a symposium sponsored by the Dermatology Foundation.
Most drugs in highly active antiretroviral treatment (HAART) can cause morbilliform eruptions. Hyperpigmentation, hypersensitivity, and retinoidlike effects are among agent-specific adverse effects. Most adverse sequelae are reversible and resolve when the responsible agent is stopped, said Dr. Andrew Blauvelt, professor of dermatology at Oregon Health & Science University, Portland.
The hyperpigmentation caused by zidovudine (AZT) correlates with pigmentation and therefore occurs more often in patients of color. The drug deposits additional melanin in the epidermis and dermis, although nail and mucocutaneous pigmentation is also possible. The dose-dependent darkening is potentially reversible.
Abacavir hypersensitivity presents as morbilliform eruptions in about 10% of patients, 2%–3% of whom also experience a severe systemic reaction. Symptoms include fever, abdominal pain, nausea, diarrhea, dyspnea, cough, myalgias, arthralgias, and hypotension. “Stop the drug as soon as possible and never rechallenge the patient” with abacavir, Dr. Blauvelt said. The rash alone is not generally a reason to stop the drug. The eruptions typically appear within 6 weeks of starting abacavir and resolve when the drug is stopped.
Nevirapine can cause Stevens-Johnson syndrome. “Stevens-Johnson can occur with any of these drugs, but it is most commonly reported with nevirapine,” he said. Early identification is possible. Some patients complain of mucosal problems, particularly eye, mouth, and/or genital area symptoms before they develop full-blown Stevens-Johnson syndrome. “For me there is a role for systemic steroids in Stevens-Johnson, but only if it is an early case. This is still a controversial area.”
Morbilliform eruptions appear in 19% of patients treated with nevirapine, including 8% who develop Stevens-Johnson syndrome, “a pretty high number,” Dr. Blauvelt said.
Dr. Blauvelt suggested starting the drug at lower doses and increasing it gradually to prevent drug reactions. If a nevirapine-treated patient has a reaction, never rechallenge them with the same drug, he added.
Indinavir, ritonavir, stavudine, and zidovudine can cause lipodystrophy. “It's controversial which agents are the most likely culprits for causing lipodystrophy,” he said. In his opinion, indinavir is No. 1.
“You have probably seen this if you have any people with HIV in your practice,” Dr. Blauvelt said. Although lipodystrophy can cause breast enlargement, buffalo hump, and abdominal protuberance, dermatologists are most likely to see patients with facial atrophy. Lipodystrophy generally occurs within 6–12 months of initiation of therapy, and like other drug reactions, is potentially reversible, he said.
Indinavir can cause retinoidlike effects that include recurrent paronychia, pyogenic granulomas, and alopecia. The etiology is unknown, Dr. Blauvelt said, but the effects might be caused by similarities in binding proteins between HIV protease and retinoic acid.
For more information about HAART, visit www.aidsinfo.nih.gov
Stevens-Johnson syndrome, which can be caused by nevirapine or other HAART agents, may start with mucosal symptoms involving the mouth, eyes, or genital area. Courtesy Dr. Andrew Blauvelt