Since 1998, many cases of antiretroviral
therapy-related
paronychia of the toes or fingers and ingrown toenails have been reported. Most of them were related to
indinavir. Other
indinavir-induced mucocutaneous disorders resembling the adverse effects of systemic
retinoid therapy have also been reported. Although there is some uncertainty in the literature regarding a cause-effect relationship, results of several epidemiological and in vitro studies, together with cumulated clinical experience leave no doubt that
indinavir causes a
retinoid-like effect and nail alterations. Indeed,
indinavir is the only antiretroviral drug that produces these disorders, although
ritonavir may enhance
indinavir-induced
retinoid-like effects through pharmacokinetic interactions leading to increased plasma
indinavir concentrations. Approximately 30% of patients receiving
indinavir show two or more
retinoid-like manifestations and 4-9% develop
paronychia. These adverse effects are not related to other epidemiological variables such as the patient's sex, age or other risk factors or immune status. They seem to be exposure dependent and, therefore, largely dose-dependent. Chronic
paronychia is considered generally to be caused by contact irritants and candidal
infection. Nevertheless,
indinavir is currently the most frequent cause of chronic or recurrent
paronychia in HIV-infected patients. In addition,
retinoid-like manifestations such as cutaneous xerosis and
cheilitis are frequent mucocutaneous adverse effects related to
indinavir. The exact mechanism of
indinavir-induced
retinoid-like effects is unclear. Hypotheses for pathogenesis include interference with
retinoid metabolism by enhancing the
retinoic acid signalling pathway, or by increasing
retinoic acid synthesis, or by reducing
cytochrome p450-mediated
retinoic acid oxidative metabolism. Replacement of
therapy by an antiretroviral regimen not containing
indinavir, while retaining other
protease inhibitors and
lamivudine, resolves
retinoid-like manifestations without recurrences.