Iatrogenic Cushing Syndrome in a 47-Year-Old HIV-Positive Woman on Ritonavir and Inhaled Budesonide

Iatrogenic Cushing syndrome (CS) is a well-known complication of treating patients with systemic steroids. More rarely, it has been described in HIV-positive patients on ritonavir (RTV) while using the inhaled corticosteroid fluticasone, which is metabolized through the cytochrome P450 3A4 (CYP3A4) enzyme system. In the presence of RTV, a known CYP3A4 enzyme inhibitor, the interaction can result in impaired metabolism and systemic accumulation of inhaled fluticasone resulting in iatrogenic CS. Iatrogenic CS has been less often described with inhaled budesonide compared to inhaled fluticasone. Therefore, inhaled budesonide is often used as an alternative therapy for patients on RTV to avoid iatrogenic CS. We report the fifth case report of budesonide-induced iatrogenic CS in an HIV-positive patient on RTV. We highlight the importance of early recognition of the syndrome and distinguishing it from HIV lipodystrophy. Finally, we review the literature for cases of iatrogenic CS involving RTV and commonly used steroids.

HIV-Associated Lipodystrophy and Lipoatrophy

Patients with HIV have been seen to manifest unusual changes in body habitus that constitute variable combinations of peripheral fat loss ( lipoatrophy), central fat accumulation (lipohypertrophy), and the condition known as HIV-associated lipodystrophy (HAL). Although the origins of HAL are unclear, several factors have been linked to it. Because better antiretroviral therapy (ART) drug regimens have led to increased longevity, it is possible that the natural evolution of metabolic complications of HIV is the lipodystrophic phenotype. The specific effects of antiretroviral medications have also been implicated, and the initial usage of ART in the 1990s was accompanied by multiple reports of abnormalities in body fat distribution variously termed the “protease paunch,” “crixivan belly,” among others. Other factors include immune phenomenon and effects mediated directly by the HIV virus. Despite intensive research to understand the mechanistic underpinnings of HIV lipodystrophy and lipoatrophy, the answers remain elusive.