Avascular Necrosis of Both Hips From Iatrogenic Cushing 's Syndrome due to Coadministration of Fluticasone and Ritonavir in an HIV-Infected Patient

We report a case of avascular necrosis (AVN), hypercalcemia, and iatrogenic Cushing's syndrome in an HIV-positive patient taking inhaled (ICS) and nasal corticosteroids fluticasone and ritonavir. A 45-year-old HIV-infected African-American woman was seen for initial evaluation for multinodular goiter in December 2015. Relevant medications were ritonavir, raltegravir, darunavir, fluticasone propionate HFA, and nasal fluticasone propionate. Physical examination revealed classical cushingoid appearance but laboratory testing showed abnormal adrenocorticotropic hormone (ACTH) stimulation test. A diagnosis of iatrogenic Cushing's syndrome due to inhibition of fluticasone metabolism from protease inhibitor (PI) therapy with secondary adrenal suppression was made. Fluticasone nasal spray and HFA were discontinued and hydrocortisone replacement dose was initiated. The patient's Cushing's related symptoms improved over several months. Follow-up evaluation showed non-parathyroid hormone-mediated hypercalcemia. A detailed laboratory evaluation looking for the etiology for hypercalcemia was unremarkable except for an elevated urine N-telopeptide/creatinine ratio. Meanwhile, the patient developed a new symptom of hip pain. MRI of both hips showed bilateral AVN. Sickle cell screen was negative and a right hip replacement was completed in May 2017. Since this is the fourth case report of AVN from iatrogenic Cushing's syndrome in an HIV-infected patient taking a PI and ICS concomitantly, there is more likely a causal relationship and not simply a coincidental finding. Extreme caution should be used when considering any ICS therapy in combination with PIs in HIV-infected patients.

Keywords: avascular necrosis (avn); avascular osteonecrosis; drug-drug interactions; fluticasone; general medicine pharmacology; hiv; iatrogenic cushing’s syndrome; inhaled corticosteroids; protease inhibitors; ritonavir.