Research Article
Gregor John, Diana Ollo, Pa
Abstract
Background: Iatrogenic Cushing Syndrome (ICS) has been reported after co-administration of injectedtriamcinolone and ritonavir. Clinical evolution is however poorly described and recommendations on how to manage this drug-drug interaction are lacking. Methods: We performed a systematic review of all reported cases of ICS exploring Pubmed, Embase, Cochrane library, and articles references. Time to Hypothalamic-Pituitary-Adrenal (HPA) axis recovery for patients with or without ritonavir interruption, was compared in a Cox model adjusted for confounding factors. Results: Twenty-four cases of injected triamcinolone induced ICS have been reported. 11/24 cases were related to an epidural injection, 7/24 to an intra-articular, 3/24 to an intramuscular and 3/24 to other injection sites. Symptoms started within 2 weeks (IQR: 0.8-2.3) after steroids injection and needed 11 weeks (IQR: 8-21) to resolve. HPA axis suppression lasted beyond clinical recovery, for a median of 23 (IQR: 12-28) weeks after triamcinolone injection. In a multivariate Cox model, time to HPA axis recovery was shortened when ritonavir was withheld (HR of 18.6 (CI 95% 2.4-145.1), p<0.01) and was prolonged for higher dose of injected-triamcinolone (HR 0.9 (CI 95% 0.9-1), p=0.03) and dose of ritonavir superior to100mg (HR 0.2 (CI 95% 0.04-0.9, p=0.04). Nineteen out of 24 cases (79%) encountered a medical complication related to steroids excess or HPA axis suppression. Although 42% of cases were offered steroids replacement, only 4/24 experienced symptomatic adrenal insufficiency. Conclusion: ICS is associated with frequent complications. HPA axis recovery depends on steroids and ritonavir doses, and is accelerated when ritonavir is discontinued. HPA axis replacement therapy is rarely necessary.