Avascular necrosis in a HIV patient receiving ritonavir and inhaled fluticasone

Pollett, Simon; Graves, Bianca; Richards, Bethan; MacLeod, Colin

doi:10.1177/0956462413513747

Cited by 6 publications

(10 citation statements)

References 8 publications

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“…Similarly, a case of bilateral knee AVN in an HIV-infected man receiving inhaled fluticasone and PI was reported by Pollett et al [9].…”

Section: Discussionsupporting

confidence: 56%

“…The risk of AVN is particularly higher in patients on PI therapy; however, the mechanism is unclear [7]. A detailed search of the literature only resulted in three other cases of AVN presenting as a complication of coadministering ritonavir and fluticasone [8][9][10]. Kaviani et al reported a case of a 60-year-old man with AVN of bilateral hips in an HIV-positive patient taking ICS with ritonavir-boosted antiretroviral therapy [8].…”

Section: Discussionmentioning

confidence: 99%

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

Kant

Cromer

Chandra

et al. 2020

Cureus

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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 hormonemediated 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 HIVinfected 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.

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“…Similarly, a case of bilateral knee AVN in an HIV-infected man receiving inhaled fluticasone and PI was reported by Pollett et al [9].…”

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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

Kant

Cromer

Chandra

et al. 2020

Cureus

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show abstract

“…Osteonecrosis related to ICS use is very uncommon and available data is limited only to case reports [ 41 - 44 ]. Concomitant use of oral steroids for exacerbation of primary lung conditions such as asthma and COPD increases the risk of osteonecrosis from ICS.…”

Section: Ics and Bone Diseasementioning

confidence: 99%

“…Corticosteroids are metabolised in the liver by Cytochrome P450 enzyme (mainly CYP3A4) system and the medications that induce this enzyme system may increase the systemic bioavailability of steroids leading to toxicity. Increasing use of anti-retroviral medications such as retonavir, which are powerful CYP3A4 inducers, have been found to be associated with a higher risk of ICS-related osteonecrosis [ 43 , 44 ].…”

Section: Ics and Bone Diseasementioning

confidence: 99%

Inhaled Corticosteroids and Bone Health

Chee¹,

Sellahewa²,

Pappachan³

2015

TORMJ

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Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease.

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“…1 This may cause iatrogenic Cushing syndrome, suppression of the hypothalamic-pituitary-adrenal (HPA) axis, acute adrenal insufficiency in case of abrupt corticosteroid withdrawal, as well as hypertension, osteoporosis and avascular necrosis. [1][2][3][4][5] We report a case of iatrogenic Cushing syndrome and multifocal osteonecrosis in a patient with HIV1 infection on a ritonavir-boosted antiretroviral therapy (ART) and COPD treated with fluticasone. It is intended to emphasise the importance of the interaction between inhaled corticosteroids and cytochrome P450 (CYP450) inhibitors and its potential severe consequences.…”

Section: Introductionmentioning

confidence: 99%

Iatrogenic Cushing syndrome and multifocal osteonecrosis caused by the interaction between inhaled fluticasone and ritonavir

et al. 2020

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Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur.

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Avascular necrosis in a HIV patient receiving ritonavir and inhaled fluticasone

Cited by 6 publications

References 8 publications

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

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

Inhaled Corticosteroids and Bone Health

Iatrogenic Cushing syndrome and multifocal osteonecrosis caused by the interaction between inhaled fluticasone and ritonavir

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