Developments in Glucocorticoid Therapy

Autoimmune sensorineural hearing loss (ASHL) is a rare disease of uncertain etiology, with no established treatment strategy. The duration of morbidity is increased in refractory cases; and therefore, the preservation of hearing and the prevention of adverse effects with steroid therapy are serious long term issues to consider. Long-term follow up of patients treated for ASHL was performed retrospectively in order to elucidate the pathogenesis of ASHL, evaluate the consequences of steroid therapy, and determine a promising treatment course. The cohort in this study consists of four female patients with refractory ASHL that were followed for 16–26 years. Three patients already had profound deafness on one side, probably due to ASHL, before the initiation of steroid treatment. ASHL was managed with steroid administration and the hearing was evaluated through regular audiometric tests (173–212 times). The relationship between pure tone threshold average and steroid dose was reviewed over a long-term follow-up period for each patient. During follow-up, hearing deficit progressed rapidly several times in all patients, as did responsiveness to steroid therapy. Long-term high-dose steroid therapy was not required for hearing maintenance. Hearing thresholds were nearly maintained in three patients during the 16- to 21- year follow-up, and gradually declined over a 26-year follow-up period in one patient. Considering the progress due to presbycusis, the maintenance of hearing was considered sufficient in all patients. No serious adverse effects were observed in any of the patients. Management of patients affected by ASHL with regular audiometry allowed for hearing maintenance without the morbidity of prolonged steroid therapy. The current observations give insight into the pathogenesis of ASHL pathogenesis and establish an efficient course of treatment.

As physicians prescribing systemic medications that can have preventable and treatable adverse effects, it is important for dermatologists to be aware of potential issues and to take appropriate preventative measures. Bisphosphonates may be indicated for patients on courses of corticosteroids for 3 months or longer, in addition to calcium and vitamin D supplementation. Systemic retinoids and cyclosporine can induce hyperlipidemia, and bexarotene can cause hypothyroidism. These potential adverse effects, monitoring, prevention, and treatments are discussed in further detail. Although dermatologists may often collaborate with other specialties for these issues, one must be aware of potential adverse effects and how to monitor for and/or prevent them.

Glucocorticoid-induced osteoporosis (GIOP) remains the most common form of drug-induced osteoporosis. Patients may fracture at a different bone mineral density (BMD) threshold and absolute fracture risk using FRAX should be adjusted for glucocorticoid dose. Sufficient calcium and vitamin D are necessary but are generally insufficient for higher risk persons. The use of bone therapy in GIOP is motivated by an understanding of GIOP pathophysiology, including effects on heightened bone resorption and reduced bone formation. Osteoblast and osteocyte apoptosis contributes to both GIOP and glucocorticoid-associated osteonecrosis. Bisphosphonates, teriparatide, raloxifene, and denosumab stabilize or improve BMD more than placebo. Teriparatide, zoledronic acid, and denosumab increased BMD more so than an oral bisphosphonate. Teriparatide also reduced a small number of vertebral fractures more so than risedronate. All drugs tested in GIOP have had reasonable safety profiles, considering the significant comorbidity burden of those being treated with glucocorticoids. International guidelines advocate early and aggressive management of GIOP in order to lower fracture morbidity.

Glucocorticoids (GC) are commonly used in rheumatoid arthritis (RA) patients which bears a risk of hepatitis B virus (HBV) reactivation. The purpose of this study was to investigate the risk of HBV-related mortality under long-term low-dose GCs in Taiwanese RA patients.

We retrospectively analyzed 45,423 RA patients using National Health Insurance Research Database from January 1999 to December 2011. Of them, 2204 patients had the diagnosis of HBV and were classified into four groups according to GCs regimens. Outcome comparison by Cox model analysis for liver-related mortality was performed.

In this cohort, 90.5% were older than 40. One hundred and five patients had been treated with short-term large-dose GCs (Group A); 862 patients received GCs ≥20 mg/day for ≥3 days or a variable dose but did not meet Group C criteria (Group B); 689 patients were continuously treated with low-dose (<20 mg/day) GCs for ≥3 months for at least one session (Group C); and 548 patients had never been exposed to GCs (Group D). Two hundred and sixty-one patients had been exposed to antiviral agents, which was significantly higher in Group C. Fifty-eight patients (2.63%) died of acute hepatic failure, while no statistically significant difference between each groups (p = 0.074). Groups C and D comparison by two-sample test showed that long-term low-dose GC treatment was not associated with liver-related death after adjusting for malignancy.

Long-term low-dose GC treatment was not associated with liver-related mortality in RA with concomitant HBV patients probably due to commonly applied antiviral therapy by rheumatologists.

More than 70 years ago, osteoporosis associated with endogenous glucocorticoid excess was described by Harvey Cushing. More common is the increased fracture risk associated with exogenous glucocorticoids, a therapy used for many inflammatory disorders. Despite advances in biologically targeted therapeutics for these diseases, glucocorticoid-induced osteoporosis (GIOP) remains the most common secondary form of osteoporosis. For patients with postmenopausal osteoporosis, the fracture risk rises slowly over the years after menopause. In contrast, an increased risk for fracture can be demonstrated as early as 3 months after commencing therapy with oral glucocorticoids.