A landmark study by an international group of researchers has highlighted that the risks of developing glucocorticoid-induced myopathy are higher than previously recognized and correlate strongly with cumulative steroid dosage.
The study, led by Dedee Murrell, MD DSC, Head of the Department of Dermatology at St George Hospital, University of New South Wales, Sydney, Australia, and Professorial Fellow at The George Institute for Global Health, followed an international cohort of patients with autoimmune blistering diseases of the skin.[1]
The multi-center study illuminates the high prevalence with which steroid myopathy is detected if carefully examined for and sheds light on risk factors for this complication of steroid use. Conducted between 2019 and 2023 across eight countries, the study analyzed data from 139 patients. Remarkably, nearly half (47.5%) of the participants developed some form of muscle weakness during the study period.
Autoimmune blistering diseases such as bullous pemphigoid and pemphigus vulgaris are chronic conditions that need long-term management strategies. A cornerstone of treatment for these conditions has been the use of systemic glucocorticoids, which, while effective, come with a significant risk of glucocorticoid-induced myopathy, as well as many other side effects.
Glucocorticoid-induced myopathy, first observed by Harvey Cushing MD in 1932, is a well-established side effect of glucocorticoid treatment. The onset of muscle weakness is usually painless, affecting the type IIb fast-twitch fibers in the shoulders and hips and making it hard for patients to raise their arms or to stand up from a sitting position. This weakness is particularly insidious for older patients, where loss of mobility can lead to significant comorbidities.
Study design
The researchers set out to investigate the prevalence of steroid-induced myopathy among autoimmune blistering disease patients and explored potential risk factors including dosage, treatment duration, sedentary lifestyle, age, ethnicity and gender.
The study enrolled 139 patients across a truly diverse ethnic and socio-economic landscape featuring blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States between February 2019 and July 2023.
There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period.
Unpacking the Risk Factors
The researchers used the Steritas GTI, part of the STOX Suite of clinical outcome assessments, to quantify steroid-toxicity over time. Higher GTI scores were associated with greater severity of myopathy, underscoring the importance of monitoring and managing steroid-toxicity.
The study identified several key risk factors associated with steroid-induced myopathy:
- Cumulative steroid dose: A higher cumulative dose correlated strongly with an increased risk of myopathy.
- Demographics: Older age, male gender and obesity significantly elevated the likelihood of developing myopathy.
Patients aged 50 to 65 were found to be about 2.4 times more likely to develop myopathy compared to those under 50. Men were twice as likely to develop this condition compared to women, and, having a body mass index (BMI) over 30 increased the risk of myopathy by 2.6 times compared to having a BMI below 24.9.
The strongest risk factor for the development of steroid myopathy, however, was cumulative dose. The risk of steroid myopathy increased consistently as the cumulative dose of prednisone rose from the lowest cumulative dose of 0.05-0.15 mg/kg/day to the highest of >0.75 mg/kg/day. This highest cumulative dose level was associated with an odds ratio of 36 for the development of steroid myopathy.
Mitigating the Risks
The study’s findings underscore the need for alternative treatments and strategies to mitigate the risks of myopathy. Recommendations include:
- Tapering steroids: reducing the cumulative dose to less than 0.75 mg/kg/day can significantly decrease the risk of developing steroid-induced myopathy.
- Exercise programs: implementing exercise regimens to combat muscle weakness.
Adjuvant or steroid-sparing therapies: exploring newer therapies that can minimize reliance on high-dose steroids.
Conclusion
While steroids remain a critical component in managing autoimmune blistering disease, their long-term use poses significant risks, particularly the development of steroid-induced myopathy. This study highlights the importance of careful monitoring and proactive management to balance disease control with the minimization of adverse effects.
“This is a really important paper that has investigated a very understudied side-effect of steroids. The correlation between cumulative dose and risk of steroid-induced myopathy is striking,“ commented John Stone, MD MPH, Professor of Medicine at Harvard Medical School, the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, and a co-author of the paper,
“While patients do improve on the reduction of steroid dosage, it takes (on average) 108 days for symptoms to improve. While a younger person may make a full recovery, if you're already 78 when you start taking steroids, and then you develop a profound steroid myopathy, it may take a lot longer than that to recover. I think that is generally underappreciated as a cause of cumulative morbidity associated with the disease and the steroids.”
References
- He A, Koszegi B, Uzun S, Bilgic A, Bozca BC, Yang B, Daneshpazhooh M, Boziou M, Patsatsi A, Kakuta R, Takahashi H, Nery D, Mundin C, Ramirez-Quizon M, Culton D, McAlpine S, Johal J, Shulruf B, Stone JH, Murrell DF. Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy. J Eur Acad Dermatol Venereol. 2024 May 31. doi: 10.1111/jdv.20149