The Risk Benefit Ratio of Glucocorticoids in SLE: Have Things Changed over the Past 40 years?

Abstract

Purpose of review Glucocorticoids have been the mainstay of treatment in systemic lupus erythematosus for more than half a century. Despite advancements in knowledge concerning the pathophysiology of systemic lupus, the genomic/non-genomic actions of glucocorticoids, and the use of novel therapeutic agents in SLE, the burden of toxicity from glucocorticoid use remains unchanged. Recent findings SLE patients receiving long-term prednisone therapy are at significant risk of morbidity due to permanent organ damage and prednisone daily dosages above 6 mg have been shown to increase the risk of future organ damage by 50%. Glucocorticoid use carries a higher risk of opportunistic infections, iatrogenic osteoporosis and avascular necrosis, an increase in risk of cardiovascular events, cataracts and glaucoma, as well as psychiatric adverse effects like psychosis and manic episodes. There are limited data regarding the relative efficacy of the different glucocorticoid formulations or dosing regimens. Summary The use and dosing of glucocorticoids in SLE remains more art than science, although our knowledge regarding their complex genomic and non-genomic effects, as well as the resultant adverse effects, has greatly expanded over the past half a century.

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…[161][162][163][164] Various observational studies have indicated a protective effect of HCQ against serious infections in SLE. [165][166][167][168] In vitro studies have also suggested potential anti-viral effects of HCQ by means of increasing lysosomal pH and preventing post-translational modification of synthesized proteins that are crucial for replication and dissemination of viruses. 165,167,169 However, human studies have failed to identify any benefit of HCQ in preventing or managing viral infections, including dengue, chikungunya, and SARS-CoV-2.…”

“… 161 , 162 , 163 , 164 Various observational studies have indicated a protective effect of HCQ against serious infections in SLE. 165 , 166 , 167 , 168 . In vitro studies have also suggested potential anti-viral effects of HCQ by means of increasing lysosomal pH and preventing post-translational modification of synthesized proteins that are crucial for replication and dissemination of viruses.…”

Phytochemicals as Anti-Inflammatory Agents in Animal Models of Prevalent Inflammatory Diseases

“…However, current drugs have well known to have a wide array of adverse effects. Corticosteroids have severe side effects, although they can control the symptoms of serious lupus flare [ 31 ]. Oral prednisone for SLE therapy is currently used under 0.5 mg/kg dosage that is important to minimize total dosage to reduce steroid-induced toxicity [ 30 , 32 ].…”

Effects of glucocorticoids on the skin

“…After hormone binding, the receptors act as transcription factors. In this way, GCs produce either an increase or decrease in gene transcription (4,6) . The nongenomic effect of GCs may arise from hormone binding to receptors located on the cell membrane (8) , and the impact of GCs on lipids in the plasma membrane (9) .…”

“…Glucocorticoids are used in the treatment of many diseases, especially autoimmune disorders (3) , mainly based on their anti-inflammatory (4) , immunosuppressive and antiproliferative activity (5) . The main routes of administration of GCs are: oral, intravenous, intranasal, topical, inhaled, and intra-articular (6) . Prolonged exposure to excessive amounts of GCs leads to Cushing's syndrome.…”