i002 Between Scylla and Charybdis: the toxicity of glucocorticoids in rheumatic disease

Abstract

Inflammation plays a central role in the pathogenesis of many rheumatic diseases. In 1948 the first patient with rheumatoid arthritis was treated with cortisone, producing dramatic benefit. However, it rapidly became evident that long-term use of glucocorticoids led to what we now call a Cushingoid phenotype (central obesity, muscle wasting, skin fragility, impaired healing), accompanied by less visible toxicities such as diabetes, hypertension, bone fragility and iatrogenic adrenal suppression. Despite this, synthetic glucocorticoids are still used widely for the treatment of inflammatory rheumatic diseases, for example as a component of treat-to-target algorithms aiming for remission or minimal disease activity. At the same time, we are now dealing with an ageing population with multimorbidity, introducing additional complexities into treatment choices. Clinicians making decisions about glucocorticoid prescribing need to weigh up the risks of treatment against the likely consequences of uncontrolled inflammatory disease. This lecture will review recent data regarding measurement of the overall impact of glucocorticoid therapy and estimation of the risks of key glucocorticoid-related adverse effects. Biological mechanisms influencing the interplay of ageing, inflammatory disease and glucocorticoid therapy will be discussed. In Homer's epic poem The Odyssey, Odysseus was forced to choose between taking his ship past Scylla, a six-headed sea monster, and Charybdis, a whirlpool. The cunning Odysseus chose Scylla, which would almost certainly lose him a few of his crew, rather than Charybdis which might sink the entire ship. Like Odysseus, the clinician is faced with difficult choices about long-term glucocorticoid prescribing. Better knowledge of the risks associated with each treatment option will help inform those choices for optimal patient outcomes.