Clinical predictors of steroid-induced exacerbation in myasthenia gravis

Abstract

Although oral corticosteroids are effective for the treatment of myasthenia gravis (MG), the possibility of steroid-induced exacerbation of symptoms, especially during the initial course of steroid therapy, has limited their use patients with severe MG. However, the factors influencing or predicting in exacerbation are not well understood. The purpose of this study was to identify the clinical factors that predict the initial paradoxical exacerbation of MG in response to steroid therapy. Fifty-five consecutive patients who were administered for the first time high doses of prednisone (40–80 mg) in a tertiary medical centre in Seoul, were included. Prednisone-induced exacerbation was defined as a significant reduction in a patient’s Myasthenia Gravis Severity Scale (MSS) score within 4 weeks of prednisone administration. We divided the patients into two groups on the basis of whether or not they experienced prednisone-induced exacerbation, and investigated the differences between the two groups with respect to clinical, laboratory and electrophysiological features. Twenty-three patients (42%) experienced definite exacerbation after prednisone therapy. Older age, predominantly severe bulbar symptoms, and low MSS score were found to be significant clinical predictors of exacerbation by multivariate logistic regression analysis. A high daily dosage of prednisone relative to body weight was found to be neither a predictor of exacerbation nor a predictor of early improvement in bivariate correlation analysis. Steroid-induced exacerbation in MG is a frequently encountered and challenging problem. Clinicians should be aware of the possibility of exacerbation of MG when prescribing prednisone, especially when treating elderly, bulbar dominant, or severely myasthenic patients.

Introduction

The first immunosuppressive agents used in the treatment of myasthenia gravis (MG) were corticosteroids. Prednisone is the most commonly used agent in the US[1], [2] and in our opinion also in Korea (in our opinion). Daily administration of high doses of prednisone frequently results in rapid improvement, often producing a remission of MG. However “paradoxical” exacerbation of MG by prednisone is also a well-known phenomenon, especially during the initial course of therapy.[3], [4], [5] The reported frequency of prednisone-induced exacerbation varies between 25% and 75%.[7], [11], [12] A wide range of severities of exacerbation have also been reported, varying between mild aggravation of weakness to death from respiratory failure.[6], [7]

Prednisone is usually used as a secondary agent in combination therapy for MG when symptoms cannot be adequately controlled with anti-cholinesterase agent monotherapy. Accordingly, it is likely that prednisone-induced exacerbation is a frequent problem for clinicians who prescribe prednisone for anti-cholinesterase-resistant MG. Thus, factors that provoke prednisone-induced exacerbation, and methods that can prevent or minimize prednisone-induced exacerbation are topics of great relevance to clinicians. However, until recently no published studies concerning MG have focused on these issues.

The current study was designed to determine the incidence and clinical features of prednisone-induced exacerbation. In addition, we aimed to comprehensively analyze the clinical predictors of prednisone-induced exacerbation, especially during the initial course of therapy.