Clinical studyClinical predictors of steroid-induced exacerbation in myasthenia gravis
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.
Section snippets
Subjects
This study was conducted using consecutive MG patients who visited Samsung Medical Center and Seoul Medical Center in Seoul, Korea, between March 1996 and June 2003. Patients were enrolled who were aged above 20 years, had grade II MG according to the Osserman classification,8 were being administered prednisone for the first time, and were hospitalized, so they could undergo serial neurologic examinations. We excluded patients with definite factors that would aggravate the clinical symptoms of
Comparison of clinical and laboratory findings
Twenty-three of 55 patients experienced prednisone-induced exacerbation as defined herein. Ten of these patients experienced such severe symptoms that they were admitted to the intensive care unit for approximately 10 days. Tracheostomy was performed for four patients, and long-term respiratory support was required. However, no deaths occurred because of exacerbations (Table 3).
The age of patients in the exacerbated group was significantly higher than that of patients in the non-exacerbated
Discussion
Currently, steroids are the mainstay of immunotherapy for MG. However, a well-designed, randomized, controlled trial proving the effectiveness of steroids for the treatment of MG has not been performed.10 The reported frequency of steroid-induced exacerbation varies between 25% and 75%;[7], [11], [12] but the definition of exacerbation in these studies was inconsistent, therefore comparisons between them are difficult. Recent hypotheses for the mechanisms by which worsening occurs are: the
Acknowledgement
We are indebted to Rene Cloer for assistance with preparation of the manuscript.
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