Skip to main content

Advertisement

Log in

Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its’ severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

The data presented in this report will be made available to bona fide investigators upon request to the corresponding author.

Code availability

Not applicable.

References

  1. Silvestri NJ, Wolfe GI (2012) Myasthenia gravis. Semin Neurol 32(3):215–226

    Article  PubMed  Google Scholar 

  2. Gilhus NE (2016) Myasthenia gravis. N Engl J Med 375(26):2570–2581

    Article  CAS  PubMed  Google Scholar 

  3. Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14(10):1023–1036

    Article  CAS  PubMed  Google Scholar 

  4. Binks S, Vincent A, Palace J (2016) Myasthenia gravis: a clinical-immunological update. J Neurol 263(4):826–834

    Article  CAS  PubMed  Google Scholar 

  5. Zisimopoulou P, Evangelakou P, Tzartos J, Lazaridis K, Zouvelou V, Mantegazza R et al (2014) A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun 52:139–145

    Article  CAS  PubMed  Google Scholar 

  6. Argov Z (2011) Current approach to seronegative myasthenia. J Neurol 258(1):14–18

    Article  PubMed  Google Scholar 

  7. Huda S, Koneczny I, Jacobsen L, Beeson D, Vincent A (2014) Seronegative myasthenia gravis-clinical/serological aspects. J Neurol Neurosur Psychiatry 85(10):e4

    Article  Google Scholar 

  8. Vernino S (2015) Unraveling the enigma of seronegative myasthenia gravis. JAMA Neurol 72(6):630–631

    Article  PubMed  Google Scholar 

  9. Richman DP, Agius MA (2003) Treatment of autoimmune myasthenia gravis. Neurology 61(12):1652–1661

    Article  CAS  PubMed  Google Scholar 

  10. Gold R, Hohlfeld R, Toyka KV (2008) Progress in the treatment of myasthenia gravis. Ther Adv Neurol Disord 1(2):36–51

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gotterer L, Li Y (2016) Maintenance immunosuppression in myasthenia gravis. J Neurol Sci 369:294–302

    Article  PubMed  Google Scholar 

  12. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J (2019) Myasthenia gravis. Nat Rev Dis Primers 5(1):30

    Article  PubMed  Google Scholar 

  13. Gilhus NE, Owe JF, Hoff JM, Romi F, Skeie GO, Aarli JA (2011) Myasthenia gravis: a review of available treatment approaches. Autoimmune Dis 2011:847393

    PubMed  PubMed Central  Google Scholar 

  14. Torda C, Wolff HG (1944) Effect of adrenotrophic hormone of pituitary gland on ability of tissue to synthesize acetylcholine. Proc Soc Exp Biol Med 57(1):137–139

    Article  Google Scholar 

  15. Torda C, WOLFF HG, (1951) Effects of administration of the adrenocorticotropic hormone (ACTH) on patients with myasthenia gravis. AMA Arch Neurol Psychiatry 66(2):163–170

    Article  CAS  PubMed  Google Scholar 

  16. Millikan CH, Eaton LM (1951) Clinical evaluation of ACTH and cortisone in myasthenia gravis. Neurology 1(3):145

    Article  CAS  PubMed  Google Scholar 

  17. Grob D, Harvey A (1952) Effect of adrenocorticotropic hormone (ACTH) and cortisone administration in patients with myasthenia gravis and report of onset of myasthenia gravis during prolonged cortisone administration. Bull Johns Hopkins Hosp 91(2):124

    CAS  PubMed  Google Scholar 

  18. Schlezinger N (1952) Present status of therapy in myasthenia gravis. J Am Med Assoc 148(7):508–513

    Article  CAS  PubMed  Google Scholar 

  19. Namba T, Brunner NG, Shapiro MS, Grob D (1971) Corticotropin therapy in myasthenia gravis: effects, indications, and limitations. Neurology 21(10):1008–1018

    Article  CAS  PubMed  Google Scholar 

  20. Millikan CH, Eaton LM (1950) Clinical evaluation of the effect of adrenocorticotrophic hormone and cortisone on myasthenia gravis. J Lab Clin Med 36(6):966–967

    CAS  PubMed  Google Scholar 

  21. Mc ED (1951) Diseases and disorders of muscle function. Bull N Y Acad Med 27(1):3–23

    Google Scholar 

  22. Shy GM, Brendler S, Rabinovitch R, Mc ED (1950) Effects of cortisone in certain neuromuscular disorders. J Am Med Assoc 144(16):1353–1358

    Article  CAS  PubMed  Google Scholar 

  23. Schneider-Gold C, Gajdos P, Toyka KV, Hohlfeld RR (2005) Corticosteroids for myasthenia gravis. Cochrane Database Syst Rev 2:1

    Google Scholar 

  24. Warmolts JR, Engel WK (1972) Benefit from alternate-day prednisone in myasthenia gravis. N Engl J Med 286(1):17–20

    Article  CAS  PubMed  Google Scholar 

  25. Engel WK, Warmolts JR (1971) Myasthenia gravis: a new hypothesis of the pathogenesis and a new form of treatment. Ann N Y Acad Sci 183:72–87

    Article  CAS  PubMed  Google Scholar 

  26. Warmolts JR, Engel WK, Whitaker JN (1970) Alternate-dy prednisone in a patient with myasthenia gravis. Lancet 2(7684):1198–1199

    Article  CAS  PubMed  Google Scholar 

  27. Seybold ME, Drachman DB (1974) Gradually increasing doses of prednisone in myasthenia gravis. Reducing the hazards of treatment. N Engl J Med 290(2):81–84

    Article  CAS  PubMed  Google Scholar 

  28. Sghirlanzoni A, Peluchetti D, Mantegazza R, Fiacchino F, Cornelio F (1984) Myasthenia gravis: prolonged treatment with steroids. Neurology 34(2):170–174

    Article  CAS  PubMed  Google Scholar 

  29. Jenkins RB (1972) Treatment of myasthenia gravis with prednisone. Lancet 1(7754):765–767

    Article  CAS  PubMed  Google Scholar 

  30. Pinelli P, Tonali P, Scoppetta C (1974) Long-term treatment of myasthenia gravis with alternate-day prednisone. Report on 15 patients. Eur Neurol 12(3):129–141

    Article  CAS  PubMed  Google Scholar 

  31. McQuillen MP (1974) Letter: prednisone schedule for myasthenia gravis. N Engl J Med 290(11):631–632

    CAS  PubMed  Google Scholar 

  32. Evoli A, Batocchi AP, Palmisani MT, Lo Monaco M, Tonali P (1992) Long-term results of corticosteroid therapy in patients with myasthenia gravis. Eur Neurol 32(1):37–43

    Article  CAS  PubMed  Google Scholar 

  33. Pascuzzi RM, Coslett HB, Johns TR (1984) Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol 15(3):291–298

    Article  CAS  PubMed  Google Scholar 

  34. Nagane Y, Suzuki S, Suzuki N, Utsugisawa K (2011) Early aggressive treatment strategy against myasthenia gravis. Eur Neurol 65(1):16–22

    Article  PubMed  Google Scholar 

  35. Utsugisawa K, Nagane Y, Akaishi T, Suzuki Y, Imai T, Tsuda E et al (2017) Early fast-acting treatment strategy against generalized myasthenia gravis. Muscle Nerve 55(6):794–801

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bedlack RS, Sanders DB (2002) Steroid treatment for myasthenia gravis: steroids have an important role. Muscle Nerve 25(1):117–121

    Article  PubMed  Google Scholar 

  37. Rowland LP (1980) Controversies about the treatment of myasthenia gravis. J Neurol Neurosurg Psychiatry 43(7):644–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mann J, Johns T, Campa J, Muller W (1976) Long-term prednisone followed by thymectomy in myasthenia gravis. Ann N Y Acad Sci 274:608–622

    Article  CAS  PubMed  Google Scholar 

  39. Fischer KC, Schwartzman RJ (1974) Oral corticosteroids in the treatment of ocular myasthenia gravis. Neurology 24(8):795

    Article  CAS  PubMed  Google Scholar 

  40. Kanai T, Uzawa A, Kawaguchi N, Oda F, Ozawa Y, Himuro K et al (2019) Predictive score for oral corticosteroid-induced initial worsening of seropositive generalized myasthenia gravis. J Neurol Sci 396:8–11

    Article  CAS  PubMed  Google Scholar 

  41. Scoppetta C, Tonali P, Evoli A, David P, Crucitti F, Vaccario M (1979) Treatment of myasthenia gravis. J Neurol 222(1):11–21

    Article  CAS  PubMed  Google Scholar 

  42. Johns T (1977) Treatment of myasthenia gravis: long-term administration of corticosteroids with remarks on thymectomy. Adv Neurol 17:99–122

    CAS  PubMed  Google Scholar 

  43. Howard JF, Duane DD, Lambert EH, Daube JR (1976) Alternate-day prednisone: preliminary report of a double-blind controlled study. Ann N Y Acad Sci 274:596–607

    Article  PubMed  Google Scholar 

  44. Bae JS, Go SM, Kim BJ (2006) Clinical predictors of steroid-induced exacerbation in myasthenia gravis. J Clin Neurosci 13(10):1006–1010

    Article  CAS  PubMed  Google Scholar 

  45. Kjær M (1971) Myasthenia gravis and myasthenic syndromes treated with prednisone. Acta Neurol Scand 47(4):464–474

    Article  PubMed  Google Scholar 

  46. Brunner NG, Namba T, Grob D (1972) Corticosteroids in management of severe, generalized myasthenia gravis: effectiveness and comparison with corticotropin therapy. Neurology 22(6):603

    Article  CAS  PubMed  Google Scholar 

  47. Arsura E, Brunner NG, Namba T, Grob D (1985) High-dose intravenous methylprednisolone in myasthenia gravis. Arch Neurol 42(12):1149–1153

    Article  CAS  PubMed  Google Scholar 

  48. Ozawa Y, Uzawa A, Kanai T, Oda F, Yasuda M, Kawaguchi N et al (2019) Efficacy of high-dose intravenous methylprednisolone therapy for ocular myasthenia gravis. J Neurol Sci 402:12–15

    Article  CAS  PubMed  Google Scholar 

  49. Komiyama A, Arai H, Kijima M, Hirayama K (2000) Extraocular muscle responses to high dose intravenous methylprednisolone in myasthenia gravis. J Neurol Neurosurg Psychiatry 68(2):214–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sugimoto T, Ochi K, Ishikawa R, Tazuma T, Hayashi M, Mine N et al (2020) Initial deterioration and intravenous methylprednisolone therapy in patients with myasthenia gravis. J Neurol Sci 412:116740

    Article  CAS  PubMed  Google Scholar 

  51. Lindberg C, Andersen O, Lefvert A (1998) Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. Acta Neurol Scand 97(6):370–373

    Article  CAS  PubMed  Google Scholar 

  52. Osserman K (1958) Myasthenia gravis. Grune & Stratton. Inc, New York

    Google Scholar 

  53. Osserman KE, Genkins G (1971) Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 38(6):497–537

    CAS  PubMed  Google Scholar 

  54. Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS et al (2000) Myasthenia gravis: recommendations for clinical research standards. Neurology 55(1):16–23

    Article  PubMed  Google Scholar 

  55. Oosterhuis H (1984) Myasthenia gravis. Clinical neurology and neurosurgery monographs. Churchill Livingstone, Edinburgh, pp 45–50

    Google Scholar 

  56. Besinger UA, Toyka KV, Hömberg M, Heininger K, Hohlfeld R, Fateh-Moghadam A (1983) Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity. Neurology. 33(10):1316

    Article  CAS  PubMed  Google Scholar 

  57. Dalby A, Kjar M, De Fine Olivarius B (1973) Continuous treatment of myasthenia gravis with prednisone. Myasthenia Gravis. Papers. pp. 164

Download references

Funding

This work did not receive any fundings.

Author information

Authors and Affiliations

Authors

Contributions

IL and IS contributed to the study conception and design. Material preparation, data collection and analysis were performed by IL and IS. The first draft of the manuscript was written by IL and IS. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Itay Lotan.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lotan, I., Hellmann, M.A., Wilf-Yarkoni, A. et al. Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review. J Neurol 268, 4573–4586 (2021). https://doi.org/10.1007/s00415-020-10264-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-10264-0

Keywords

Navigation