Myasthenia gravis (MG) is a chronic, rare, autoimmune disease in which the body’s own immune system attacks components of the neuromuscular junction, disrupting the transmission of signals from nerve to muscle. Myasthenia gravis manifests as weakness and fatigue in voluntary skeletal muscles, particularly those of the eyes, throat, face, jaw, and limbs.1 

Incidence

In 55 studies conducted from 1950 to 2007, the incidence rate of MG varied between 1.7 and 21.3, resulting in a global pooled incidence rate of 5.3 per 1,000,000 persons per year.2 Another 29 studies between 2007 and 2019 reported an incidence rate of MG ranging from 0.15 to 61.33 per 1,000,000 persons per year.3 A 2021 study cites the incidence rate of MG as 4.1 to 30 cases per 1,000,000 persons per year.4

Prevalence

The reported prevalence of MG over the past 50 years is increasing and varies based on location.1,2,5 Global prevalence rates range from 150 to 200 cases per 1,000,000 people.4

The prevalence of MG in the United States is estimated at 14 to 20 cases per every 100,000 people or between 36,000 and 60,000 cases.1,5,6 In Europe, an estimated 56,000 to 123,000 individuals live with MG.3 

Race

Specific ethnic backgrounds may factor into MG onset, presentation, and disease progression. White patients demonstrate a higher age of onset than other races by approximately 17.3 years.7

Black women demonstrated a higher incidence of MG at 0.01 per 1000 persons per year compared to white patients and black men, who have an estimated incidence of 0.007 to 0.009 per 1000 persons per year.8 

Black patients are more likely to develop treatment-resistant ocular MG than white patients, who show higher probabilities of developing more severe forms of generalized MG which often respond poorly to treatment.9

Overall, there is a lower incidence and prevalence among individuals of Asian descent.4 However, Asian populations demonstrate a higher incidence of early-onset ocular MG, including juvenile-onset and infantile-onset. Approximately 80.6% of Asian patients with infantile-onset MG develop ocular MG, compared with 14% to 30% of patients with infantile-onset MG in Europe and North America.10 An estimated 10% to 15% of MG cases in white individuals represent juvenile-onset MG, while up to 50% of MG cases in Asian individuals are juvenile-onset, particularly in the southern Chinese population.11

Sex

Women are more affected by MG than men, with a 3:1 sex ratio prior to 40 years of age. However, as the population ages, men are increasingly more affected after age 50, resulting in closer to a 1:1 sex ratio for onset at older ages.1,2,4 Scientists hypothesize that stress, viral infections, pregnancy, and childbirth trigger the development of MG, contributing to the middle-age sex disparities.2

Age

While women most commonly manifest MG symptoms in their 20s and 30s, men are more commonly diagnosed in their 70s and 80s.1 Researchers calculated a 99.6% probability that the mean difference in age between the sexes at MG diagnosis was greater than 10 years.7

The most common age of MG onset ranges from 20 to 40 years of age, with women accounting for 60% of these patients.5 Nonwhite patients typically develop MG at an earlier age.7

Subtype

The most prevalent subtype of MG is the anti-acetylcholine receptor (AChR) subtype. Anti-AChR antibodies are detected in 85% to 95% of patients with generalized MG, while they are present in 40% to 70% of patients with ocular MG.12 

The second most prevalent subtype is the muscle-specific tyrosine kinase (MuSK) subtype. Anti-MuSK antibodies are detected in 7% to 10% of all patients with MG and up to 40% of patients who test negative for anti-AChR antibodies. Women are more likely to develop MuSK-positive MG, accounting for 85% of MuSK MG cases.4

Lipoprotein receptor-related protein 4 (LRP4) accounts for 2% to 50% of double seronegative MG cases, while up to 10% of patients with MG characteristics exhibit no identifiable autoantibodies.4,13 

References

  1. Howard JF. Clinical overview of MG. Myasthenia Gravis Foundation of America. Accessed February 7, 2022.
  2. Carr AS, Cardwell CR, McCarron PO, McConville J. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;10:46. doi:10.1186/1471-2377-10-46
  3. Bubuioc AM, Kudebayeva A, Turuspekova S, Lisnic V, Leone MA. The epidemiology of myasthenia gravis. J Med Life. 2021;14(1):7-16. doi:10.25122/jml-2020-0145
  4. Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations. J Clin Med. 2021;10(11):2235. doi:10.3390/jcm10112235
  5. Pekmezović T, Lavrnić D, Jarebinski M, Apostolski S. [Epidemiology of myasthenia gravis]. Srp Arh Celok Lek. 2006;134(9-10):453-456. Serbian.
  6. Phillips LH II. The epidemiology of myasthenia gravis. Ann N Y Acad Sci. 2003;998:407-412. doi:10.1196/annals.1254.053
  7. Peragallo JH, Bitrian E, Kupersmith MJ, et al. Relationship between age, gender, and race in patients presenting with myasthenia gravis with only ocular manifestations. J Neuroophthalmol. 2016;36(1):29-32. doi:10.1097/WNO.0000000000000276
  8. Alshekhlee A, Miles JD, Katirji B, Preston DC, Kaminski HJ. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology. 2009;72(18):1548-1554. doi:10.1212/WNL.0b013e3181a41211
  9. Heckmann JM, Owen EP, Little F. Myasthenia gravis in South Africans: racial differences in clinical manifestations. Neuromuscul Disord. 2007;17(11-12):929-934. doi:10.1016/j.nmd.2007.07.002
  10. Murai H, Yamashita N, Watanabe M, et al. Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey. J Neurol Sci. 2011;305(1-2):97-102. doi:10.1016/j.jns.2011.03.004
  11. Huang X, Li Y, Feng H, Chen P, Liu W. Clinical characteristics of juvenile myasthenia gravis in southern China. Front Neurol. 2018;9:77. doi:10.3389/fneur.2018.00077
  12. Pakzad Z, Aziz T, Oger J. Increasing incidence of myasthenia gravis among elderly in British Columbia, Canada. Neurology. 2011;76(17):1526-1528. doi:10.1212/WNL.0b013e318217e735
  13. Lazaridis K, Tzartos SJ. Autoantibody specificities in myasthenia gravis; implications for improved diagnostics and therapeutics. Front Immunol. 2020;11:212. doi:10.3389/fimmu.2020.00212

Reviewed by Kyle Habet, MD, on 2/14/2022.