Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.
Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular transmission, causing fatigue with generalized or localized weakness. With an annual incidence of 0.25 to 2 cases per 100,000 people, it is the most common disease involving the neuromuscular junction.1 Some complications of MG include myasthenic crisis, long-term medication-related side effects like opportunistic infections, and lymphoproliferative cancers. For better patient care and outcomes, a thorough understanding of the pathophysiologic mechanisms, clinical symptoms, treatment interventions, and complications in MG is required.2
Myasthenic crisis is a worsening of myasthenia that causes respiratory muscle paralysis and necessitates immediate respiratory support. Infection, high-dose steroid therapy, or insufficient treatment are the most common causes. Affected patients should be managed in the intensive care unit. Antibiotics, hydration management, and anticholinesterase medication are all necessary in addition to respiratory assistance. For immediate management of the condition, plasmapheresis or intravenous immunoglobulin treatment is required.3 Myasthenic crisis is a life-threatening illness that affects 10% to 20% of patients of MG.4 The median time from the onset of MG to the first myasthenic crisis varies from 8 to 12 months.1 The most common complication of myasthenic crisis is fever. Infectious complications include pneumonia, bronchitis, urinary tract infections, Clostridium difficile colitis, bacteremia, and sepsis. Patients admitted for myasthenic crisis are more prone to develop sepsis, deep vein thrombosis, and cardiac problems such as congestive heart failure, acute myocardial infarction, arrhythmias, and cardiac arrest than non-crisis MG patients. These complications, however, are not independent predictors of death.1
Thymoma Myasthenia Gravis
Myasthenia gravis is a neuromuscular junction disorder induced by acetylcholine receptor (AChR) antibodies in 85% of cases. Antibodies to titin and ryanodine receptors (RyR) are present in 95% of thymoma MG cases and 50% of late-onset MG cases, and they are linked to severe disease and thus considered predictors of thymoma MG outcomes.5 Thymoma MG accounts for roughly 15% of all MG cases, and its pathogenesis involves a humoral immune response to an epitope on thymoma cells that is similar to the epitope on neuromuscular junction components. The T lymphocytes around the neoplastic thymoma cells express epitopes that cross-react with AChRs. AChR antibodies are found in the serum of all patients with thymoma MG. AChR antibodies affect the neuromuscular junction, causing muscle weakness by targeting the nicotinic AChR at the endplate region of the postsynaptic membrane.6 Patients with thymoma MG are more likely to develop blood cytopenias, hypogammaglobulinemia, polymyositis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M component, and skin changes), neuromyotonia, and autoimmune encephalitis, which are otherwise uncommon in MG patients.7
Neuromyelitis optica with aquaporin-4 antibodies has a prevalence of 40 cases per million people, is strongly linked with MG, and can develop before or after the onset of disease. Patients with MG develop amyotrophic lateral sclerosis (ALS) at a higher rate than members of the general population. Autoimmune disease is a risk factor for ALS in general, but the link with MG is particularly significant.7
Myocarditis is uncommon, however, it occurs more frequently in patients with MG. Myasthenia-related clinical cardiac disease and heart dysfunction, on the other hand, are extremely uncommon. Myasthenia gravis has not been linked to an increase in heart disease-related mortality in population-based studies.7
Long-term steroid complications including osteoporosis, hyperglycemia, cataracts, weight gain, hypertension, and avascular necrosis of the hip are possible consequences of MG treatment. With prolonged immunosuppressive medication, there is also a risk of lymphoproliferative cancers and opportunistic infections such as systemic fungal infections, tuberculosis, and Pneumocystis carinii pneumonia.2 Extrathymic malignancies exacerbated by MG have been documented in a number of cases, which are referred to as paraneoplastic syndromes. Lung cancer is the most common extrathymic malignancy. The medical literature only contains one description of MG as a paraneoplastic condition linked to renal cell carcinoma.8
Patients with early-onset MG and thymic hyperplasia are more likely to have a second autoimmune disease, which occurs in about 15% of patients. Thyroiditis is the most common comorbid condition, followed by systemic lupus erythematosus and rheumatoid arthritis. Thyroid disease is very common in patients with ocular myasthenia.7
- Wendell LC, Levine JM. Myasthenic crisis. Neurohospitalist. 2011;1(1):16-22. doi:10.1177/1941875210382918
- Beloor Suresh A, Asuncion RMD. Myasthenia gravis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021.
- Thanvi BR, Lo TCN. Update on myasthenia gravis. Postgrad Med J. 2004;80(950):690-700. doi:10.1136/pgmj.2004.018903
- Huang Y, Tan Y, Shi J, Li K, Yan J, Guan Y. Patients with myasthenia gravis with acute onset of dyspnea: predictors of progression to myasthenic crisis and prognosis. Front Neurol. 2021;12:767961. doi:10.3389/fneur.2021.767961
- Romi F. Thymoma in myasthenia gravis: from diagnosis to treatment. Autoimmune Dis. 2011;2011:474512. doi:10.4061/2011/474512
- Kumar R. Myasthenia gravis and thymic neoplasms: a brief review. World J Clin Cases. 2015;3(12):980-983. doi:10.12998/wjcc.v3.i12.980
- Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375(26):2570-2581. doi:10.1056/NEJMra1602678
- Zheng Y, Luo J, Jin H, Liu R, Hao H, Gao F. Myasthenia gravis associated with renal cell carcinoma: a paraneoplastic syndrome or just a coincidence. BMC Neurol. 2021;21(1):277. doi:10.1186/s12883-021-02311-8
Reviewed by Hasan Avcu, MD, on 2/20/2022.