By: Jacqueline Chirico, PharmD Candidate c/o 2016
Myasthenia gravis is an autoimmune disorder in which an antibody-mediated attack is directed against the nicotinic acetylcholine (ACh) receptors at neuromuscular junctions.1 About 85% of people with myasthenia gravis have antibodies to the ACh receptor, while the remaining 15% are seronegative. Although one is more common than the other, both can have serious implications.2 The most recognizable sign of myasthenia gravis is skeletal muscle weakness that worsens during periods of activity and resolves after periods of rest. The muscles that control facial expressions, eye movements, talking, and swallowing may also be involved, as well as muscles that control breathing and neck movements.3
Myasthenia gravis may affect anywhere from 14 to 20 per 100,000 people. That is about 36,000- 60,000 cases in the United States; however, the disease is underdiagnosed and true prevalence is probably higher.4 It is not a hereditary disease, but it may have genetic susceptibility.2
Myasthenia gravis has a positive prognosis overall. Therapy can improve muscle weakness and result in relatively normal functioning. Some patients even go into remission after successful treatment.5 Treatment options include cholinesterase inhibitors, corticosteroids, and immunosupressants. Cholinesterase inhibitors improve muscle symptoms, while corticosteroids and immunosupressants reduce immune response by limiting antibody production.6 Prednisone is often used and is initiated at doses of 60-100 mg per day. A dose of 1 to 1.5 mg/kg may be used, however 100 mg/day is often recommended in adults. The dose can be modified to 100 mg every other day, after two to four weeks. This helps minimize side effects associated with prolonged corticosteroid use, but does not guarantee patients will be free from side effects or complications of therapy.7
Although often used, corticosteroids are associated with an increased risk of diabetes.8 Long-term corticosteroid use may alter glucose production and regulation, leading to hyperglycemia.9 Corticosteroids interfere with insulin signaling in skeletal muscle cells. This means that at high doses, patients, especially those with impaired glucose tolerance, are at an increased risk for steroid-induced diabetes.10
Despite the possibility of corticosteroid-induced hyperglycemia, there are not many studies done to investigate whether or not this interaction is clinically significant or whether corticosteroids should be avoided; however, it is clear which other drugs should be avoided in patients with myasthenia gravis.11
Every patient should be looked at individually, and there is always a risk versus benefit assessment that needs to be done before deciding whether or not to initiate a particular therapy.11 Drugs that have been proven to be associated with worsening myasthenia gravis that should be avoided are D-Penicillamine and Botulinum toxin.9,11
Some drugs with black box warnings associated with myasthenia gravis are the fluoroquinolone antibiotics and telithromycin.9,11 Some other antibiotics that should be used with caution in myasthenia gravis patients include azithromycin and the aminoglycosides.9,11 Additional drugs that should be used with caution are quinine, procainamide, magnesium, and even corticosteroids.9,11 While corticosteroids are used to treat myasthenia gravis, patients should be monitored for worsening of symptoms. The administration of vaccinations should be closely monitored in patients with myasthenia gravis, especially since a lot of treatments options are immunosuppressants.11
A systematic review from 2011 evaluated the frequency of multiple autoimmune diseases in myasthenia gravis. The review focused on 25 incidence studies and case series of all myasthenia gravis subtypes with information on other comorbid autoimmune diseases, such as diabetes and thyroid disorders.
After analysis of the reported frequencies of autoimmune diseases in myasthenia gravis, the pooled estimate showed a frequency of 13% (95% CI, 12-14%) in patients with myasthenia gravis.12 In other words, 13% of the 25 cases showed evidence of presence of another autoimmune disease. While the treatments that the patients were receiving were not recorded in this analysis, we know that treatments for autoimmune disorders commonly includes corticosteroids. Although diabetes was not the most common autoimmune disorder seen in these patients, there is a chance that it can develop as a secondary disorder in response to corticosteroid treatment of myasthenia gravis.
The strengths of this review include the fact that it is the first review that points to a correlation between myasthenia gravis and other autoimmune disorders. The methods used to pool the data across the different studies helped weaken the influence of variations that may have existed between the various study designs.12
While this review shows a possible correlation between autoimmune disorders and myasthenia gravis, there are some limitations. The basis for the review was evaluating published studies, so there was the chance of potential under-reporting or under-recognition of autoimmune diseases. As autoimmune disorders were not very well understood in the past, there may have been under-diagnosis of some of the disorders contained in this review. In addition, another limitation is the review’s inability to rule out any study where a patient could have developed a secondary autoimmune disorder due to being treated with an immunosuppressive agent.12
In conclusion, there is insufficient evidence to confirm or deny a definite relationship between the treatments for myasthenia gravis and diabetes. However, there is evidence that supports the avoidance or cautious use of certain medications in myasthenia gravis patients.12 In addition, it is unsafe to assume that myasthenia gravis led to the development of these autoimmune disorders. Of the many autoimmune disorders that were observed in the systematic review, diabetes wasn’t a common one. While there is a possibility that the connection between myasthenia gravis and diabetes can be linked to the fact that both are autoimmune diseases, there is a greater correlation between using immunosuppressants and corticosteroids to treat myasthenia gravis and the development of diabetes. This is because the effects of these classes of medications are better studied, and more information is readily available, than for the link between diabetes and myasthenia gravis, which isn’t well established in the literature.
- Drachman DB. Myasthenia gravis. N Engl J Med. 1994;330(25):1797-810.
- Muscular Dystrophy Association. What Causes Myasthenia Gravis (MG)? http://mda.org/disease/myasthenia-gravis/causes-inheritance. Accessed 03/14/15.
- National Institute of Health. What is Myasthenia Gravis? http://www.ninds.nih.gov/disorders/myasthenia_gravis/myasthenia_gravis.htm#What_is. Updated 03/12/15. Accessed 03/14/15.
- Myasthenia Gravis Foundation of America. Clinical Overview of MG. http://www.myasthenia.org/HealthProfessionals/ClinicalOverviewofMG.aspx#EPIDEMIOLOGY. Updated 06/2015. Accessed 07/30/15.
- National Institute of Neurological Disorders and Stroke. Myasthenia Gravis Facts Sheet: Prognosis. http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm#289523153. Published 09/2010. Updated 0727/15. Accessed 07/30/15.
- Mayo Clinic. Myasthenia gravis: Treatments and drugs. http://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/basics/treatment/con-20027124. Updated 04/23/13. Accessed 07/30/15.
- Medscape. Management of Myasthenia Gravis: Corticosteroids. http://www.medscape.com/viewarticle/4826953. Updated 2004. Accessed July 30, 2015.
- Yeh JH, Chen HJ, Lin CC, Chen YK, Chiu HC, Kao CH. Risk of diabetes mellitus among patients with myasthenia gravis. Acta Neurol Scand. 2015; [Epub ahead of print]. doi: 10.1111/ane.12374
- Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp Inc.: March 14, 2015.
- Rafacho A, Ortsäter H, Nadal A, Quesada I. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes. J Endocrinol. 2014;223(3):R49-62. doi: 10.1530/JOE-14-0373
- Drugs Associated with Worsening Myasthenia Gravis. Myasthenia Gravis Foundation of America. Available at: http://myasthenia.org/LinkClick.aspx?fileticket=zmLaFItarOQ=. Accessed 03/14/15.
- Mao ZF, Yang LX, Mo XA, et al. Frequency of autoimmune diseases in myasthenia gravis: a systematic review. Int J Neurosci. 2011;121(3):121-9. doi: 10.3109/00207454.2010.539307