FREQUENCY OF FAMILIAL OCCURRENCE AND ASSOCIATED AUTOIMMUNE DISEASES IN A COHORT OF PATIENTS WITH ACQUIRED AUTOIMMUNE MYASTHENIA GRAVIS FROM BELGRADE
Abstract
Introduction: Myasthenia gravis (MG) can be associated with other autoimmune diseases (AID), most frequently with Hashimoto’s thyroiditis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Familial occurrence (FOMG) is rare and it exists in 3.5-4.2% patients with MG.
Aim: To determine the occurrence of FOMG, the occurrence of AID associated with MG and to identify potential risk factors for developing MG in a cohort of patients from Belgrade.
Material and Methods: This study gathered data from 453 patient histories from the period 1992-2014 from the Clinic of Neurology, Clinical Center of Serbia. Three analyses were performed. The first measured the frequency of associated AID in patients with MG. In the second, patients who had MG associated with AID were compared to patients without associated AID. The third one included patients with FOMG and compared them with patients without FOMG. The demographic and clinical characteristics of these patients were analysed and comparisons were made between observed and control groups.
Results: The associated AID were present in 54 (11.9%) patients, the most frequent was Hashimoto thyreoiditis (4%), then SLE (1.3%), and RA, polymyositis and pernicious anaemia (0.9%). Patients with co-occurrence of MG and other AID were, in comparison with control group, more often female and the difference was on the border of statistical significance (p=0.056). They had late onset MG (LOMG) more frequently, a mild form of MG and positive anti-AChR antibodies, but these differences weren't statistically significant. FOMG was seen in 2.2% of patients. They had LOMG more frequently, were predominantly men, seropositive, and with mild form of the disease, but with no statistical significance compared to the control group.
Conclusion: In the Belgrade cohort, MG was often associated with other AID, while FOMG was relatively rare. There was no statistically significant difference in the observed clinical and demographic characteristics of analysed groups compared to control groups.
Key words: myasthenia gravis, familial occurrence, autoimmune diseasesReferences
Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015; 14(10):1023-36.
Nacu A, Andersen JB, Lisnic V, Owe JF, Gilhus NE. Complicating autoimmune diseases in myasthenia gravis: a review. Autoimmunity 2015; 48(6):362-368.
Hewagama A, Richardson B. The genetics and epigenetics of autoimmune diseases. J Autoimmun 2009; 33(1):3.
Wandstrat A, Wakeland E. The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nat Immunol 2001; 2(9):802-809.
Cardenas-Roldan J, Rojas-Villarraga A, Anaya JM. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC Med 2013; 11:73.
Foldes FF. Unusual familial occurrence of myasthenia gravis. JAMA 1960; 174(4):418-420.
Szobor A. Myasthenia gravis: familial occurrence. A study of 11000 myasthenia gravis patients. Acta Med Hung 1989; 46(1):13-21.
Salvado M, Canela M, Ponseti JM et al. Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort. Journal of the neurological sciences 2016; 360:110-114.
Thorlacius S, Aarli JA, Riise T, et al. Associated disorders in myasthenia gravis: autoimmune diseases and their relation to thymectomy. Acta neurologica scandinavica 1989; 80:290-295.
Osserman KE, Genkink G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 1971; 38:497-536.
Jaretzki A, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory board of the Myasthenia Gravis Foundation of America. Neurology 2000; 55:16-23.
Wang W, Chen YP, Wei DN. The clinical characteristics of early-onset versus late- onset types of myasthenia gravis. Zhonghua Nei Ke Za Zhi 2011; 50(6): 498-8.
Sanchez JL, Uribe CS, Franco AF, Jimenez ME, Arcos-Burgos OM, Palacio LG. Prevalence of myasthenia gravis in Antioquia, Colombia. Rev Neurol 2002; 34(11):1010-2.
Andersen JB, Heldal AT, Engeland A, Gilhus NE. Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries. Acta Neurol Scand Suppl 2014; 198:26-31.
Fang F, Sveinsson O, Thormar G, et al. The autoimmune spectrum of myasthenia gravis: a Swedish population-based study. J Intern Med 2015; 277(5):594-604.
Breiner A, Widdlifield J, Katzberg HD, Barnett C, Bril V, Tu K. Epidemiology of myasthenia gravis in Ontario, Canada. Neuromuscul Disord 2016; 26:41-6.
Poulas K, Tsibri E, Kokola A, et al. Epidemiology of seropositive myasthenia gravis in Greece. J Neurol Neurosurg Psychiatry 2001; 71(3):352-6.
Aragones JM, Altimiras J, Roura P, et al. Prevalence of myasthenia gravis in the Catalan county of Osona. Neurologia 2014.
Quintero OL, Amador-Patarroyo MJ, Montoya-Oritiz G, Rojas Villarraga A, Anaya JM. Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun 2012; 38:J109-19.
Le Panse R, Cizeron Clairac G, Cuvelier M, et al. Regulatory and pathogenic mechanisms in human autoimmune myasthenia gravis. Ann N Y Acad Sci 2008; 1132:135-42.
Zivkovic SA, Clemens PR, Lacomis D. Characteristics of late-onset myasthenia gravis. J Neurol 2012; 259:2167-71.
Christinsen P, Jensen BTS, Tsiropolous I, et al. Associated autoimmune diseases in myasthenia gravis. A population-based study. Acta Neurol Scand 1995; 91:192-195.
Mao ZF, Yang LX, Mo XA, et al. Int J Neurosci 2011; 357:2199-2200.
Kanazawa M, Shimohata T, Tanaka K, Nishizawa M. Clinical features of patients with myasthenia gravis associated with autoimmune diseases. Eur J Neurol 2007; 14:1403- 1404.
Jallouli M, Saadoun D, Eymard B, et al. The association of systemic lupus erythematosus and myasthenia gravis: a series of 17 cases, with a special focus on hydroxychloroquine use and a review of the literature. J Neurol 2012; 259:1290-1297.
Sthoeger Z, Neiman A, Elbirt D, et al. High prevalence of systemic lupus erythematosus in 78 myasthenia gravis patients: a clinical and serologic study. Am J Med Sci 2006; 331:4-9.
Blecher TE, Williams ER. Simultaneous myasthenia gravis and pernicious anaemia: A case report with organ antibody studies. Postgrad Med J 1967; 43(496):122-126.
Suzuki S, Utsugisawa K, Yoshikawa H, et al. Autoimmune targets of heart and skeletal muscles in myasthenia gravis. Arch Neurol 2009; 66:1334-1338.
Chang KH, Lyu RK, Ro LS, Wu YR, Chen CM. Coexistence of pernicious anemia and myasthenia gravis – a rare combination of autoimmune diseases in Taiwan. J Formos Med Assoc 2006; 105(11):946-949.
Chen YL, Yeh JH, Chiu HC. Clinical features of myasthenia gravis patients with autoimmune thyroid disease in Taiwan. Acta Neurol Scand 2013; 127(3):170-4.