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Journal of Neurology

, Volume 259, Issue 7, pp 1290–1297 | Cite as

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

  • M. Jallouli
  • D. Saadoun
  • B. Eymard
  • G. Leroux
  • J. Haroche
  • D. Le Thi Huong
  • C. De Gennes
  • C. Chapelon
  • O. Benveniste
  • B. Wechsler
  • P. Cacoub
  • Z. Amoura
  • J. C. Piette
  • N. Costedoat-Chalumeau
Original Communication

Abstract

The coexistence of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) is rarely reported, and most of the published studies are case reports. Hydroxychloroquine, an antimalarial agent, is an essential treatment in patients with SLE but special caution is recommended when used in MG patients. We retrospectively analyzed the clinical features, laboratory findings, and outcome of 17 patients with both diseases with a special focus regarding hydroxychloroquine use and with a review of the literature. All patients were women. The mean age at MG onset and SLE diagnosis was 34.5 [14–64] and 37.8 [18–72] years, respectively. The presenting symptoms of MG were limb weakness (94%), ocular (88%) and bulbar involvement (53%). Autoantibodies against the acetylcholine receptor were positive in 94% of cases. The main manifestations of SLE included arthritis (88%), cytopenias (53%) and skin rash (41%). Treatment of SLE required hydroxychloroquine (94%), steroids (47%) and immunosuppressive drugs (18%). Among eight patients (47%) who developed MG after initiation of hydroxychloroquine, the question of induction of MG by hydroxychloroquine was raised in one patient. On the other hand, an exacerbation of myasthenic symptoms was only seen in one of the eight patients who received hydroxychloroquine after the diagnosis of MG. Including our cases, we reviewed a total of 70 patients with SLE and MG. Compared with a large series of 1,000 unselected SLE patients, those with associated MG were older, had lower incidence of cutaneous, renal, and neurological manifestations, and higher frequency of anticardiolipin antibodies and lupus anticoagulant. In conclusion, the clinical pattern of patients with SLE and MG seems to be characterized by a less severe course of SLE and higher frequency of antiphospholipid antibodies. Hydroxychloroquine treatment appears to be safe in this setting.

Keywords

Systemic lupus erythematosus Myasthenia gravis Hydroxychloroquine Antiphospholipid Thymectomy 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Conti-Fine BM, Milani M, Kaminski HJ (2006) Myasthenia gravis: past, present, and future. J Clin Invest 116(11):2843–2854PubMedCrossRefGoogle Scholar
  2. 2.
    Park MJ, Kim YA, Lee SS, Kim BC, Kim MK, Cho KH (2004) Appearance of systemic lupus erythematosus in patients with myasthenia gravis following thymectomy: two case reports. J Korean Med Sci 19(1):134–136PubMedCrossRefGoogle Scholar
  3. 3.
    Costedoat-Chalumeau N, Amoura Z, Hulot JS, Lechat P, Piette JC (2007) Hydroxychloroquine in systemic lupus erythematosus. Lancet 369(9569):1257–1258PubMedCrossRefGoogle Scholar
  4. 4.
    Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725PubMedCrossRefGoogle Scholar
  5. 5.
    LM Miyakis S, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannapoulos PG, Kritis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemostasis 4(2):295–306CrossRefGoogle Scholar
  6. 6.
    Bouchez B, Arnott G, Delandsheer E, Courteville-Delamarre V (1983) Association of myasthenia and disseminated lupus erythematosus. Review of the literature apropos of a case. LARC Med 3(8):541–549PubMedGoogle Scholar
  7. 7.
    Isaacs P (1971) Myasthenia with systemic lupus and palmoplantar keratosis. Br Med J 4(5783):339–340PubMedCrossRefGoogle Scholar
  8. 8.
    MacKechnie HL, Squires AH, Platts M, Pruzanski W (1973) Thymoma, myasthenia gravis, erythroblastopenic anemia and systemic lupus erythematosus in one patient. Can Med Assoc J 109(8):733–738PubMedGoogle Scholar
  9. 9.
    Saint-Faust M, Perelman S, Dupont D, Velin P, Chatel M (2010) Transient neonatal myasthenia gravis revealing a myasthenia gravis and a systemic lupus erythematosus in the mother: case report and review of the literature. Am J Perinatol 27(2):107–110PubMedCrossRefGoogle Scholar
  10. 10.
    Gerli R, Paganelli R, Cossarizza A, Muscat C, Piccolo G, Barbieri D, Mariotti S, Monti D, Bistoni O, Raiola E, Venanzi FM, Bertotto A, Franceschi C (1999) Long-term immunologic effects of thymectomy in patients with myasthenia gravis. J Allergy Clin Immunol 103(5 Pt 1):865–872PubMedCrossRefGoogle Scholar
  11. 11.
    Aarli JA, Milde EJ, Thunold S (1975) Arthritis in myasthenia gravis. J Neurol Neurosurg Psychiatry 38(11):1048–1055PubMedCrossRefGoogle Scholar
  12. 12.
    Alarcon Segovia D, Galbraith RF, Maldonado JE, Howard FM Jr (1963) Systemic lupus erythematosus following thymectomy for myasthenia gravis. Report of two cases. Lancet 2(7309):662–665PubMedCrossRefGoogle Scholar
  13. 13.
    Denney D, Rose RL (1961) Myasthenia gravis followed by systemic lupus erythematosus. A case report. Neurology 11:710–713PubMedCrossRefGoogle Scholar
  14. 14.
    Kennes B, Delespesse G, Vandenbossche JL, Sternon J (1978) Systemic lupus erythematosus triggered by adult thymectomy in myasthenia gravis patient: report of a case. Acta Clin Belg 33(2):110–116PubMedGoogle Scholar
  15. 15.
    Laukaitis JP, Borenstein DG (1989) Multiple autoimmune diseases in a predisposed patient. Arthritis Rheum 32(1):119–120PubMedCrossRefGoogle Scholar
  16. 16.
    Mevorach D, Perrot S, Buchanan NM, Khamashta M, Laoussadi S, Hughes GR, Menkes CJ (1995) Appearance of systemic lupus erythematosus after thymectomy: four case reports and review of the literature. Lupus 4(1):33–37PubMedCrossRefGoogle Scholar
  17. 17.
    Schoenen J, Delwaide PJ (1976) The association of myasthenia and disseminated lupus erythematosus. 2 cases. Nouv Presse Med 5(18):1185–1188PubMedGoogle Scholar
  18. 18.
    Vaiopoulos G, Sfikakis PP, Kapsimali V, Boki K, Panayiotidis P, Aessopos A, Tsokos GC, Kaklamanis P (1994) The association of systemic lupus erythematosus and myasthenia gravis. Postgrad Med J 70(828):741–745PubMedCrossRefGoogle Scholar
  19. 19.
    Mizon JP, Morcamp D, Lefebvre P, Froissart M, Guidicelli CP, Goasguen J (1979) Associated myasthenia and disseminated lupus erythematosus. A report on two cases and complete review of the published literature (author’s transl). Ann Med Interne (Paris) 130(11):489–500Google Scholar
  20. 20.
    Abbruzzese G, Abbruzzese M, Bacigalupo A, Ratto S (1979) Systemic lupus erythematosus after thymectomy in a patient with myasthenia gravis. Neurology 29(10):1436–1437PubMedCrossRefGoogle Scholar
  21. 21.
    Calabrese LH, Bach JF, Currie T, Vidt D, Clough J, Krakauer RS (1981) Development of systemic lupus erythematosus after thymectomy for myasthenia gravis. Studies of suppressor cell function. Arch Intern Med 141(2):253–255PubMedCrossRefGoogle Scholar
  22. 22.
    Ciaccio M, Parodi A, Rebora A (1989) Myasthenia gravis and lupus erythematosus. Int J Dermatol 28(5):317–320PubMedCrossRefGoogle Scholar
  23. 23.
    Le Loet X, Pouyol F, Lees O, Ducastelle T, Godin M, Deshayes P (1986) Acute systemic lupus erythematosus after thymectomy for myasthenia. Sequential study of lymphocyte subpopulations. Rev Med Interne 7(4):425–432PubMedCrossRefGoogle Scholar
  24. 24.
    Sant SM (1997) Systemic lupus erythematosus after thymectomy in a patient with myasthenia gravis. Ir Med J 90(3):116–118PubMedGoogle Scholar
  25. 25.
    Tellez-Zenteno JF, Remes-Troche JM, Mimenza-Alvarado A, Garcia-Ramos G, Estanol B, Vega-Boada F (2003) The association of myasthenia gravis and connective tissue diseases. Effects of thymectomy in six cases with rheumatoid arthritis and one case with systemic lupus erythematosus. Neurologia 18(2):54–58PubMedGoogle Scholar
  26. 26.
    Omar HA, Alzahrani MA, Al Bshabshe AA, Assiri A, Shalaby M, Dwedar A, Abdulwahed SR, Hussein MR (2010) Systemic lupus erythematosus after thymectomy for myasthenia gravis: a case report and review of the literature. Clin Exp Nephrol 14(3):272–276Google Scholar
  27. 27.
    Lee H, Chen W, Su K, Chou C, Tsai C (2008) Myasthenia gravis associated with lupus nephritis. Lupus 17(9):860–861PubMedCrossRefGoogle Scholar
  28. 28.
    Iwadate H, Kobayashi H, Shio K, Noguchi E, Watanabe K, Sasajima T, Sekine H, Watanabe H, Ohira H, Obara K, Sato Y (2006) A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy. Mod Rheumatol 16(2):109–112PubMedCrossRefGoogle Scholar
  29. 29.
    Grinlinton FM, Lynch NM, Hart HH (1991) A pair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post-thymectomy. Arthritis Rheum 34(7):916–919PubMedCrossRefGoogle Scholar
  30. 30.
    Sthoeger Z, Neiman A, Elbirt D, Zinger H, Magen E, Burstein R, Eitan S, Abarbanel J, Mozes E (2006) High prevalence of systemic lupus erythematosus in 78 myasthenia gravis patients: a clinical and serologic study. Am J Med Sci 331(1):4–9PubMedCrossRefGoogle Scholar
  31. 31.
    Hrycek A (2009) A sequence of pathologic events in a patient after thymectomy for myasthenia gravis. Rheumatol Int [Epub ahead of print]Google Scholar
  32. 32.
    Meloni F, Gueli N, Villatico Campbell S, Di Maio F, Di Bernardo MG, Di Nuzzo M, Carmenini G (1996) A case of systemic lupus erythematosus (SLE) and myasthenia gravis (MG). Allergy 51(5):362–363PubMedGoogle Scholar
  33. 33.
    Branch CE Jr, Swift TR (1978) Systemic lupus erythematosus, myasthenia gravis, and Ehlers-Danlos syndrome. Ann Neurol 4(4):374–375PubMedCrossRefGoogle Scholar
  34. 34.
    Chan MK, Britton M (1980) Comparative clinical features in patients with myasthenia gravis with systemic lupus erythematosus. J Rheumatol 7(6):838–842PubMedGoogle Scholar
  35. 35.
    Killian PJ, Hoffman GS (1980) Coexistence of systemic lupus erythematosus and myasthenia gravis. South Med J 73(2):244–246PubMedCrossRefGoogle Scholar
  36. 36.
    Valesini G, Pastore R, de Berardinis PG, Serafini U, Vincent A, Bottazzo GN (1983) Appearance of anti-acetylcholine receptor antibodies coincident with onset of myasthenic weakness in patient with systemic lupus erythematosus. Lancet 1(8328):831PubMedCrossRefGoogle Scholar
  37. 37.
    Thorlacius S, Aarli JA, Riise T, Matre R, Johnsen HJ (1989) Associated disorders in myasthenia gravis: autoimmune diseases and their relation to thymectomy. Acta Neurol Scand 80(4):290–295PubMedCrossRefGoogle Scholar
  38. 38.
    Ben-Chetrit E, Pollack A, Flusser D, Rubinow A (1990) Coexistence of systemic lupus erythematosus and myasthenia gravis: two distinct populations of anti-DNA and anti-acetylcholine receptor antibodies. Clin Exp Rheumatol 8(1):71–74PubMedGoogle Scholar
  39. 39.
    Barbosa RE, Cordova S, Cajigas JC (2000) Coexistence of systemic lupus erythematosus and myasthenia gravis. Lupus 9(2):156–157PubMedCrossRefGoogle Scholar
  40. 40.
    Chaturvedi V, Handa R, Aggarwal P, Wali JP (2001) Systemic lupus erythematosus and myasthenia gravis. J Assoc Physicians India 49:670PubMedGoogle Scholar
  41. 41.
    Bhinder S, Majithia V, Harisdangkul V (2006) Myasthenia gravis and systemic lupus erythematosus: truly associated or coincidental-two case reports and review of the literature. Clin Rheumatol 25(4):555–556PubMedCrossRefGoogle Scholar
  42. 42.
    Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Domenech I, Aydintug AO, Jedryka-Goral A, de Ramon E et al (1993) Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European working party on systemic lupus erythematosus. Medicine (Baltimore) 72(2):113–124Google Scholar
  43. 43.
    Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8(5):475–490. pii:S1474-4422(09)70063-8PubMedCrossRefGoogle Scholar
  44. 44.
    Grob D, Brunner N, Namba T, Pagala M (2008) Lifetime course of myasthenia gravis. Muscle Nerve 37(2):141–149PubMedCrossRefGoogle Scholar
  45. 45.
    Mantegazza R, Baggi F, Antozzi C, Confalonieri P, Morandi L, Bernasconi P, Andreetta F, Simoncini O, Campanella A, Beghi E, Cornelio F (2003) Myasthenia gravis (MG): epidemiological data and prognostic factors. Ann NY Acad Sci 998:413–423PubMedCrossRefGoogle Scholar
  46. 46.
    Tsinzerling N, Lefvert AK, Matell G, Pirskanen-Matell R (2007) Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology. J Neurol Neurosurg Psychiatry 78(10):1109–1112PubMedCrossRefGoogle Scholar
  47. 47.
    Vincent A, Newsom-Davis J (1985) Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry 48(12):1246–1252PubMedCrossRefGoogle Scholar
  48. 48.
    Oh SJ (2009) Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. J Clin Neurol 5(2):53–64PubMedCrossRefGoogle Scholar
  49. 49.
    (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42(4):599–608Google Scholar
  50. 50.
    Manoussakis MN, Georgopoulou C, Zintzaras E, Spyropoulou M, Stavropoulou A, Skopouli FN, Moutsopoulos HM (2004) Sjogren’s syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjogren’s syndrome. Arthritis Rheum 50(3):882–891PubMedCrossRefGoogle Scholar
  51. 51.
    Xu D, Tian X, Zhang W, Zhang X, Liu B, Zhang F (2010) Sjogren’s syndrome-onset lupus patients have distinctive clinical manifestations and benign prognosis: a case-control study. Lupus 19(2):197–200PubMedCrossRefGoogle Scholar
  52. 52.
    Bagavant H, Thompson C, Ohno K, Setiady Y, Tung KS (2002) Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease. Int Immunol 14(12):1397–1406PubMedCrossRefGoogle Scholar
  53. 53.
    Bagavant H, Tung KS (2005) Failure of CD25+ T cells from lupus-prone mice to suppress lupus glomerulonephritis and sialoadenitis. J Immunol 175(2):944–950PubMedGoogle Scholar
  54. 54.
    Hang L, Theofilopoulos AN, Balderas RS, Francis SJ, Dixon FJ (1984) The effect of thymectomy on lupus-prone mice. J Immunol 132(4):1809–1813PubMedGoogle Scholar
  55. 55.
    Steinberg AD, Law LD, Talal N (1970) The role of NZB-NZW F1 thymus in experimental tolerance and auto-immunity. Arthritis Rheum 13(4):369–377PubMedCrossRefGoogle Scholar
  56. 56.
    Boonen A, Rennenberg R, van der Linden S (2000) Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature. Rheumatology (Oxford) 39(9):1044–1046CrossRefGoogle Scholar
  57. 57.
    Bozzolo E, Bellone M, Quaroni N, Voci C, Sabbadini MG (2000) Thymoma associated with systemic lupus erythematosus and immunologic abnormalities. Lupus 9(2):151–154PubMedCrossRefGoogle Scholar
  58. 58.
    Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin S (2005) Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 105(2):735–741PubMedCrossRefGoogle Scholar
  59. 59.
    Bonelli M, Smolen JS, Scheinecker C (2010) Treg and lupus. Ann Rheum Dis 69(Suppl 1):i65–i66PubMedCrossRefGoogle Scholar
  60. 60.
    Meraouna A, Cizeron-Clairac G, Panse RL, Bismuth J, Truffault F, Tallaksen C, Berrih-Aknin S (2006) The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis. Blood 108(2):432–440PubMedCrossRefGoogle Scholar
  61. 61.
    Schiffer L, Kumpers P, Davalos-Misslitz AM, Haubitz M, Haller H, Anders HJ, Witte T, Schiffer M (2009) B-cell-attracting chemokine CXCL13 as a marker of disease activity and renal involvement in systemic lupus erythematosus (SLE). Nephrol Dial Transplant 24(12):3708–3712PubMedCrossRefGoogle Scholar
  62. 62.
    Li LH, Li WX, Wu O, Zhang GQ, Pan HF, Li XP, Xu JH, Dai H, Ye DQ (2009) Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus: relation to the organ damage and lymphocytes apoptosis. Mol Biol Rep 36(8):2047–2052PubMedCrossRefGoogle Scholar
  63. 63.
    Moulian N, Bidault J, Truffault F, Yamamoto AM, Levasseur P, Berrih-Aknin S (1997) Thymocyte Fas expression is dysregulated in myasthenia gravis patients with anti-acetylcholine receptor antibody. Blood 89(9):3287–3295PubMedGoogle Scholar
  64. 64.
    Stein M, Bell MJ, Ang LC (2000) Hydroxychloroquine neuromyotoxicity. J Rheumatol 27(12):2927–2931PubMedGoogle Scholar
  65. 65.
    Robberecht W, Bednarik J, Bourgeois P, van Hees J, Carton H (1989) Myasthenic syndrome caused by direct effect of chloroquine on neuromuscular junction. Arch Neurol 46(4):464–468PubMedCrossRefGoogle Scholar
  66. 66.
    Sghirlanzoni A, Mantegazza R, Mora M, Pareyson D, Cornelio F (1988) Chloroquine myopathy and myasthenia-like syndrome. Muscle Nerve 11(2):114–119PubMedCrossRefGoogle Scholar
  67. 67.
    Ritenour RJ, Cruess AF, Mishra AV (2008) Chloroquine-related myasthenic syndrome with severe retinopathy. Can J Ophthalmol 43(2):241–243PubMedCrossRefGoogle Scholar
  68. 68.
    De Bleecker J, De Reuck J, Quatacker J, Meire F (1991) Persisting chloroquine-induced myasthenia? Acta Clin Belg 46(6):401–406PubMedGoogle Scholar
  69. 69.
    Pichon P, Soichot P, Loche D, Chapelon M (1984) Myasthenic syndrome induced by chloroquine poisoning: an unusual clinical form confirmed by ocular involvement. Bull Soc Ophtalmol Fr 84 (2):219–222, 225Google Scholar
  70. 70.
    Schumm F, Wietholter H, Fateh-Moghadam A (1981) Myasthenia syndrome during chloroquine treatment (author’s transl). Dtsch Med Wochenschr 106(51–52):1745–1747PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • M. Jallouli
    • 1
  • D. Saadoun
    • 1
  • B. Eymard
    • 2
  • G. Leroux
    • 1
  • J. Haroche
    • 1
  • D. Le Thi Huong
    • 1
  • C. De Gennes
    • 1
  • C. Chapelon
    • 1
  • O. Benveniste
    • 3
  • B. Wechsler
    • 1
  • P. Cacoub
    • 1
  • Z. Amoura
    • 1
  • J. C. Piette
    • 1
  • N. Costedoat-Chalumeau
    • 1
  1. 1.Service de Médecine Interne, Centre de référence national pour le Lupus Systémique et le syndrome des Antiphospholipides, Centre Hospitalier Universitaire Pitié-SalpêtrièreUniversité Paris 6, AP-HPParis Cedex 13France
  2. 2.Service de neurologie, AP-HP, Université Paris 6Paris Cedex 13France
  3. 3.Service de Médecine Interne 1, Centre Hospitalier Universitaire Pitié-SalpêtrièreUniversité Paris 6, AP-HPParis Cedex 13France

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