Investigating the Occurrence of Femoral Head Avascular Necrosis in Patient with Multiple Sclerosis Treated with Interferon-Beta

Document Type : Original Article (s)

Authors

1 Student of Medicine, Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Multiple sclerosis (MS) is a demyelinating inflammatory disease of central nervous system. Avascular necrosis (AVN) of femoral head is reported as an unusual complaint of multiple sclerosis. In this study, occurrence of AVN due to use of interferon-beta remedies was assessed.Methods: This was a descriptive cross-sectional study on 6420 cases with relapsing-remitting multiple sclerosis from 2007 to 2017. Recorded information were based on the assessment by expert neurologist, and included demographics, time of disease onset, time of the diagnosis of avascular necrosis (AVN), unilateral or bilateral necrosis, duration and dosage and type of beta-interferon, dosage of oral corticosteroid, and pulse of corticosteroid therapy. The data were analyzed, and descriptive information was expressed as mean, standard deviation, and percentage.Findings: In this study, 6420 patients with history of relapsing-remitting multiple sclerosis were evaluated. Of them, 4900 cases were treated with interferon-beta which included in the study. Eight patients presented avascular necrosis of femoral head. Mean age of patients was 30.25 ± 10.09 years. 75% of 4900 cases were treated with interferon-beta were women. Mean duration between multiple sclerosis onset and presentation of avascular necrosis was 42.12 ± 28.47 months. 62.5% of patients had unilateral avascular necrosis. 87.5% of cases were under treatment with interferon-beta-1a and the rest 12.5% treated with interferon-beta-1b.Conclusion: Based on the findings of our study, it is possible to hypothesize that use of interferon-beta may have an effect on occurrence of avascular necrosis among patients with multiple sclerosis. The probable mechanisms could be angiogenesis inhibition, vasoconstriction, and small thrombosis formation in arterioles, as well as leukocytoclastic vasculitis. Further studies are recommended.

Keywords


  1. Wicaksono AR, Yudiyanta. Avascular necrosis of femoral head as a complication of corticosteroid therapy in multiple sclerosis patient: A case report. J Neurol Sci. 2017; 381: 1067.
  2. Baumhackl U. The search for a balance between short and long-term treatment outcomes in multiple sclerosis. J Neurol 2008; 255(1): 75-83.
  3. Taylor KL, Leaman DW, Grane R, Mechti N, Borden EC, Lindner DJ. Identification of interferon-beta-stimulated genes that inhibit angiogenesis in vitro. J Interferon Cytokine Res 2008; 28(12): 733-40.
  4. Smith DW. Is avascular necrosis of the femoral head the result of inhibition of angiogenesis? Med Hypotheses 1997; 49(6): 497-500.
  5. Yong VW, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis: Mechanisms of action. Neurology 1998; 51(3): 682-9.
  6. Haghikia A, Faissner S, Pappas D, Pula B, Akkad DA, Arning L, et al. Interferon-beta affects mitochondrial activity in CD4+ lymphocytes: Implications for mechanism of action in multiple sclerosis. Mult Scler 2015; 21(10): 1262-70.
  7. Yang CH, Chen CH, Chan HL. Skin necrosis following a recombinant interferon-beta-1b injection. Chang Gung Med J 2002; 25(11): 774-7.
  8. Ozuguz P, Kacar SD, Karaca S, Tokyol C. A case of septal panniculitis secondary to interferon treatment. Cutan Ocul Toxicol 2014; 33(4): 351-2.
  9. Faghihi G, Basiri A, Pourazizi M, Abtahi-Naeini B, Saffaei A. Multiple cutaneous necrotic lesions associated with Interferon beta-1b injection for multiple sclerosis treatment: A case report and literature review. J Res Pharm Pract 2015; 4(2): 99-103.
  10. Smets I, Van Deun L, Bohyn C, van Pesch V, Vanopdenbosch L, Dive D, et al. Corticosteroids in the management of acute multiple sclerosis exacerbations. Acta Neurol Belg 2017; 117(3): 623-33.
  11. Ce P, Gedizlioglu M, Gelal F, Coban P, Ozbek G. Avascular necrosis of the bones: an overlooked complication of pulse steroid treatment of multiple sclerosis. Eur J Neurol 2006; 13(8): 857-61.
  12. Drescher W, Pufe T, Smeets R, Eisenhart-Rothe RV, Jager M, Tingart M. [Avascular necrosis of the hip - diagnosis and treatment]. Z Orthop Unfall 2011; 149(2): 231-40.
  13. Carulli C, Nistri L, Bracco L, Giannini M, Amato MP. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis. Clin Cases Miner Bone Metab 2015; 12(3): 257-9.
  14. Felson DT, Anderson JJ. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. Lancet 1987; 1(8538): 902-6.
  15. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 2002; 32(2): 94-124.
  16. Szilasiova J, Gdovinova Z, Jautova J, Baloghova J, Ficova M, Bohus P. Cutaneous vasculitis associated with interferon beta-1b treatment for multiple sclerosis. Clin Neuropharmacol 2009; 32(5): 301-3.
  17. Elgart GW, Sheremata W, Ahn YS. Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum. J Am Acad Dermatol 1997; 37(4): 553-8.
  18. Yildirim C, Nieuwenhuis S, Teunissen PF, Horrevoets AJ, van RN, van der Pouw Kraan TC. Interferon-Beta, a Decisive Factor in Angiogenesis and Arteriogenesis. J Interferon Cytokine Res 2015; 35(6): 411-20.