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Macrophage activation syndrome in adult dermatomyositis: a case-based review

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Abstract

Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases, characterized by fever, hepatosplenomegaly, and pancytopenia. Dermatomyositis (DM) is one of the causes of MAS; however, its clinical characteristics in DM patients remain unclear. This study aimed to present a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM complicated by MAS in a 29-year-old woman and to review the literatures including similar cases. Even though symptoms and cytopenia of our patient were refractory to combination therapy, including glucocorticoids, immunosuppressants, and plasma exchange, the administration of rituximab (RTX) resulted in rapid clinical improvement and glucocorticoid reduction. The literature review revealed 18 adult patients with DM associated MAS. Most patients developed MAS within 3 months from DM onset. A monotherapy of glucocorticoid was insufficient to control the disease, and the mortality of MAS in DM was higher than that of MAS in other rheumatic diseases, despite being treated by various means. RTX may be an effective treatment for patients with DM complicated by MAS who are refractory to conventional therapy. Anti-MDA5 antibody could influence the development of MAS; however, further investigations are needed to elucidate the association between myositis-specific antibody and MAS.

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References

  1. Janka GE, Lehmberg K (2014) Hemophagocytic syndromes—an update. Blood Rev 28:135–142. https://doi.org/10.1016/j.blre.2014.03.002

    Article  PubMed  Google Scholar 

  2. Atteritano M, David A, Bagnato G, Beninati C, Frisina A, Iaria C, Bagnato G, Cascio A (2012) Haemophagocytic syndrome in rheumatic patients. A systematic review. Eur Rev Med Pharmacol Sci 16:1414–1424

    CAS  PubMed  Google Scholar 

  3. Crayne CB, Albeituni S, Nichols KE, Cron RQ (2019) The immunology of macrophage activation syndrome. Front Immunol 10:119. https://doi.org/10.3389/fimmu.2019.00119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bae CB, Jung JY, Kim HA, Suh CH (2015) Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predictive factors, and prognosis in 21 patients. Medicine 94:e451. https://doi.org/10.1097/MD.0000000000000451

    Article  PubMed  PubMed Central  Google Scholar 

  5. Deane S, Selmi C, Teuber SS, Gershwin ME (2010) Macrophage activation syndrome in autoimmune disease. Int Arch Allergy Immunol 153:109–120. https://doi.org/10.1159/000312628

    Article  CAS  PubMed  Google Scholar 

  6. Cobos GA, Femia A, Vleugels RA (2020) Dermatomyositis: an update on diagnosis and treatment. Am J Clin Dermatol. https://doi.org/10.1007/s40257-020-00502-6

    Article  PubMed  Google Scholar 

  7. Betteridge Z, McHugh N (2016) Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med 280:8–23. https://doi.org/10.1111/joim.12451

    Article  CAS  PubMed  Google Scholar 

  8. Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, Khamashta MA, Bosch X (2014) Adult haemophagocytic syndrome. Lancet 383:1503–1516. https://doi.org/10.1016/S0140-6736(13)61048-X

    Article  PubMed  Google Scholar 

  9. Poddighe D, Dauyey K (2019) Macrophage activation syndrome in juvenile dermatomyositis: a systematic review. Rheumatol Int 40:695–702. https://doi.org/10.1007/s00296-019-04442-1

    Article  PubMed  Google Scholar 

  10. Kumakura S, Murakawa Y (2014) Clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome in adults. Arthritis Rheumatol 66:2297–2307. https://doi.org/10.1002/art.38672

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yasuda S, Tsutsumi A, Nakabayashi T, Horita T, Ichikawa K, Ieko M, Koike T (1998) Haemophagocytic syndrome in a patient with dermatomyositis. Br J Rheumatol 37:1357–1358. https://doi.org/10.1093/rheumatology/37.12.1357

    Article  CAS  PubMed  Google Scholar 

  12. Madaule S, Porte L, Couret B, Arlet-Suau E (2000) Fatal haemophagocytic syndrome in the course of dermatomyositis with anti-Mi2 antibodies. Rheumatology 39:1157–1158. https://doi.org/10.1093/rheumatology/39.10.1157

    Article  CAS  PubMed  Google Scholar 

  13. Yajima N, Wakabayashi K, Odai T, Isozaki T, Matsunawa M, Miwa Y, Negishi M, Ide H, Kasama T (2008) Clinical features of hemophagocytic syndrome in patients with dermatomyositis. J Rheumatol 35:1838–1841

    PubMed  Google Scholar 

  14. Thomas A, Appiah J, Langsam J, Parker S, Christian C (2013) Hemophagocytic lymphohistiocytosis associated with dermatomyositis: a case report. Conn Med 77:481–485

    PubMed  Google Scholar 

  15. Mizoguchi F, Takada K, Ishikawa K, Mizusawa H, Kohsaka H, Miyasaka N (2015) A case of dermatomyositis with rhabdomyolysis, rescued by intravenous immunoglobulin. Mod Rheumatol 25:646–648. https://doi.org/10.3109/14397595.2013.843753

    Article  PubMed  Google Scholar 

  16. Kaieda S, Yoshida N, Yamashita F, Okamoto M, Ida H, Hoshino T, Fukuda T (2015) Successful treatment of macrophage activation syndrome in a patient with dermatomyositis by combination with immunosuppressive therapy and plasmapheresis. Mod Rheumatol 25:962–966. https://doi.org/10.3109/14397595.2013.844402

    Article  CAS  PubMed  Google Scholar 

  17. Kerl K, Wolf IH, Cerroni L, Wolf P, French LE, Kerl H (2015) Hemophagocytosis in cutaneous autoimmune disease. Am J Dermatopathol 37:539–543. https://doi.org/10.1097/DAD.0000000000000166

    Article  PubMed  Google Scholar 

  18. Bazan-Socha S, Zolcinski M, Szostek M, Jurczyszyn A, Rucinska M, Demczuk S, Musial J (2017) A fatal case of acquired hemophagocytic lymphohistiocytosis (macrophage activation syndrome) in the initial course of dermatomyositis with anti-Jo-1 antibody. Int J Rheum Dis 20:2171–2174. https://doi.org/10.1111/1756-185X.12162

    Article  PubMed  Google Scholar 

  19. Komiya Y, Saito T, Mizoguchi F, Kohsaka H (2017) Hemophagocytic syndrome complicated with dermatomyositis controlled successfully with infliximab and conventional therapies. Intern Med 56:3237–3241. https://doi.org/10.2169/internalmedicine.7966-16

    Article  PubMed  PubMed Central  Google Scholar 

  20. Maramattom BV, Varghese R, Thomas J, Kachhare N (2017) Clinically amyopathic dermatomyositis associated with cerebral venous sinus thrombosis and macrophage activation syndrome. Neurol India 65:1412–1414. https://doi.org/10.4103/0028-3886.217937

    Article  PubMed  Google Scholar 

  21. Fujita Y, Fukui S, Suzuki T, Ishida M, Endo Y, Tsuji S et al (2018) Anti-MDA5 antibody-positive dermatomyositis complicated by autoimmune-associated hemophagocytic syndrome that was successfully treated with immunosuppressive therapy and plasmapheresis. Intern Med 57:3473–3478. https://doi.org/10.2169/internalmedicine.1121-18

    Article  PubMed  PubMed Central  Google Scholar 

  22. Liao HT, Yang CF, Tsai CY (2019) Hemophagocytic lymphohistiocytosis in dermatomyositis. Balkan Med J 36:62–63. https://doi.org/10.4274/balkanmedj.2018.1339

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yoshimatsu Y, Kotani T, Fujiki Y, Oda K, Kataoka T, Yamairi K, Hata K, Otani K, Kamimori T, Fujiwara H (2019) Successful treatment with intravenous high-dose immunoglobulin for cardiomyopathy in dermatomyositis complicated with rapid progressive interstitial pneumonia. Int J Rheum Dis 22:321–324. https://doi.org/10.1111/1756-185X.12746

    Article  CAS  PubMed  Google Scholar 

  24. Honda M, Moriyama M, Kondo M, Kumakura S, Sumita Y, Murakawa Y (2019) Three cases of autoimmune-associated haemophagocytic syndrome in dermatomyositis with anti-MDA5 autoantibody. Scand J Rheumatol. https://doi.org/10.1080/03009742.2019.1653493

    Article  PubMed  Google Scholar 

  25. Gavand PE, Serio I, Arnaud L, Costedoat-Chalumeau N, Carvelli J, Dossier A et al (2017) Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: a study of 103 episodes in 89 adult patients. Autoimmun Rev 16:743–749. https://doi.org/10.1016/j.autrev.2017.05.010

    Article  CAS  PubMed  Google Scholar 

  26. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131. https://doi.org/10.1002/pbc.21039

    Article  PubMed  Google Scholar 

  27. So MW, Koo BS, Kim YJ, Kim YG, Lee CK, Yoo B (2014) Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. Mod Rheumatol 24:855–857. https://doi.org/10.3109/14397595.2013.874740

    Article  CAS  PubMed  Google Scholar 

  28. Bakshi J, Hassan S, D'Cruz D, Chan A (2013) Rituximab therapy in refractory macrophage activation syndrome secondary to systemic lupus erythematosus. Lupus 22:1544–1546. https://doi.org/10.1177/0961203313504634

    Article  CAS  PubMed  Google Scholar 

  29. Junga Z, Stitt R, Tracy C, Keith M (2017) Novel use of rituximab in macrophage activation syndrome secondary to systemic lupus erythematosus. BMJ Case Rep. https://doi.org/10.1136/bcr-2017-221347

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kobayashi M, Takahashi Y, Yamashita H, Kaneko H, Mimori A (2011) Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome. Mod Rheumatol 21:92–96. https://doi.org/10.3109/s10165-010-0348-9

    Article  PubMed  Google Scholar 

  31. de Boysson H, Février J, Nicolle A, Auzary C, Geffray L (2013) Tocilizumab in the treatment of the adult-onset Still's disease: current clinical evidence. Clin Rheumatol 32:141–147. https://doi.org/10.1007/s10067-012-2105-2

    Article  PubMed  Google Scholar 

  32. Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC et al (2013) Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 65:314–324. https://doi.org/10.1002/art.37754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Aggarwal R, Loganathan P, Koontz D, Qi Z, Reed AM, Oddis CV (2017) Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. Rheumatology (Oxford) 56:247–254. https://doi.org/10.1093/rheumatology/kew396

    Article  CAS  Google Scholar 

  34. Ogawa Y, Kishida D, Shimojima Y, Hayashi K, Sekijima Y (2017) Effective administration of rituximab in anti-MDA5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease and refractory cutaneous involvement: a case report and literature review. Case Rep Rheumatol 2017:5386797. https://doi.org/10.1155/2017/5386797

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA (2017) Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology 56:26–36. https://doi.org/10.1093/rheumatology/kew146

    Article  CAS  PubMed  Google Scholar 

  36. Engel P, Gomez-Puerta JA, Ramos-Casals M, Lozano F, Bosch X (2011) Therapeutic targeting of B cells for rheumatic autoimmune diseases. Pharmacol Rev 63:127–156. https://doi.org/10.1124/pr.109.002006

    Article  CAS  PubMed  Google Scholar 

  37. Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T, Kuwana M (2009) RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum 60:2193–2200. https://doi.org/10.1002/art.24621

    Article  CAS  PubMed  Google Scholar 

  38. Gono T, Kawaguchi Y, Satoh T, Kuwana M, Katsumata Y, Takagi K, Masuda I, Tochimoto A, Baba S, Okamoto Y, Ota Y, Yamanaka H (2010) Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology 49:1713–1719. https://doi.org/10.1093/rheumatology/keq149

    Article  CAS  PubMed  Google Scholar 

  39. Li J, Liu Y, Li Y, Li F, Wang K, Pan W, Meng D (2018) Associations between anti-melanoma differentiation-associated gene 5 antibody and demographics, clinical characteristics and laboratory results of patients with dermatomyositis: a systematic meta-analysis. J Dermatol 45:46–52. https://doi.org/10.1111/1346-8138.14092

    Article  CAS  PubMed  Google Scholar 

  40. Nagashima T, Kamata Y, Iwamoto M, Okazaki H, Fukushima N, Minota S (2019) Liver dysfunction in anti-melanoma differentiation-associated gene 5 antibody-positive patients with dermatomyositis. Rheumatol Int 39:901–909. https://doi.org/10.1007/s00296-019-04255-2

    Article  CAS  PubMed  Google Scholar 

  41. Kawasumi H, Katsumata Y, Nishino A, Hirahara S, Kawaguchi Y, Kuwana M, Yamanaka H (2018) Association of serum soluble CD163 with polymyositis and dermatomyositis, especially in anti-MDA5 antibody-positive cases. J Rheumatol 45:947–955. https://doi.org/10.3899/jrheum.170997

    Article  CAS  PubMed  Google Scholar 

  42. Coca A, Bundy KW, Marston B, Huggins J, Looney RJ (2009) Macrophage activation syndrome: serological markers and treatment with anti-thymocyte globulin. Clin Immunol 132:10–18. https://doi.org/10.1016/j.clim.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  43. Peng QL, Zhang YL, Shu XM, Yang HB, Zhang L, Chen F, Lu X, Wang GC (2015) Elevated serum levels of soluble CD163 in polymyositis and dermatomyositis: associated with macrophage infiltration in muscle tissue. J Rheumatol 42:979–987. https://doi.org/10.3899/jrheum.141307

    Article  CAS  PubMed  Google Scholar 

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Funding

No funding was received for this study.

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Authors and Affiliations

  1. Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Dai Kishida, Noriko Sakaguchi, Ken-ichi Ueno, Satoru Ushiyama, Takanori Ichikawa, Tsuneaki Yoshinaga, Yasuhiro Shimojima & Yoshiki Sekijima

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  1. Dai Kishida
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  2. Noriko Sakaguchi
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  3. Ken-ichi Ueno
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  4. Satoru Ushiyama
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  5. Takanori Ichikawa
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  6. Tsuneaki Yoshinaga
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  7. Yasuhiro Shimojima
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Contributions

The study conception and design, data collection, review of literature, clinical management of patient, and drafting of the manuscript were performed by DK. Clinical management of patient, data collection, and critical review of the manuscript were performed by NS, SU, and TI. Review of literature, data collection, and editing of the manuscript were performed by KU. Study conception and design, clinical management of patient, and editing of the manuscript were performed by YS. Data collection and final approval were performed by YS. All authors read and approved the final manuscript.

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Correspondence to Dai Kishida.

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Dai Kishida, Noriko Sakaguchi, Ken-ichi Ueno, Satoru Ushiyama, Takanori Ichikawa, Tsuneaki Yoshinaga, Yasuhiro Shimojima, and Yoshiki Sekijima declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kishida, D., Sakaguchi, N., Ueno, Ki. et al. Macrophage activation syndrome in adult dermatomyositis: a case-based review. Rheumatol Int 40, 1151–1162 (2020). https://doi.org/10.1007/s00296-020-04590-9

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