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Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis

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Abstract

Anti-melanoma differentiation-associated gene 5–positive dermatomyositis (MDA5+ DM) is a rare autoimmune disease predominantly reported in East Asia. MDA5+ DM is an intractable disease with impressively high mortality due to rapid-progressive interstitial lung disease (RPILD). Other typical clinical manifestations comprise DM-specific rash (Gottron’s papules, heliotrope rash) and amyopathic/hypomyopathic muscle involvement. Multiple prognostic factors have been identified. Baseline forced vital capacity (FVC) %-based staging could serve as a simplified risk stratification system. Serum biomarkers including MDA5 Ab titers, ferritin, KL-6 levels, and CD4+CXCR4+ T cell percentage could provide additional surrogate value of ILD severity and treatment response, as well as potential predictive value for survival. Spontaneous pneumomediastinum (PNM), ground-glass opacity (GGO), and consolidation were demonstrated to be the most significant features in pulmonary high-resolution computed tomography (HRCT) findings of MDA5+ DM-ILD. The semi-quantitative assessment of lesions in HRCT has also been demonstrated relevant to the outcome. The current treatment of this disease is still largely empirical. Immunosuppressive treatments, i.e., “triple therapy” (combination of high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide) and JAK inhibitor-based therapy, are the mainstream regimens for MDA5+ DM-ILD, supported by the recently published trials. However, more efficacious regimen with favorable safety profile and high-level evidence is still urgently demanded for patients with MDA5+ DM-ILD, especially those at advanced-stage. We will summarize the terminology, etiology and pathogenesis, clinical features and outcome, prognostic factors, and treatment of MDA5+ DM-ILD in this review.

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References

  1. Sato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, Nishikawa T, Oddis CV, Ikeda Y (2005) Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 52(5):1571–1576. https://doi.org/10.1002/art.21023

    Article  CAS  PubMed  Google Scholar 

  2. 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(7):2193–2200. https://doi.org/10.1002/art.24621

    Article  CAS  PubMed  Google Scholar 

  3. Sontheimer RD (2002) Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis sine myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness? J Am Acad Dermatol 46(4):626–636. https://doi.org/10.1067/mjd.2002.120621

    Article  PubMed  Google Scholar 

  4. Mammen AL, Allenbach Y, Stenzel W, Benveniste O, Group EtWS (2020) 239th ENMC International Workshop: Classification of dermatomyositis, Amsterdam, the Netherlands, 14–16 December 2018. Neuromuscul Disord 30(1):70–92. https://doi.org/10.1016/j.nmd.2019.10.005

    Article  Google Scholar 

  5. Lian X, Zou J, Guo Q, Chen S, Lu L, Wang R, Zhou M, Fu Q, Ye Y, Bao C (2020) Mortality risk prediction in amyopathic dermatomyositis associated with interstitial lung disease: the FLAIR model. Chest. https://doi.org/10.1016/j.chest.2020.04.057

    Article  PubMed  Google Scholar 

  6. Lundberg IE, Tjarnlund A, Bottai M, Werth VP, Pilkington C, Visser M, Alfredsson L, Amato AA, Barohn RJ, Liang MH, Singh JA, Aggarwal R, Arnardottir S, Chinoy H, Cooper RG, Danko K, Dimachkie MM, Feldman BM, Torre IG, Gordon P, Hayashi T, Katz JD, Kohsaka H, Lachenbruch PA, Lang BA, Li Y, Oddis CV, Olesinska M, Reed AM, Rutkowska-Sak L, Sanner H, Selva-O’Callaghan A, Song YW, Vencovsky J, Ytterberg SR, Miller FW, Rider LG, International Myositis Classification Criteria Project consortium TEr, The Juvenile Dermatomyositis Cohort Biomarker S, Repository (2017) 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 76(12):1955–1964. https://doi.org/10.1136/annrheumdis-2017-211468

    Article  PubMed  Google Scholar 

  7. Cavazzana I, Fredi M, Ceribelli A, Mordenti C, Ferrari F, Carabellese N, Tincani A, Satoh M, Franceschini F (2016) Testing for myositis specific autoantibodies: comparison between line blot and immunoprecipitation assays in 57 myositis sera. J Immunol Methods 433:1–5. https://doi.org/10.1016/j.jim.2016.02.017

    Article  CAS  PubMed  Google Scholar 

  8. Sato S, Murakami A, Kuwajima A, Takehara K, Mimori T, Kawakami A, Mishima M, Suda T, Seishima M, Fujimoto M, Kuwana M (2016) Clinical utility of an enzyme-linked immunosorbent assay for detecting anti-melanoma differentiation-associated gene 5 autoantibodies. PLoS ONE 11(4):e0154285. https://doi.org/10.1371/journal.pone.0154285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Betteridge Z, Tansley S, Shaddick G, Chinoy H, Cooper RG, New RP, Lilleker JB, Vencovsky J, Chazarain L, Danko K, Nagy-Vincze M, Bodoki L, Dastmalchi M, Ekholm L, Lundberg IE, McHugh N, contributors UK, (2019) Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. J Autoimmun 101:48–55. https://doi.org/10.1016/j.jaut.2019.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hall JC, Casciola-Rosen L, Samedy L-A, Werner J, Owoyemi K, Danoff SK, Christopher-Stine L (2013) Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care & Research 65(8):1307–1315. https://doi.org/10.1002/acr.21992

    Article  CAS  Google Scholar 

  11. Moghadam-Kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R (2016) Anti-melanoma differentiation-associated gene 5 is associated with rapidly progressive lung disease and poor survival in US patients with amyopathic and myopathic dermatomyositis. Arthritis Care & Research 68(5):689–694. https://doi.org/10.1002/acr.22728

    Article  CAS  Google Scholar 

  12. Motegi S-i, Sekiguchi A, Toki S, Kishi C, Endo Y, Yasuda M, Ikeuchi H, Sakairi T, Hara K, Yamaguchi K, Maeno T, Hiromura K, Ishikawa O (2019) Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease. European Journal of Dermatology 29(5):511–517. https://doi.org/10.1684/ejd.2019.3634

    Article  CAS  PubMed  Google Scholar 

  13. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ, Fibrosis AEJACoIP, (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824. https://doi.org/10.1164/rccm.2009-040GL

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yamaguchi K, Yamaguchi A, Kashiwagi C, Sawada Y, Taguchi K, Umetsu K, Oshima K, Uchida M, Suzuki M, Kono S, Takemura M, Masubuchi H, Kitahara S, Hara K, Maeno T, Motegi S-i, Muro Y, Sakairi T, Hisada T, Kurabayashi M (2018) Differential clinical features of patients with clinically amyopathic dermatomyositis who have circulating anti-MDA5 autoantibodies with or without myositis-associated autoantibodies. Respir Med 140:1–5. https://doi.org/10.1016/j.rmed.2018.05.010

    Article  PubMed  Google Scholar 

  15. Jiang L, Wang Y, Peng Q, Shu X, Wang G, Wu X (2019) Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody. Clin Rheumatol 38(6):1655–1663. https://doi.org/10.1007/s10067-019-04457-w

    Article  PubMed  Google Scholar 

  16. Huang K, Vinik O, Shojania K, Yeung J, Shupak R, Nimmo M, Avina-Zubieta JA (2019) Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review. Rheumatol Int 39(11):1971–1981. https://doi.org/10.1007/s00296-019-04398-2

    Article  CAS  PubMed  Google Scholar 

  17. Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri S-y, Iwamoto N, Suzuki T, Nakashima Y, Tamai M, Arima K, Yamasaki S, Nakamura H, Origuchi T, Hamaguchi Y, Fujimoto M, Ishimatsu Y, Mukae H, Kuwana M, Kohno S, Eguchi K, Aoyagi K, Kawakami A (2012) The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology 51(7):1278–1284. https://doi.org/10.1093/rheumatology/ker518

    Article  CAS  PubMed  Google Scholar 

  18. Dias Junior AG, Sampaio NG, Rehwinkel J (2019) A balancing act: MDA5 in antiviral immunity and autoinflammation. Trends Microbiol 27(1):75–85. https://doi.org/10.1016/j.tim.2018.08.007

    Article  CAS  PubMed  Google Scholar 

  19. Muro Y, Sugiura K, Hoshino K, Akiyama M, Tamakoshi K (2011) Epidemiologic study of clinically amyopathic dermatomyositis and anti-melanoma differentiation-associated gene 5 antibodies in central Japan. Arthritis Research & Therapy 13 (6). https://doi.org/10.1186/ar3547

  20. Nishina N, Sato S, Masui K, Gono T, Kuwana M (2020) Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease. RMD Open 6 (2). https://doi.org/10.1136/rmdopen-2020-001202

  21. Gono T, Kawaguchi Y, Kuwana M, Sugiura T, Furuya T, Takagi K, Ichida H, Katsumata Y, Hanaoka M, Okamoto Y, Ota Y, Kataoka S, Yamanaka H (2012) HLA-DRB1*0101/*0405 is associated with susceptibility to anti-MDA5 antibody-positive dermatomyositis in the Japanese population. Arthritis Rheum 64(10):S822–S822

    Google Scholar 

  22. Rothwell S, Chinoy H, Lamb JA, Miller FW, Rider LG, Wedderburn LR, McHugh NJ, Mammen AL, Betteridge ZE, Tansley SL, Bowes J, Vencovsky J, Deakin CT, Danko K, Vidya L, Selva-O’Callaghan A, Pachman LM, Reed AM, Molberg O, Benveniste O, Mathiesen PR, Radstake T, Doria A, de Bleecker J, Lee AT, Hanna MG, Machado PM, Ollier WE, Gregersen PK, Padyukov L, O’Hanlon TP, Cooper RG, Lundberg IE, Myositis Genetics C (2019) Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups. Ann Rheum Dis 78(7):996–1002. https://doi.org/10.1136/annrheumdis-2019-215046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kochi Y, Kamatani Y, Kondo Y, Suzuki A, Kawakami E, Hiwa R, Momozawa Y, Fujimoto M, Jinnin M, Tanaka Y, Kanda T, Cooper RG, Chinoy H, Rothwell S, Lamb JA, Vencovsky J, Mann H, Ohmura K, Myouzen K, Ishigaki K, Nakashima R, Hosono Y, Tsuboi H, Kawasumi H, Iwasaki Y, Kajiyama H, Horita T, Ogawa-Momohara M, Takamura A, Tsunoda S, Shimizu J, Fujio K, Amano H, Mimori A, Kawakami A, Umehara H, Takeuchi T, Sano H, Muro Y, Atsumi T, Mimura T, Kawaguchi Y, Mimori T, Takahashi A, Kubo M, Kohsaka H, Sumida T, Yamamoto K (2018) Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis. Ann Rheum Dis 77(4):602–611. https://doi.org/10.1136/annrheumdis-2017-212149

    Article  CAS  PubMed  Google Scholar 

  24. Cassius C, Amode R, Delord M, Battistella M, Poirot J, How-Kit A, Lepelletier C, Jachiet M, de Masson A, Frumholtz L, Cordoliani F, Boccara D, Lehmann-Che J, Wong J, Dubanchet S, Alberdi AJ, Merandet M, Bagot M, Bensussan A, Bouazia J-D, Le Buanec H (2020) MDA5(+) D dermatomyositis is associated with stronger skin type I interferon transcriptomic signature with upregulation of IFN-kappa transcript. Journal of Investigative Dermatology 140(6):1276–1279. https://doi.org/10.1016/j.jid.2019.10.020

    Article  CAS  Google Scholar 

  25. Ono N, Kai K, Maruyama A, Sakai M, Sadanaga Y, Koarada S, Inoue T, Tada Y (2019) The relationship between type 1 IFN and vasculopathy in anti-MDA5 antibody-positive dermatomyositis patients. Rheumatology (Oxford) 58(5):786–791. https://doi.org/10.1093/rheumatology/key386

    Article  CAS  Google Scholar 

  26. Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, Pak K, Miller FW, Milisenda JC, Grau-Junyent JM, Selva-O’Callaghan A, Carrion-Ribas C, Paik JJ, Albayda J, Christopher-Stine L, Lloyd TE, Corse AM, Mammen AL (2020) Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis. Ann Rheum Dis 79(9):1234–1242. https://doi.org/10.1136/annrheumdis-2019-216599

    Article  CAS  PubMed  Google Scholar 

  27. Allenbach Y, Leroux G, Suarez-Calvet X, Preusse C, Gallardo E, Hervier B, Rigolet A, Hie M, Pehl D, Limal N, Hufnagl P, Zerbe N, Meyer A, Aouizerate J, Uzunhan Y, Maisonobe T, Goebel HH, Benveniste O, Stenzel W, French Myositis N (2016) Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies: common interferon signature but distinct NOS2 expression. Am J Pathol 186(3):691–700. https://doi.org/10.1016/j.ajpath.2015.11.010

    Article  CAS  PubMed  Google Scholar 

  28. Horai Y, Koga T, Fujikawa K, Takatani A, Nishino A, Nakashima Y, Suzuki T, Kawashiri S-y, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Ida H, Kakugawa T, Sakamoto N, Ishimatsu Y, Mukae H, Hamaguchi Y, Fujimoto M, Kuwana M, Origuchi T, Kohno S, Kawakami A (2015) Serum interferon-alpha is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis. Mod Rheumatol 25(1):85–89. https://doi.org/10.3109/14397595.2014.900843

    Article  CAS  PubMed  Google Scholar 

  29. Zhang SH, Zhao Y, Xie QB, Jiang Y, Wu YK, Yan B (2019) Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis. Br J Dermatol 180(5):1090–1098. https://doi.org/10.1111/bjd.16917

    Article  CAS  PubMed  Google Scholar 

  30. Gono T, Kaneko H, Kawaguchi Y, Hanaoka M, Kataoka S, Kuwana M, Takagi K, Ichida H, Katsumata Y, Ota Y, Kawasumi H, Yamanaka H (2014) Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford) 53(12):2196–2203. https://doi.org/10.1093/rheumatology/keu258

    Article  CAS  Google Scholar 

  31. Takada T, Ohashi K, Hayashi M, Asakawa K, Sakagami T, Kikuchi T, Sato S (2018) Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody. Respir Med 141:7–13. https://doi.org/10.1016/j.rmed.2018.06.012

    Article  PubMed  Google Scholar 

  32. Ishikawa Y, Iwata S, Hanami K, Nawata A, Zhang M, Yamagata K, Hirata S, Sakata K, Todoroki Y, Nakano K, Nakayamada S, Satoh M, Tanaka Y (2018) Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis. Arthritis Res Ther 20(1):240. https://doi.org/10.1186/s13075-018-1737-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen M, Quan C, Diao L, Xue F, Xue K, Wang B, Li X, Zhu X, Zheng J, Cao H (2018) Measurement of cytokines and chemokines and association with clinical severity of dermatomyositis and clinically amyopathic dermatomyositis. Br J Dermatol 179(6):1334–1341. https://doi.org/10.1111/bjd.17079

    Article  CAS  PubMed  Google Scholar 

  34. Abe Y, Matsushita M, Tada K, Yamaji K, Takasaki Y, Tamura N (2017) Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody-positive inflammatory myositis. Rheumatology (Oxford) 56(9):1492–1497. https://doi.org/10.1093/rheumatology/kex188

    Article  CAS  Google Scholar 

  35. Chen Z, Cao M, Nieves Plana M, Liang J, Cai H, Kuwana M, Sun L (2013) Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: a review of the literature and a meta-analysis. Arthritis Care & Research 65(8):1316–1324. https://doi.org/10.1002/acr.21985

    Article  CAS  Google Scholar 

  36. Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, Takagi K, Baba S, Okamoto Y, Ota Y, Yamanaka H (2012) Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology 51(9):1563–1570. https://doi.org/10.1093/rheumatology/kes102

    Article  CAS  PubMed  Google Scholar 

  37. So H, Ip RWK, Wong VTL, Yip RML (2018) Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and clinical correlations. International Journal of Rheumatic Diseases 21(5):1076–1081. https://doi.org/10.1111/1756-185x.13268

    Article  CAS  PubMed  Google Scholar 

  38. Ye S, Chen X-x, Lu X-y, Wu M-f, Deng Y, Huang W-q, Guo Q, Yang C-d, Gu Y-y, Bao C-d, Chen S-l (2007) Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease: a retrospective cohort study. Clin Rheumatol 26(10):1647–1654. https://doi.org/10.1007/s10067-007-0562-9

    Article  PubMed  Google Scholar 

  39. Tsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H, Hirata S, Nojima T, Sugiyama E, Hatta K, Taguchi Y, Katayama M, Tanizawa K, Handa T, Uozumi R, Akizuki S, Murakami K, Hashimoto M, Tanaka M, Ohmura K, Mimori T (2020) Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with high-dose glucocorticoid, tacrolimus, and cyclophosphamide in interstitial lung diseases accompanied by anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Arthritis Rheumatol 72(3):488–498. https://doi.org/10.1002/art.41105

    Article  CAS  PubMed  Google Scholar 

  40. Fujiki Y, Kotani T, Isoda K, Ishida T, Shoda T, Yoshida S, Takeuchi T, Makino S (2018) Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients. Mod Rheumatol 28(1):133–140. https://doi.org/10.1080/14397595.2017.1318468

    Article  CAS  PubMed  Google Scholar 

  41. Yamaguchi K, Yamaguchi A, Itai M, Kashiwagi C, Takehara K, Aoki S, Sawada Y, Taguchi K, Umetsu K, Oshima K, Uchida M, Takemura M, Hara K, Motegi S-I, Muro Y, Nakasatomi M, Sakairi T, Hiromura K, Kurabayashi M, Maeno T (2019) Clinical features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis complicated by spontaneous pneumomediastinum. Clin Rheumatol 38(12):3443–3450. https://doi.org/10.1007/s10067-019-04729-5

    Article  PubMed  Google Scholar 

  42. Zhou M, Ye Y, Yan N, Lian X, Bao C, Guo Q (2020) Noninvasive positive pressure ventilator deteriorates the outcome of pneumomediastinum in anti-MDA5 antibody-positive clinically amyopathic dermatomyositis. Clin Rheumatol 39(6):1919–1927. https://doi.org/10.1007/s10067-019-04918-2

    Article  PubMed  Google Scholar 

  43. Hozumi H, Fujisawa T, Nakashima R, Johkoh T, Sumikawa H, Murakami A, Enomoto N, Inui N, Nakamura Y, Hosono Y, Imura Y, Mimori T, Suda T (2016) Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease. Respir Med 121:91–99. https://doi.org/10.1016/j.rmed.2016.10.019

    Article  PubMed  Google Scholar 

  44. Zou J, Guo Q, Chi J, Wu H, Bao C (2015) HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients. Clin Rheumatol 34(4):707–714. https://doi.org/10.1007/s10067-015-2866-5

    Article  PubMed  Google Scholar 

  45. Zuo Y, Ye L, Liu M, Li S, Liu W, Chen F, Lu X, Gordon P, Wang G, Shu X (2020) Clinical significance of radiological patterns of HRCT and their association with macrophage activation in dermatomyositis. Rheumatology (Oxford) 59(10):2829–2837. https://doi.org/10.1093/rheumatology/keaa034

    Article  Google Scholar 

  46. Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Oga T, Chin K, Nagai S, Mimori T, Mishima M (2011) HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody. Respir Med 105(9):1380–1387. https://doi.org/10.1016/j.rmed.2011.05.006

    Article  PubMed  Google Scholar 

  47. Chino H, Sekine A, Baba T, Iwasawa T, Okudela K, Takemura T, Itoh H, Sato S, Suzuki Y, Ogura T (2016) Radiological and pathological correlation in anti-MDA5 antibody-positive interstitial lung disease: rapidly progressive perilobular opacities and diffuse alveolar damage. Intern Med 55(16):2241–2246. https://doi.org/10.2169/internalmedicine.55.5774

    Article  PubMed  Google Scholar 

  48. Chino H, Sekine A, Baba T, Kitamura H, Iwasawa T, Okudela K, Takemura T, Itoh H, Sato S, Suzuki Y, Ogura T (2019) Interstitial lung disease with anti-melanoma differentiation-associated protein 5 antibody: rapidly progressive perilobular opacity. Intern Med 58(18):2605–2613. https://doi.org/10.2169/internalmedicine.2328-18

    Article  PubMed  PubMed Central  Google Scholar 

  49. Nishioka A, Tsunoda S, Abe T, Yoshikawa T, Takata M, Kitano M, Matsui K, Nakashima R, Hosono Y, Ohmura K, Mimori T, Sano H (2019) Serum neopterin as well as ferritin, soluble interleukin-2 receptor, KL-6 and anti-MDA5 antibody titer provide markers of the response to therapy in patients with interstitial lung disease complicating anti-MDA5 antibody-positive dermatomyositis. Mod Rheumatol 29(5):814–820. https://doi.org/10.1080/14397595.2018.1548918

    Article  CAS  PubMed  Google Scholar 

  50. Matsushita T, Mizumaki K, Kano M, Yagi N, Tennichi M, Takeuchi A, Okamoto Y, Hamaguchi Y, Murakami A, Hasegawa M, Kuwana M, Fujimoto M, Takehara K (2017) Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis. Br J Dermatol 176(2):395–402. https://doi.org/10.1111/bjd.14882

    Article  CAS  PubMed  Google Scholar 

  51. Endo Y, Koga T, Ishida M, Fujita Y, Tsuji S, Takatani A, Shimizu T, Sumiyoshi R, Igawa T, Umeda M, Fukui S, Nishino A, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Kuwana M, Hosono Y, Mimori T, Kawakami A (2018) Recurrence of anti-MDA5 antibody-positive clinically amyopathic dermatomyositis after long-term remission: a case report. Medicine (Baltimore) 97(26):e11024. https://doi.org/10.1097/MD.0000000000011024

    Article  Google Scholar 

  52. 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 (Oxford) 49(9):1713–1719. https://doi.org/10.1093/rheumatology/keq149

    Article  CAS  Google Scholar 

  53. Xu Y, Yang CS, Li YJ, Liu XD, Wang JN, Zhao Q, Xiao WG, Yang PT (2016) Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis. Clin Rheumatol 35(1):113–116. https://doi.org/10.1007/s10067-015-3139-z

    Article  CAS  PubMed  Google Scholar 

  54. Kurasawa K, Arai S, Namiki Y, Tanaka A, Takamura Y, Owada T, Arima M, Maezawa R (2018) Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford) 57(12):2114–2119. https://doi.org/10.1093/rheumatology/key188

    Article  CAS  Google Scholar 

  55. Ito M, Kaise S, Suzuki S, Kazuta Y, Sato Y, Miyata M, Nishimaki T, Nakamura N, Kasukawa R (1999) Clinico-laboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease. Clin Rheumatol 18(6):462–467. https://doi.org/10.1007/s100670050139

    Article  CAS  PubMed  Google Scholar 

  56. Yoshifuji H (2015) Biomarkers and autoantibodies of interstitial lung disease with idiopathic inflammatory myopathies. Clin Med Insights Circ Respir Pulm Med 9(Suppl 1):141–146. https://doi.org/10.4137/CCRPM.S36748

    Article  PubMed  Google Scholar 

  57. Kohno N, Akiyama M, Kyoizumi S, Hakoda M, Kobuke K, Yamakido M (1988) Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Jpn J Clin Oncol 18(3):203–216

    CAS  PubMed  Google Scholar 

  58. Bandoh S, Fujita J, Ohtsuki Y, Ueda Y, Hojo S, Tokuda M, Dobashi H, Kurata N, Yoshinouchi T, Kohno N, Takahara J (2000) Sequential changes of KL-6 in sera of patients with interstitial pneumonia associated with polymyositis/dermatomyositis. Ann Rheum Dis 59(4):257–262. https://doi.org/10.1136/ard.59.4.257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ye Y, Fu Q, Wang R, Guo Q, Bao C (2019) Serum KL-6 level is a prognostic marker in patients with anti-MDA5 antibody-positive dermatomyositis associated with interstitial lung disease. J Clin Lab Anal 33(8):e22978. https://doi.org/10.1002/jcla.22978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wang K, Zhao J, Chen Z, Li T, Tan X, Zheng Y, Gu L, Guo L, Sun F, Wang H, Li J, Wang X, Riemekasten G, Ye S (2019) CD4+CXCR4+ T cells as a novel prognostic biomarker in patients with idiopathic inflammatory myopathy-associated interstitial lung disease. Rheumatology (Oxford) 58(3):511–521. https://doi.org/10.1093/rheumatology/key341

    Article  CAS  Google Scholar 

  61. Suzuki J, Morimoto S, Amano H, Tokano Y, Takasaki Y, Hashimoto H (2001) Serum levels of interleukin 15 in patients with rheumatic diseases. J Rheumatol 28(11):2389–2391

    CAS  PubMed  Google Scholar 

  62. Zong M, Loell I, Lindroos E, Nader GA, Alexanderson H, Hallengren CS, Borg K, Arnardottir S, McInnes IB, Lundberg IE (2012) Effects of immunosuppressive treatment on interleukin-15 and interleukin-15 receptor alpha expression in muscle tissue of patients with polymyositis or dermatomyositis. Ann Rheum Dis 71(6):1055–1063. https://doi.org/10.1136/annrheumdis-2011-200495

    Article  CAS  PubMed  Google Scholar 

  63. Shimizu T, Koga T, Furukawa K, Horai Y, Fujikawa K, Okada A, Okamoto M, Endo Y, Tsuji S, Takatani A, Umeda M, Fukui S, Sumiyoshi R, Kawashiri SY, Iwamoto N, Igawa T, Ichinose K, Tamai M, Sakamoto N, Nakamura H, Origuchi T, Mukae H, Kuwana M, Kawakami A (2020) IL-15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis. J Intern Med. https://doi.org/10.1111/joim.13154

    Article  PubMed  Google Scholar 

  64. Nara M, Komatsuda A, Omokawa A, Togashi M, Okuyama S, Sawada K, Wakui H (2014) Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. Mod Rheumatol 24(4):633–636. https://doi.org/10.3109/14397595.2013.844390

    Article  CAS  PubMed  Google Scholar 

  65. Romero-Bueno F, Diaz Del Campo P, Trallero-Araguas E, Ruiz-Rodriguez JC, Castellvi I, Rodriguez-Nieto MJ, Martinez-Becerra MJ, Sanchez-Pernaute O, Pinal-Fernandez I, Solanich X, Gono T, Gonzalez-Gay MA, Plana MN, Selva-O’Callaghan A, group M, (2020) Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease. Semin Arthritis Rheum 50(4):776–790. https://doi.org/10.1016/j.semarthrit.2020.03.007

    Article  CAS  PubMed  Google Scholar 

  66. Chen Z, Wang X, Ye S (2019) Tofacitinib in amyopathic dermatomyositis-associated interstitial lung disease. N Engl J Med 381(3):291–293. https://doi.org/10.1056/NEJMc1900045

    Article  PubMed  Google Scholar 

  67. So H, Wong VTL, Lao VWN, Pang HT, Yip RML (2018) Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis. Clin Rheumatol 37(7):1983–1989. https://doi.org/10.1007/s10067-018-4122-2

    Article  PubMed  Google Scholar 

  68. Zou J, Li T, Huang X, Chen S, Guo Q, Bao C (2014) Basiliximab may improve the survival rate of rapidly progressive interstitial pneumonia in patients with clinically amyopathic dermatomyositis with anti-MDA5 antibody. Ann Rheum Dis 73(8):1591–1593. https://doi.org/10.1136/annrheumdis-2014-205278

    Article  CAS  PubMed  Google Scholar 

  69. Koichi Y, Aya Y, Megumi U, Shunichi K, Masafumi S, Hiroaki M, Masahiko K, Shinsuke K, Manabu U, Kenichiro H, Fumiaki A, Nozomi A, Toshitaka M, Masayoshi Y, Chikako K, Yoshinao M, Tatsuo S, Masahiko K (2017) A case of anti-MDA5-positive rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis ameliorated by rituximab, in addition to standard immunosuppressive treatment. Mod Rheumatol 27(3):536–540. https://doi.org/10.3109/14397595.2015.1014140

    Article  PubMed  Google Scholar 

  70. Abe Y, Kusaoi M, Tada K, Yamaji K, Tamura N (2020) Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy. Rheumatology (Oxford) 59(4):767–771. https://doi.org/10.1093/rheumatology/kez357

    Article  CAS  Google Scholar 

  71. Kagawa H, Tsujino K, Yamamoto Y, Iwai A, Hara R, Matsuki T, Fukushima K, Oshitani Y, Yoshimura K, Miki M, Miki K, Kitada S, Mori M, Kida H (2020) Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease: a case report. Respir Med Case Rep 29:101016. https://doi.org/10.1016/j.rmcr.2020.101016

    Article  PubMed  PubMed Central  Google Scholar 

  72. Okabayashi H, Ichiyasu H, Hirooka S, Akaike K, Kojima K, Jodai T, Sakamoto Y, Ideguchi H, Hamada S, Yoshida C, Hirosako S, Okamoto S, Kohrogi H (2017) Clinical effects of direct hemoperfusion using a polymyxin B-immobilized fiber column in clinically amyopathic dermatomyositis-associated rapidly progressive interstitial pneumonias. BMC Pulm Med 17(1):134. https://doi.org/10.1186/s12890-017-0479-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Li T, Guo L, Chen Z, Gu L, Sun F, Tan X, Chen S, Wang X, Ye S (2016) Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis. Sci Rep 6:33226. https://doi.org/10.1038/srep33226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Leclair V, Labirua-Iturburu A, Lundberg IE (2018) Successful lung transplantation in a case of rapidly progressive interstitial lung disease associated with antimelanoma differentiation-associated gene 5 antibodies. J Rheumatol 45(4):581–583. https://doi.org/10.3899/jrheum.171047

    Article  PubMed  Google Scholar 

  75. Huang K, Levy RD, Avina-Zubieta JA (2020) Successful lung transplant in rapid progressive interstitial lung disease associated with anti-melanoma differentiation associated gene 5. Rheumatology (Oxford) 59(8):2161–2163. https://doi.org/10.1093/rheumatology/keaa032

    Article  Google Scholar 

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  1. Department of Rheumatology, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, 2000 Jiangyue Road, Shanghai, 201112, China

    Wanlong Wu, Li Guo, Yakai Fu, Kaiwen Wang, Danting Zhang, Wenwen Xu, Zhiwei Chen & Shuang Ye

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Wu, W., Guo, L., Fu, Y. et al. Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis. Clinic Rev Allerg Immunol 60, 293–304 (2021). https://doi.org/10.1007/s12016-020-08822-5

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