Skip to main content

Advertisement

SpringerLink
Log in

Disease characteristics and clinical outcomes of adults and children with anti-MDA-5 antibody-associated myositis: a prospective observational bicentric study

  • Observational Research
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

To study the demographic, clinical and serologic characteristics of anti-MDA5-positive DM from two geographically and ethnically disparate inception cohorts in India. To identify the clinical and serological parameters at inception that could predict mortality among these individuals. Individuals with anti-MDA5 antibody-positive DM diagnosed between 2017 and 2020 from two centres in India were prospectively followed up. The clinical and serological characteristics at baseline and the treatment outcome at follow-up were assessed for this study. Anti-MDA5 antibody was positive in 25 (7.5%) out of the 330 individuals with myositis. These 25 (21 adults, 4 juvenile) patients were followed up for a median duration of 14 months. Among adults, a majority had cutaneous manifestations 21 (84%) followed by, arthritis 17 (80%), and interstitial lung disease 12 (ILD, 57.1%). Four (19%) had rapidly progressive ILD (RP-ILD). Eight (38%) presented as clinically amyopathic DM. Among cutaneous manifestations, majority (62%) had classic features (gottron’s papules/sign, heliotrope rash) while 8 (38%) had cutaneous ulceration and 2 each had periorbital edema and tendon rupture. Eight (38%) were positive for anti-Ro-52 antibody. Out of 21 adults, 8 (38%) succumbed to the diseases. RP-ILD (n = 4; 19%), ulcerative gottron’s (n = 5) and anti-Ro-52 (n = 8) were significantly associated with mortality (p < 0.05). Upon binary logistic regression, positive anti-Ro-52 antibody predicted mortality [HR 17.3 (95%CI 1.4–210, p = 0.025)]. All juvenile anti-MDA5-positive DMs had classic cutaneous features with 2 of them having ulcerative gottron’s. None of the juvenile patients had ILD and everyone survived till the last follow-up. Indian adults with anti-MDA5 DM have high mortality. Rarer atypical features like tendon rupture or periorbital edema could assist in diagnosis. Ulcerative gottron’s, positive anti-Ro 52 antibodies, and RP-ILD are valuable clinical-serological markers that portend poor prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author, KC, upon reasonable request.

Abbreviations

ACR:

American College of Rheumatology

Anti-MDA5 DM:

Anti-MDA-5-associated dermatomyositis

EULAR:

European league against rheumatism

CPK:

Creatine phosphokinase

CSM:

Core set measures

CT:

Computed tomography

CYC:

Cyclophosphamide

DM:

Dermatomyositis

IFN:

Interferon

IIM:

Idiopathic inflammatory myositis

ILD:

Interstitial lung disease

IS:

Immunosuppression

IVIG:

Intravenous immunoglobulin

JDM:

Juvenile dermatomyositis

LDH:

Lactate dehydrogenase

MAA:

Myositis-associated antibodies

MMT8:

Manual muscle testing 8

MPS:

Methylprednisolone

MSA:

Myositis-specific antibodies

PM:

Polymyositis

RP-ILD:

Rapidly progressive ILD

References

  1. Chaisson NF, Paik J, Orbai A-M, Casciola-Rosen L, Fiorentino D, Danoff S et al (2012) A novel dermato-pulmonary syndrome associated with MDA-5 antibodies. Medicine 91(4):220–228

    Article  PubMed  Google Scholar 

  2. Kurtzman DJB, Vleugels RA (2018) Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: a concise review with an emphasis on distinctive clinical features. J Am Acad Dermatol 78(4):776–785

    Article  CAS  PubMed  Google Scholar 

  3. Hall JC, Casciola-Rosen L, Samedy L-A, Werner J, Owoyemi K, Danoff SK et al (2013) Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res 65(8):1307–1315

    Article  CAS  Google Scholar 

  4. Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T et al (2011) Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. Arch Dermatol 147(4):391–398

    Article  CAS  PubMed  Google Scholar 

  5. Chen Z, Hu W, Wang Y, Guo Z, Sun L, Kuwana M (2015) Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis. Clin Rheumatol 34(9):1627–1631

    Article  PubMed  Google Scholar 

  6. Betteridge Z, Tansley S, Shaddick G, Chinoy H, Cooper RG, New RP et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sato S, Masui K, Nishina N, Kawaguchi Y, Kawakami A, Tamura M et al (2018) Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients. Rheumatology 57(7):1212–1221

    Article  CAS  PubMed  Google Scholar 

  8. Xing J, Watkins WS, Hu Y, Huff CD, Sabo A, Muzny DM et al (2010) Genetic diversity in India and the inference of Eurasian population expansion. Genome Biol 11(11):R113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mariaselvam CM, Fortier C, Charron D, Krishnamoorthy R, Tamouza R, Negi VS (2016) HLA class II alleles influence rheumatoid arthritis susceptibility and autoantibody status in South Indian Tamil population. HLA 88(5):253–258

    Article  CAS  PubMed  Google Scholar 

  10. Srivastava R, Phatak S, Yadav A, Bajpai P, Aggarwal A (2016) HLA B27 typing in 511 children with juvenile idiopathic arthritis from India. Rheumatol Int 36(10):1407–1411

    Article  CAS  PubMed  Google Scholar 

  11. Kavadichanda CG, Seth G, Kumar G, Gulati R, Negi VS (2019) Clinical correlates of HLA-B*27 and its subtypes in enthesitis-related arthritis variant of juvenile idiopathic arthritis in south Indian Tamil patients. Int J Rheum Dis 22(7):1289–1296

    Article  CAS  PubMed  Google Scholar 

  12. 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 Res Ther 13(6):R214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Census of India: Reference Material (2020) https://censusindia.gov.in/Ad_Campaign/Referance_material.html. Accessed 7 Dec 2020

  14. Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M et al (2017) EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 76(12):1955–1964

    Article  PubMed  Google Scholar 

  15. Chengappa KG, Adarsh MB, Negi VS, Saikumar D (2019) PC0098: clinical and immunological profile of patients with idiopathic inflammatory myopathies in a tertiary care hospital. Indian J Rheumatol 14(Suppl S2):99–249

    Google Scholar 

  16. Mehta P, Gupta L (2020) Combined case record forms for collaborative datasets of patients and controls of idiopathic inflammatory myopathies. Indian J Rheumatol. https://doi.org/10.4103/injr.injr_56_20

    Article  Google Scholar 

  17. Gupta L, Appani SK, Janardana R, Muhammed H, Lawrence A, Amin S et al (2019) Meeting report: MyoIN—Pan-India collaborative network for myositis research. Indian J Rheumatol 14(2):136

    Article  Google Scholar 

  18. Naveen R, Anuja A, Rai M, Agarwal V, Gupta L (2020) Development of the myocite biobank: cost-efficient model of public sector investigator-driven biobank for idiopathic inflammatory myositis. Indian J Rheumatol 15(6):194

    Article  Google Scholar 

  19. Gupta L, Naveen R, Gaur P, Agarwal V, Aggarwal R (2021) Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis. Semin Arthritis Rheum 51(1):113–120

    Article  CAS  PubMed  Google Scholar 

  20. Rider LG, Aggarwal R, Machado PM, Hogrel J-Y, Reed AM, Christopher-Stine L et al (2018) Update on outcome assessment in myositis. Nat Rev Rheumatol 14(5):303–318

    Article  PubMed  PubMed Central  Google Scholar 

  21. Jablonski R, Bhorade S, Strek ME, Dematte J (2020) Recognition and management of myositis-associated rapidly progressive interstitial lung disease. Chest 158(1):252–263

    Article  PubMed  Google Scholar 

  22. 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(2):314–324

    Article  CAS  PubMed  Google Scholar 

  23. Feldman BM, Rider LG, Reed AM, Pachman LM (2008) Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet 371(9631):2201–2212

    Article  PubMed  Google Scholar 

  24. Machado PM, Mehta P, Gupta L (2021) Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry. Rheumatol Int. https://doi.org/10.1007/s00296-021-04819-1

    Article  PubMed  PubMed Central  Google Scholar 

  25. Rathore U, Haldule S, Gupta L (2020) Psoriasiform rashes as the first manifestation of anti-MDA5 associated myositis. Rheumatology. https://doi.org/10.1093/rheumatology/keaa821/6025468

    Article  Google Scholar 

  26. Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T et al (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

    Article  CAS  PubMed  Google Scholar 

  27. 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 Res 68(5):689–694

    Article  CAS  Google Scholar 

  28. Nakashima R, Hosono Y, Mimori T (2016) Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus 25(8):925–933

    Article  CAS  PubMed  Google Scholar 

  29. Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L (2011) The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study. J Am Acad Dermatol 65(1):25–34

    Article  PubMed  PubMed Central  Google Scholar 

  30. Narang NS, Casciola-Rosen L, Li S, Chung L, Fiorentino DF (2015) Cutaneous ulceration in dermatomyositis: association with anti-melanoma differentiation-associated gene 5 antibodies and interstitial lung disease: analysis of skin ulcers in dermatomyositis. Arthritis Care Res 67(5):667–672

    Article  CAS  Google Scholar 

  31. Tomb R, Stephan F (2002) Perforating skin ulcers occurring in an adult with dermatomyositis. Ann Dermatol Venereol 129(12):1383–1385

    CAS  PubMed  Google Scholar 

  32. Nakamura S, Nakagawa J (2004) Recurrent extensor tendon rupture in adult-onset dermatomyositis: a case report. Clin Rheumatol 24(4):409–410

    Article  PubMed  Google Scholar 

  33. Tu J, McLean-Tooke A, Junckerstorff R (2014) Increasing recognition of dermatomyositis with subcutaneous edema—is this a poorer prognostic marker? Dermatol Online J 20(1):21244

    PubMed  Google Scholar 

  34. Pappa E, Gkeka M, Protogerou A, Marinos L, Loupa C, Christopoulos C (2018) Case report: clinically amyopathic dermatomyositis presenting acutely with isolated facial edema. F1000Research 7:60

    PubMed  PubMed Central  Google Scholar 

  35. Milisenda JC, Doti PI, Prieto-González S, Grau JM (2014) Dermatomyositis presenting with severe subcutaneous edema: five additional cases and review of the literature. Semin Arthritis Rheum 44(2):228–233

    Article  PubMed  Google Scholar 

  36. Hall JC, Casciola-Rosen L, Samedy L-A, Werner J, Owoyemi K, Danoff SK et al (2013) Anti-MDA5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res 65(8):1307–1315

    Article  CAS  Google Scholar 

  37. Chen F, Zuo Y, Li S, Shi J, Wang G, Shu X (2019) Clinical characteristics of dermatomyositis patients with isolated anti-Ro-52 antibody associated rapid progressive interstitial lung disease: data from the largest single Chinese center. Respir Med 155:127–132

    Article  PubMed  Google Scholar 

  38. Hoshino K, Muro Y, Sugiura K, Tomita Y, Nakashima R, Mimori T (2010) Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis. Rheumatology 49(9):1726–1733

    Article  CAS  PubMed  Google Scholar 

  39. Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y et al (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

    Article  CAS  PubMed  Google Scholar 

  40. Gerami P, Walling HW, Lewis J, Doughty L, Sontheimer RD (2007) A systematic review of juvenile-onset clinically amyopathic dermatomyositis. Br J Dermatol 157(4):637–644

    Article  CAS  PubMed  Google Scholar 

  41. Tansley SL, Betteridge ZE, Gunawardena H, Jacques TS, Owens CM, Pilkington C et al (2014) Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study. Arthritis Res Ther 16(4):R138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chen Z, Wang Y, Kuwana M, Xu X, Hu W, Feng X et al (2017) HLA-DRB1 alleles as genetic risk factors for the development of anti-MDA5 antibodies in patients with dermatomyositis. J Rheumatol 44(9):1389–1393

    Article  CAS  PubMed  Google Scholar 

  43. Gono T, Kawaguchi Y, Kuwana M, Sugiura T, Furuya T, Takagi K et al (2012) Brief Report: Association of HLA–DRB1*0101/*0405 with susceptibility to anti–melanoma differentiation–associated gene 5 antibody–positive dermatomyositis in the Japanese population. Arthritis Rheum 64(11):3736–3740

    Article  CAS  PubMed  Google Scholar 

  44. Lin JM, Zhang YB, Peng QL, Yang HB, Shi JL, Gu ML et al (2017) Genetic association of HLA-DRB1 multiple polymorphisms with dermatomyositis in Chinese population. HLA 90(6):354–359

    Article  CAS  PubMed  Google Scholar 

  45. Vuillard C, de Pineton Chambrun M, de Prost N, Guérin C, Schmidt M, Dargent A et al (2018) Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study. Ann Intensive Care 8(1):87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Romero-Bueno F, Diaz Del Campo P, Trallero-Araguás E, Ruiz-Rodríguez JC, Castellvi I, Rodriguez-Nieto MJ et al (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

    Article  CAS  PubMed  Google Scholar 

  47. Hall JC, Rosen A (2010) Type I interferons: crucial participants in disease amplification in autoimmunity. Nat Rev Rheumatol 6(1):40–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ono N, Kai K, Maruyama A, Sakai M, Sadanaga Y, Koarada S et al (2020) The relationship between type 1 IFN and vasculopathy in anti-MDA5 antibody-positive dermatomyositis patients. Rheumatology 59(4):918

    Article  PubMed  Google Scholar 

  49. Rosen A, Casciola-Rosen L, Ahearn J (1995) Novel packages of viral and self-antigens are generated during apoptosis. J Exp Med 181(4):1557–1561

    Article  CAS  PubMed  Google Scholar 

  50. Hoa S, Troyanov Y, Fritzler MJ, Targoff IN, Chartrand S, Mansour AM et al (2018) Describing and expanding the clinical phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease: case series of nine Canadian patients and literature review. Scand J Rheumatol 47(3):210–224

    Article  CAS  PubMed  Google Scholar 

  51. Sakamoto S, Okamoto M, Kaieda S, Fujimoto K, Nagata S, Tominaga M et al (2018) Low positive titer of anti-melanoma differentiation-associated gene 5 antibody is not associated with a poor long-term outcome of interstitial lung disease in patients with dermatomyositis. Respir Investig 56(6):464–472

    Article  PubMed  Google Scholar 

  52. Matsushita T, Mizumaki K, Kano M, Yagi N, Tennichi M, Takeuchi A et al (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

    Article  CAS  PubMed  Google Scholar 

  53. Motegi S-I, Sekiguchi A, Toki S, Kishi C, Endo Y, Yasuda M et al (2019) Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease. Eur J Dermatol EJD 29(5):511–517

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

SK received intramural grant from Jawaharlal institute of postgraduate medical education and research institute (Proposal No: 119, on 19.08.2019) and from Indian Rheumatology Association grant for 2019 on 13.05.2020.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India

    Sai Kumar Dunga, Chengappa Kavadichanda & Vir Singh Negi

  2. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, 226014, Uttar Pradesh, India

    Latika Gupta, R. Naveen & Vikas Agarwal

Authors
  1. Sai Kumar Dunga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chengappa Kavadichanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Latika Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Naveen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vikas Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vir Singh Negi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KC and LG conceptualised the idea and drafted the methodology. VA and VN reviewed the study design. SK and NR collected data and analysed. SK drafted the manuscript with inputs from KC and LG. KC, LG, VA and VN were involved in reviewing and editing the manuscript. All the authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Chengappa Kavadichanda or Latika Gupta.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments after obtaining clearance independently from Jawaharlal institute of postgraduate medical education and research institute ethics committee(JIP/IEC/2019/250) and Sanjay Gandhi postgraduate Institute’s institute ethics committee (2017-41-IP-76).

Patient consent

A written informed consent was obtained from the study participants.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Disclaimer: Part of this manuscript has been published as Mehta P et al. as high early mortality in idiopathic inflammatory myopathies: results from the Inception Cohort at a Tertiary Care Centre in Northern India. Rheumatology 2021 and Rathore U et al. Psoriasiform rashes as the first manifestation of anti-MDA5 associated myositis. Rheumatology 2020 Dec 7.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dunga, S.K., Kavadichanda, C., Gupta, L. et al. Disease characteristics and clinical outcomes of adults and children with anti-MDA-5 antibody-associated myositis: a prospective observational bicentric study. Rheumatol Int 42, 1155–1165 (2022). https://doi.org/10.1007/s00296-021-04897-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-021-04897-1

Keywords

Search

Navigation