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Anti-Ku antibody-positive systemic sclerosis and idiopathic inflammatory myopathies overlap syndrome in children: a report of two cases and a review of the literature

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Abstract

The occurrence of anti-Ku antibody-positive idiopathic inflammatory myopathy (IIM) in pediatric patients is rare, and therefore, the clinical phenotypes of this disease in such patients remain obscure. We herein report two cases of Japanese female pediatric patients with anti-Ku antibody-positive IIM. One case was unique in that it was complicated by pericardial effusion. Another patient had severe and refractory myositis with immune-mediated necrotizing myopathy. In addition, we reviewed literatures involving a total of 11 pediatric patients with anti-Ku antibody-positive IIM. The median age of the patients was 11 years, and most of them were girls. Skin rash, including erythematous nodules, malar rash, multiple brownish plaques, butterfly rash, heliotrope rash, periorbital edema, and Gottron’s papules, was observed in 54.5% of the patients, scleroderma in 81.8%, and skin ulcer in 18.2%. Their serum creatine kinase level ranged from 504 to 10,840 IU/L. Furthermore, joint involvement was observed in 91% of the patients, interstitial lung disease in 18.2%, and esophageal involvement in 9.1%. All patients were treated with corticosteroids in combination with immunosuppressants. Pediatric patients with anti-Ku antibody-positive IIM had unique characteristics compared to adult patients. Skin manifestations, joint involvement and elevation of serum CK levels were more common in children than in adults. In contrast, ILD and esophageal involvement were less common in children than in adults. Although pediatric cases of anti-Ku antibody-positive IIM are rare, patients with IIM need to be tested for the presence of anti-Ku antibodies.

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Abbreviations

IIM :

Idiopathic inflammatory myopathy

MSA :

Myositis-specific autoantibodies

MAAs :

Myositis-associated autoantibodies

SLE :

Systemic lupus erythematosus

ILD :

Interstitial lung disease

CK :

Creatine kinase

ANA :

Antinuclear antibody

MRI :

Magnetic resonance imaging

PSL :

Prednisolone

MTX :

Methotrexate

MPT :

Methylprednisolone pulse therapy

MMF :

Mycophenolate mofetil

LDH :

Lactate dehydrogenase

AST :

Aspartate aminotransferase

MAC :

Membrane attack complex

IVIG :

Intravenous immune globulin

Tac :

Tacrolimus

References

  1. Lieber MR, Ma Y, Pannicke U, Schwarz K (2004) The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination. DNA Repair 3:817–826

    Article  CAS  PubMed  Google Scholar 

  2. Schild-Poulter C, Haché RJG, Soubeyrand S (2004) Ku antigen: a versatile DNA binding protein with multiple cellular functions. In: Parisi V, De Fonzo V, Aluffi-Pentini F (eds) Recent research developments in dynamical genetics, Research Signpost, Transworld Research Network, p 257–284

  3. Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M (1981) Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest 68:611–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Betteridge Z, McHugh N (2016) Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med 280:8–23

    Article  CAS  PubMed  Google Scholar 

  5. Birdi N, Laxer RM, Thorner P, Fritzler MJ, Silverman ED (1993) Localized scleroderma progressing to systemic disease. case report and review of the literature. Arthritis Rheum 36:410–415

    Article  CAS  PubMed  Google Scholar 

  6. Nitta Y, Muramatsu M (2000) A juvenile case of overlap syndrome of systemic lupus erythematosus and polymyositis, later accompanied by systemic sclerosis with the development of anti-Scl 70 and anti-Ku antibodies. Pediatr Dermatol 17:381–383

    Article  CAS  Google Scholar 

  7. Azanmene B, Badot V, Verlinden S et al (2012) Isolated anti-Ku antibody in scleroderma-myositis overlap syndrome: the histo-pathological patern. J Transl Med 10(Suppl 3):P57

    Article  PubMed Central  Google Scholar 

  8. Kishi T, Miyamae T, Morimoto R et al (2015) Childhood-onset Anti-Ku antibody-positive generalized morphea with polymyositis: a Japanese case study. Pediatr Dermatol 32:e224–e225

    Article  PubMed  Google Scholar 

  9. Kaur N, Wong M (2016) CGRA10: a rare case of anti-Ku antibodies positive systemic lupus erythematosus and juvenile dermatomyositis overlap in a paediatric patient. Intern Med J 46:32

    Article  Google Scholar 

  10. Khaosut P, Castagno S, Aluko A, Al-Obaidi M (2017) Anti-KU antibodies in two paediatric cases with juvenile dermatomyositis-scleroderma overlap: why is it important to know? Rheumatology 56:24

    Article  Google Scholar 

  11. Loo RJ, Nocton JJ, Harmelink MM, Chiu YE (2020) Anti-Ku antibody-positive systemic sclerosis-polymyositis overlap syndrome in an adolescent. Pediatr Dermatol 37:960–961

    Article  PubMed  Google Scholar 

  12. Cotter C, Rudd E, Williamson E, Philippidou M, Tewari A (2022) Anti-Ku-positive juvenile dermatomyositis. Clin Exp Dermatol 47:425–427

    Article  CAS  PubMed  Google Scholar 

  13. Wu W, Guo L, Fu Y, Wang K, Zhang D, Xu W, Chen Z, Ye S (2021) Interstitial lung disease in Anti-MDA5 positive dermatomyositis. Clin Rev Allergy Immunol 60:293–304

    Article  CAS  PubMed  Google Scholar 

  14. Casal-Dominguez M, Pinal-Fernandez I, Derfoul A, Graf R, Michelle H, Albayda J, Tiniakou E, Adler B, Danoff SK, Lloyd TE, Christoper-Stine L, Paik JJ, Mammen AL (2021) The phenotype of myositis patients with anti-Ku autoantibodies. Semin Arthritis Rheum 51:728–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Campochiaro C, De Luca G, De Santis M (2021) Anti-Ku syndrome with elevated CK: association with myocardial involvement in systemic sclerosis. Ann Rheum Dis 80:e113

    Article  PubMed  Google Scholar 

  16. Shah M, Shinjo SK, Day J, Gupta L (2023) Cardiovascular manifestations in idiopathic inflammatory myopathies. Clin Rheumatol. https://doi.org/10.1007/s10067-023-06599-4. Online ahead of print

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Acknowledgements

We would like to thank Dr. Maho Hatano and Dr. Yuko Hayashi for a helpful discussion. We would also like to thank Dr. Ichizo Nishino for helpful suggestions for immunological findings related to muscle biopsy. Immunohistochemical study of muscle biopsy specimen was supported by an Intramural Research Grant (2–5, 5-6) for Neurological and Psychiatric Disorders of the NCNP.

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Authors and Affiliations

  1. Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata-Shi, Osaka, 573-1010, Japan

    Saki Kanda, Yoshitaka Nakamura, Ryosuke Matsuno & Kazunari Kaneko

  2. Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Asami Shimbo, Shuya Kaneko, Hitoshi Irabu & Masaki Shimizu

Authors
  1. Saki Kanda
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  2. Asami Shimbo
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  3. Yoshitaka Nakamura
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  4. Ryosuke Matsuno
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  5. Shuya Kaneko
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  6. Hitoshi Irabu
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  7. Kazunari Kaneko
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Contributions

SK, AS, RM and M.S. wrote the manuscript; SK, AS, YN, RM, SK, HI, and MS collected data; and K.K. critically reviewed the manuscript and supervised the whole study process. All authors read and approved the final manuscript.

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Correspondence to Ryosuke Matsuno or Masaki Shimizu.

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Kanda, S., Shimbo, A., Nakamura, Y. et al. Anti-Ku antibody-positive systemic sclerosis and idiopathic inflammatory myopathies overlap syndrome in children: a report of two cases and a review of the literature. Clin Rheumatol 42, 3411–3417 (2023). https://doi.org/10.1007/s10067-023-06687-5

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  • DOI: https://doi.org/10.1007/s10067-023-06687-5

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