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Brief Report
April 20, 2020

Association of Dermatomyositis Sine Dermatitis With Anti–Nuclear Matrix Protein 2 Autoantibodies

Author Affiliations
  • 1Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 2Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 3Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 4Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 5Department of Neurology, Matsudo City General Hospital, Chiba, Japan
  • 6Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan
  • 7Department of Neurology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
  • 8Department of Rheumatology, Seirei Hamamatsu General Hospital, Shizuoka, Japan
  • 9Department of Neurology, JR Kyushu Hospital, Fukuoka, Japan
  • 10Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
  • 11Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  • 12Department of Neurology, Ageo Central General Hospital, Saitama, Japan
  • 13Department of Neurology, Kobe City Medical Center General Hospital, Hyogo, Japan
  • 14Department of Neurology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
  • 15Department of General Medicine, Toyooka Hospital, Hyogo, Japan
  • 16Department of Neurology, Otemae Hospital, Osaka, Japan
  • 17Department of General Internal Medicine, Tenri Hospital, Nara, Japan
  • 18Department of Neurology, Tenri Hospital, Nara, Japan
  • 19Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
  • 20Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan
  • 21Laboratory of Cutaneous Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
JAMA Neurol. 2020;77(7):872-877. doi:10.1001/jamaneurol.2020.0673
Key Points

Question  Does dermatomyositis sine dermatitis exist, and if yes, what are the serologic features of patients with dermatomyositis sine dermatitis?

Findings  In this cohort study of 182 patients with dermatomyositis who were positive for dermatomyositis-specific autoantibodies and myxovirus resistance protein A expression in myofibers, 14 (8%) had dermatomyositis sine dermatitis. Anti–nuclear matrix protein 2 autoantibodies were significantly associated with dermatomyositis sine dermatitis.

Meaning  Dermatomyositis sine dermatitis does exist and is significantly associated with anti–nuclear matrix protein 2 autoantibodies.


Importance  Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted.

Objective  To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features.

Design, Setting, and Participants  This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months.Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis.Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation–associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology.

Main Outcomes and Measures  Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy.

Results  Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti–transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001).

Conclusions and Relevance  Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

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