Michio Inoue1,2, Jantima Tanboon1,2, Shinya Hirakawa3, Hirofumi Komaki4, Takeshi Fukushima5, Hiroyuki Awano6, Takashi Tajima7, Kenji Yamazaki8, Ryutaro Hayashi9, Tatsuo Mori10, Kazumoto Shibuya11, Takahiko Yamanoi12, Hajime Yoshimura13, Tomohiro Ogawa14, Atsushi Katayama15, Fuminobu Sugai16, Yoichi Nakayama17, Satoko Yamaguchi18, Shinichiro Hayashi1,2, Satoru Noguchi1,2, Hisateru Tachimori3, Naoko Okiyama19, Manabu Fujimoto20,21, Ichizo Nishino1,2. 1. Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. 2. Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan. 3. Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan. 4. Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan. 5. Department of Neurology, Matsudo City General Hospital, Chiba, Japan. 6. Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan. 7. Department of Neurology, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 8. Department of Rheumatology, Seirei Hamamatsu General Hospital, Shizuoka, Japan. 9. Department of Neurology, JR Kyushu Hospital, Fukuoka, Japan. 10. Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan. 11. Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan. 12. Department of Neurology, Ageo Central General Hospital, Saitama, Japan. 13. Department of Neurology, Kobe City Medical Center General Hospital, Hyogo, Japan. 14. Department of Neurology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan. 15. Department of General Medicine, Toyooka Hospital, Hyogo, Japan. 16. Department of Neurology, Otemae Hospital, Osaka, Japan. 17. Department of General Internal Medicine, Tenri Hospital, Nara, Japan. 18. Department of Neurology, Tenri Hospital, Nara, Japan. 19. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 20. Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan. 21. Laboratory of Cutaneous Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan.
Abstract
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.
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-MDA5DM, 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.
Authors: Jessica E Hoogendijk; Anthony A Amato; Bryan R Lecky; Ernest H Choy; Ingrid E Lundberg; Michael R Rose; Jiri Vencovsky; Marianne de Visser; Richard A Hughes Journal: Neuromuscul Disord Date: 2004-05 Impact factor: 4.296
Authors: Ingrid E Lundberg; Manabu Fujimoto; Jiri Vencovsky; Rohit Aggarwal; Marie Holmqvist; Lisa Christopher-Stine; Andrew L Mammen; Frederick W Miller Journal: Nat Rev Dis Primers Date: 2021-12-02 Impact factor: 52.329