Systematic retrospective study of 64 patients with anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy.

To the Editor: Dermatomyositis (DM) is an autoimmune myopathy associated with the presence of a specific skin rash and characteristic morphologic features, including perifascicular pathology without myofiber necrosis. However, the clinical and morphologic spectrum of DM remains heterogeneous. It is now recognized that DM-specific autoantibodies are useful in defining more homogeneous subsets of patients with DM.1Benveniste O. Stenzel W. Allenbach Y. Advances in serological diagnostics of inflammatory myopathies.Curr Opin Neurol. 2016; 29: 662-673Crossref PubMed Scopus (54) Google Scholar The anti-Mi2 antibody was discovered more than 40 years ago; nonetheless, few studies have described its phenotype, and these have included only a limited number of patients.2Hamaguchi Y. Kuwana M. Hoshino K. et al.Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study.Arch Dermatol. 2011; 147: 391-398Crossref PubMed Scopus (203) Google Scholar In this study, we aim to characterize the anti-Mi2 DM phenotype with a focus on the cutaneous and muscular features, including a myopathologic description of the skeletal muscle biopsies, and evaluate its association with cancer. This was an observational, multicenter study (16 medical centers) from July 2013 through January 2017. Anti-Mi2+ and anti-Mi2- (control) patients with DM were included if they presented with (1) DM skin rash as defined by the European NeuroMuscular Center3Mammen A.L. Allenbach Y. Stenzel W. Benveniste O. ENMC 239th Workshop Study Group. 239th ENMC International Workshop: classification of dermatomyositis, Amsterdam, The Netherlands, 14-16 December 2018.Neuromuscul Disord. 2020; 30: 70-92Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and/or Sontheimer4Sontheimer R.D. Dermatomyositis: an overview of recent progress with emphasis on dermatological aspects.Dermatol Clin. 2002; 20: 387-408Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar criteria and (2) DM-specific antibodies (anti-Mi2, anti-NXP2, anti-MDA5, anti-TIF1γ, or anti-SAE) and/or myopathologic features of DM (for seronegative patients) according to the European NeuroMuscular Center criteria.3Mammen A.L. Allenbach Y. Stenzel W. Benveniste O. ENMC 239th Workshop Study Group. 239th ENMC International Workshop: classification of dermatomyositis, Amsterdam, The Netherlands, 14-16 December 2018.Neuromuscul Disord. 2020; 30: 70-92Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar All muscle biopsy samples from the Pitié-Salpêtrière Hospital (anti-Mi2+ patients with DM, n = 20; control patients, n = 32) were reviewed. Sixty-four anti-Mi2+ patients with DM were included. The median age at diagnosis was 55.5 years (first and fourth quartile, 38.1-65.8), and patients were mainly females (60.9%; n = 39/64). Comparison of features of anti-Mi2+ patients with DM and those of control patients (n = 55) is shown in Table I. Anti-Mi2+ patients with DM presented more frequently with a classic DM skin rash (including Gottron papules/sign and/or heliotrope rash and/or periungual erythema and/or violaceous rash including Holster sign) without additional skin changes such as calcinosis, ulcers, panniculitis, and/or mechanic hands (82.8% vs 45.3%; P = .0004) (Table I).Table IComparison of cutaneous, muscular, extracutaneous, and extramuscular manifestations of anti-Mi2+ and anti-Mi2− patientsFeaturesAnti-Mi2+ DM, n (%) n = 64Anti-Mi2− DM, n (%) n = 55Fisher's test, n (%)P valueCutaneous features Alopecia1/42 (2.4)7/55 (12.7).13 Calcinosis cutis1/56 (1.8)6/55 (10.9).06 Panniculitis2/42 (4.7)3/55 (5.5)>.99 Cutaneous ulceration2/56 (3.6)10/55 (18.2).02 Mechanic hands6/56 (10.7)7/55 (12.7).78 Heliotrope rash41/64 (64.1)34/55 (61.8).8 Gottron papules/sign38/53 (71.7)21/55 (38.2).0005 Periungual erythema36/56 (64.3)25/55 (45.5).05 Holster sign12/55 (21.8)2/55 (3.6).008Muscular features Myalgia15/23 (65.2)48/54 (89).02 Proximal weakness61/64 (95.3)49/55 (89.1).35 Severe weakness (MRC score, ≤3)29/54 (53.7)35/55 (66).02 Elevated CK level58/64 (90.6)46/55 (83.6).28 CK level (IU/L)∗The CK level values are presented as mean (range).3748 (1159-8799)1680 (893-5818).23 Myopathic EMG32/37 (86.5)34/42 (81).56 Abnormal muscle MRI†Muscle MRI abnormalities are defined as sequence T1 inversion-recuperation or fat-saturated gadolinium-enhanced T2-weighted or gadolinium-enhanced T1-weighted hypersignals.20/33 (62.5)30/53 (56.6).87T2 hypersignal15/17 (88.2)23/31 (74.2).46T1 fat replacement6/17 (35.3)9/25 (36)>.99Extracutaneous and extramuscular features Raynaud phenomenon8/63 (12.7)12/54 (22.2).26 Arthritis/arthralgia17/63 (27)23/55 (41.8).13 Dyspnea1/10 (10)31/52 (59.6).01 ILD13/34 (38.2)10/52 (19.2).08 FEV < 70%2/11 (18.2)9/47 (19.2)>.99 FCV < 70%1/24 (4.2)7/46 (15.2).25 DLCOc < 70%3/22 (13.6)14/23 (60.9).002 Myositis specific antibodies64/64 (100)20/55 (36.4)<.0001Anti-Mi264/64 (100)0/55 (0)<.0001Anti-MDA5—9/37 (24.32)—Anti-NXP2—3/31 (9.68)—Anti-SAE1/2—3/31 (9.68)—Anti-TIF1γ—5/32 (13.51)—DLCOc, Corrected carbon monoxide diffusion capacity; CK, creatine kinase; DM, dermatomyositis; EMG, electromyogram; FCV, forced vital capacity; FEV, forced expiratory volume; ILD, interstitial lung disease (defined on chest computed tomography scan); MRC, Medical Research Council; MRI, magnetic resonance imaging.∗ The CK level values are presented as mean (range).† Muscle MRI abnormalities are defined as sequence T1 inversion-recuperation or fat-saturated gadolinium-enhanced T2-weighted or gadolinium-enhanced T1-weighted hypersignals. Open table in a new tab DLCOc, Corrected carbon monoxide diffusion capacity; CK, creatine kinase; DM, dermatomyositis; EMG, electromyogram; FCV, forced vital capacity; FEV, forced expiratory volume; ILD, interstitial lung disease (defined on chest computed tomography scan); MRC, Medical Research Council; MRI, magnetic resonance imaging. All anti-Mi2+ patients with DM except 1 (amyopathic) had proximal muscle weakness (Table I), and in more than half of these patients, muscle weakness was severe (Medical Research Council 5 scale, ≤3). Consistent with the presence of high creatine kinase levels (Table I), anti-Mi2+ patients with DM had increased myofiber necrosis (90% vs 26% in control patients; P < .0001) encountered in both the perifascicular and centrofascicular areas. A perifascicular atrophy was observed in all anti-Mi2+ patients with DM. Compared with the age- and sex-matched expected cancer rate in the general French population, the anti-Mi2+ patients with DM had an increased risk of cancer, with a standardized incidence ratio of 5.1 (95% confidence interval [CI]: 3.0-8.6) (P < .001). The median time between DM diagnosis and malignancy diagnosis was 61.5 days [95% CI: -105.8 to 237.5]. All but 1 of the anti-Mi2+ patients with DM who had cancer-associated myositis were older than 50 years. Patients with malignancy had a worse prognosis with higher mortality rate compared with patients without cancer (P = .008) (Fig 1). Although patients with DM with anti–TIF1-γ, anti-MDA5, anti-SAE, and anti-NXP2 may display distinct cutaneous features in addition to the classic DM skin rash,5Wolstencroft P.W. Fiorentino D.F. Dermatomyositis clinical and pathological phenotypes associated with myositis-specific autoantibodies.Curr Rheumatol Rep. 2018; 20: 28Crossref PubMed Scopus (32) Google Scholar we observed that anti-Mi2+ patients with DM present a classic DM skin rash more frequently. For the first time, to our knowledge, we showed that anti-Mi2+ patients with DM present extracutaneous characteristics, including a necrotizing myositis and an increased risk of malignancy. These findings strengthen the importance of DM-specific antibodies to delineate more homogeneous DM phenotypes. We are indebted to Francis Gaches, MD, Céline Anquetil, MD, MSci, Elisabeth Comby, MD, Groupe d’Etudes des Maladies Systémiques en Dermatologie, Amicale des Jeunes Internistes, and Société Nationale Française de Médecine Interne. Comment on “Systematic retrospective study on 64 patients anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy”Journal of the American Academy of DermatologyVol. 83Issue 6PreviewTo the Editor: We read with great interest the study by Monseau et al1 on the clinical characteristics of patients with anti-Mi2 dermatomyositis (DM). The importance of DM-specific autoantibodies (Abs) to delineate more homogeneous DM phenotypes is a conclusion that we share with our French, Canadian, and German colleagues. We would like to comment on the unexpected finding that patients with anti-Mi2 DM were found to have an increased risk of malignancies compared to the age- and sex-matched control individuals in the general French population. Full-Text PDF