The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

Abstract

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron’s papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with the anti-synthetase antibody had higher frequencies of interstitial lung disease, arthralgia, and mechanic’s hands, and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud’s phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes.

Cutaneous Manifestations in Dermatomyositis: Key Clinical and Serological Features—a Comprehensive Review

“…A recent Brazilian study showed that anti-Mi-2-positive DM patients are significantly more likely to have photosensitivity and the shawl sign by univariate analysis but that, by multivariate analysis, the anti-Mi-2 antibody was associated only with photosensitivity [25]. According to a North American collaborative study, JDM patients with the anti-Mi-2 antibody showed the V-neck sign, the shawl sign, and cuticular overgrowth significantly less than adult DM patients did [26]. …”

“…In a US cohort, generalized lipodystrophy was reported to be associated with these antibodies [33]. In a subsequent report of US cohort, anti-TIF1γ/α antibody-positive patients showed classic JDM features, including Gottron papules, heliotrope and malar rashes, periungual abnormalities, photosensitivity, linear extensor erythema, cuticular overgrowth, V-neck sign, shawl sign, lipodystrophy, and erythroderma [26].…”

“…Juvenile-onset patients with anti-ARS show mechanic's hands less frequently than adult-onset patients (32 vs 71 %) [26].…”

Idiopathic Inflammatory Myopathies: an Update on Classification and Treatment with Special Focus on Juvenile Forms

“…Anti-p155/140 and anti-MJ autoantibodies are the most frequent MSAs in JIIM and are primarily associated with JDM [17]. In particular, anti-p155/140 autoantibodies are linked to photosensitive skin rash, including malar rash, Vsign, shawl-sign rash and linear extensor erythema.…”

The Disappearance of a Hepatic Mass in Anti-Synthetase Syndrome

“…(1)(2)(3) A number of autoantibodies, called myositis-specific autoantibodies (MSA), have been described in IIM. (4,5) The presence of MSA is a key feature for diagnosis of clinically distinguishable IIM subsets (polymyositis (PM), dermatomyositis (DM), inclusion body myositis, and myositis associated with malignancy and other connective tissue diseases).…”