Anti-HMGCR myositis is usually a chronic disease requiring long-term immunosuppression. Although younger patients had more severe disease and a worse prognosis than older patients, they did not have evidence of a known co-existing muscular dystrophy to explain their persistent, and sometimes progressive, muscle weakness.

Objective Patients with immune-mediated necrotizing myopathy (IMNM) often have autoantibodies recognizing the signal recognition particle (SRP) or HMG-CoA reductase (HMGCR). Here, we studied a cohort of anti-SRP patients to identify factors associated with disease severity and clinical improvement; we also compared the severity of weakness in those with anti-SRP versus anti-HMGCR autoantibodies. Methods All anti-SRP patients in the Johns Hopkins Myositis Cohort from 2002 to 2015 were included. Longitudinal information regarding proximal muscle strength, creatine kinase (CK) levels, and immunosuppressive therapy were recorded at each visit. Univariate and multivariate multilevel regression models were used to assess prognostic factors influencing recovery. Strength in the anti-SRP patients was compared to strength in 49 previously described anti-HMGCR subjects. Results Data from 37 anti-SRP patients and 380 total clinic visits was analyzed. Younger age at onset was associated with more severe weakness at the first visit (p=0.02) and all subsequent visits (p=0.002). Only 50% of patients reached near-full or full strength after 4 years of treatment and most of these continued to have elevated CK levels. Rituximab appeared to be effective in 13 of 17 anti-SRP patients. Anti-SRP patients were significantly weaker than those with anti-HMGCR autoantibodies (−1.3 strength points, p=0.001). Conclusions Younger age at onset is associated with more severe weakness in anti-SRP myositis. Furthermore, even among anti-SRP patients whose strength improved with immunosuppression, most had ongoing disease activity as demonstrated by elevated CK levels. Finally, anti-SRP patients were significantly weaker than anti-HMGCR patients, providing evidence that these autoantibodies are associated with distinct forms of IMNM.

Objectives Dermatomyositis (DM) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP-2 often presented with especially severe weakness. The aim of this study was to characterize clinical features associated with anti-NXP-2 autoantibodies. Methods 235 DM patients underwent testing for anti-NXP-2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti-NXP-2-positive subjects was compared with the number expected in the general population. Results 56 (23.8%) of the DM patients were anti-NXP-2-positive. There was no significant difference in the prevalence of proximal limb weakness in patients with and without anti-NXP-2. In contrast, anti-NXP-2-positive patients had more prevalent weakness in the distal arms (35% vs. 20%, p=0.02), distal legs (25% vs. 8%, p<0.001), and neck (48% vs. 23%, p<0.001). Anti-NXP-2-positive subjects were also more likely to have dysphagia (62% vs. 35%, p<0.001), myalgia (46% vs. 25%, p=0.002), calcinosis (30% vs. 17%, p=0.02) and subcutaneous edema (36% vs. 19%, p=0.01) than anti-NXP-2-negative patients. Five (9%) anti-NXP-2-positive subjects had cancer-associated myositis, representing a 3.68-fold increased risk (95% confidence interval 1.2-8.6) compared to the expected prevalence in the general population. Conclusions In DM, anti-NXP-2 autoantibodies are associated with subcutaneous edema, calcinosis, and a severe muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti-NXP-2 positive patients have an increased risk of cancer, we suggest they should undergo comprehensive cancer screening.

The rs-fcMRI functional connectivity changes within (intranetwork) and between (internetwork) resting state networks occur after acute ON, indicating immediate cortical responses to focal inflammatory demyelination. Thus, focal white matter injury in the central nervous system acutely results in widespread network alterations that may lead to functional neurologic changes seen in MS.