Julie J. Paik

The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy.

Introduction: To characterize cellular infiltrates in muscle biopsies from patients with anti‐3‐hydroxy‐3‐methyl‐gulatryl‐CoA reductase (HMGCR)‐associated myopathy. Methods: Biopsies from 18 anti‐HMGCR myopathy and 7 control dermatomyositis patients were analyzed. Results: CD4+ and CD8+ T‐cells were scattered within the endomysium in 50% of anti‐HMGCR biopsies. All anti‐HMGCR biopsies included increased endomysial and/or perivascular CD163+ M2 macrophages; CD11c+ M1 macrophages were present in 18.8%. CD123+ plasmacytoid dendritic (PD) cells were observed within the endomysium and perivascular spaces in 62.5% of anti‐HMGCR biopsies. Membrane attack complex was deposited on endothelial cells in 50% and on the sarcolemma of nonnecrotic muscle fibers in 85.7% of anti‐HMGCR cases. Major histocompatibility complex class I antigen was up‐regulated in 87.5% of the anti‐HMGCR cases. Conclusions: In addition to necrosis, scattered CD4+, CD8+, and PD cells are characteristic of anti‐HMGCR myopathy. Predominant M2 polarization suggests infiltrating macrophages are more likely to be involved with tissue repair than destruction. Muscle Nerve, 2015. Muscle Nerve 52: 189–195, 2015

Longitudinal Course of Disease in a Large Cohort of Myositis Patients With Autoantibodies Recognizing the Signal Recognition Particle.

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.

The co-existence of myasthenia gravis in patients with myositis: A case series

OBJECTIVE Myositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients. METHODS We identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features. RESULTS All 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%) patients. High-dose steroids were associated with worsening weakness in 2/6 (33%) patients. CONCLUSIONS Prominent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis-MG overlap, high-dose steroids may exacerbate symptoms and pyridostigmine may play an important therapeutic role.

Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity

Objectives The aims of this study were to define the pattern of muscle involvement in patients with immune-mediated necrotising myopathy (IMNM) relative to those with other inflammatory myopathies and to compare patients with IMNM with different autoantibodies. Methods All Johns Hopkins Myositis Longitudinal Cohort subjects with a thigh MRI (tMRI) who fulfilled criteria for IMNM, dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) or clinically amyopathic DM (CADM) were included in the study. Muscles were assessed for intramuscular and fascial oedema, atrophy and fatty replacement. Disease subgroups were compared using univariate and multivariate analyses. Patients with IMNM with anti-signal recognition particle (SRP) autoantibodies were compared with those with IMNM with anti-HMG-CoA reductase (HMGCR) autoantibodies. Results The study included 666 subjects (101 IMNM, 176 PM, 219 DM, 17 CADM and 153 IBM). Compared with DM or PM, IMNM was characterised by a higher proportion of thigh muscles with oedema, atrophy and fatty replacement (p<0.01). Patients with IMNM with anti-SRP had more atrophy (19%, p=0.003) and fatty replacement (18%, p=0.04) than those with anti-HMGCR. In IMNM, muscle abnormalities were especially common in the lateral rotator and gluteal groups. Fascial involvement was most widespread in DM. Fatty replacement of muscle tissue began early during the course of disease in IMNM and the other groups. An optimal combination of tMRI features had only a 55% positive predictive value for diagnosing IMNM. Conclusions Compared with patients with DM or PM, IMNM is characterised by more widespread muscle involvement. Anti-SRP-positive patients have more severe muscle involvement than anti-HMGCR-positive patients.

A longitudinal cohort study of the anti-synthetase syndrome: Increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies

Objective The aim was to study the prevalence, rate of appearance and severity of clinical features in patients with different anti-synthetase syndrome (ASyS) autoantibodies. Methods All Johns Hopkins Myositis Longitudinal Cohort subjects positive for any ASyS autoantibodies were included. Clinical information, including symptoms, signs, strength, creatine kinase concentrations and pulmonary function tests, were prospectively collected. The standardized mortality and cancer rates and the rate of appearance and intensity of the different organ manifestations were assessed using univariate and multivariate analysis and compared between ASyS autoantibodies. Results One hundred and twenty-four (73.4%) patients were positive for anti-Jo1, 23 (13.6%) for anti-PL12, 16 for anti-PL7 (9.5%) and 3 (1.8%) for anti-EJ or anti-OJ, respectively. The mean length of follow-up was 4.1 years. Anti-PL12 was more frequent in black subjects. Anti-PL12 and anti-PL7 were associated with more prevalent and severe lung involvement, often without muscle involvement. Anti-Jo1 displayed more severe muscle involvement compared with anti-PL12 patients. Concurrent anti-Ro52 was more prevalent in anti-Jo1 patients and was associated with earlier development of mechanics hands, DM-specific skin findings and arthritis. Independent of ASyS antibody status, black patients demonstrated more severe lung involvement than white patients. There was no significant increase in mortality or cancer risk in ASyS patients compared with the general US population. Conclusion Different ASyS autoantibodies are associated with phenotypically distinct subgroups within the ASyS spectrum. Anti-PL7 and anti-PL12 are characterized by more severe lung involvement, whereas anti-Jo1 is associated with more severe muscle involvement. Black race is a major prognostic factor associated with lung disease severity.

Spectrum of Muscle Histopathologic Findings in Forty‐Two Scleroderma Patients With Weakness

To determine if distinct muscle pathologic features exist in scleroderma subjects with weakness.

Statin-Induced Anti-HMGCR-Associated Myopathy.

In addition to self-limited myotoxicity, statins have recently been shown to trigger an immune-mediated necrotizing myopathy (IMNM), which is distinguished from polymyositis (PM) and dermatomyositis (DM) by the absence of primary inflammation on muscle biopsy. Previously, we have shown that patients

Independent Association of Severity of Muscle Weakness With Disability as Measured by the Health Assessment Questionnaire Disability Index in Scleroderma

To determine whether the presence and degree of muscle weakness in scleroderma is associated with disability.

Severity of muscle weakness independently associates with disability as measured by the Health Assessment Questionnaire‐Disability Index (HAQ‐DI) in scleroderma

To determine whether the presence and degree of muscle weakness in scleroderma is associated with disability.

Myopathy in scleroderma, its identification, prevalence, and treatment: lessons learned from cohort studies.

Purpose of reviewThis review discusses the characterization of myopathy in scleroderma with a focus on new developments in imaging, biomarkers, and therapy, and details several current reports and several seminal reports prior to 2012. Recent findingsIn the past year, studies have shown that MRI techniques highlight the importance of muscle edema in scleroderma, and that aldolase may be a useful biomarker to predict incident myopathy. When compared to studies preceding 2012, both the current and prior reports too often fail to account for the full spectrum of muscle disease in scleroderma. There remain no uniform classification criteria that are routinely integrated into clinical research reports. Thus, important questions remain to be answered, including risk factors for developing myopathy, optimal screening and diagnostic strategies, and efficacious therapies. But, just as important is the priority to systematically define what the true entity(ies) of myopathy is in scleroderma. SummaryScleroderma myopathy is a heterogeneous group of muscle disorders among patients with underlying scleroderma which requires robust studies to clarify the full spectrum of disease.