封入体筋炎

IMPORTANCE: Preliminary evidence suggests that intravenous immune globulin (IVIG) may be valuable as an add-on treatment in newly diagnosed idiopathic inflammatory myopathies (IIMs), but a randomized clinical trial is warranted. OBJECTIVE: To determine whether 3 cycles of add-on IVIG lead to superior improvement, with acceptable safety, in patients with newly diagnosed IIMs treated with high-dose prednisone (1 mg/kg/d; maximum 80 mg/d). DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomized, placebo-controlled clinical trial conducted at a tertiary referral center for IIM between September 2021 and September 2025, with the primary end point at week 12. Adult patients with newly diagnosed IIMs, without (or with limited) prior immunosuppressive treatment, were assessed for inclusion; of 94 assessed, 50 were excluded or declined participation. INTERVENTION: All patients initiated treatment with standard of care high-dose prednisone and were assigned in a 1:1 ratio to receive add-on IVIG (2.0 g/kg body weight) or placebo at 0, 4, and 8 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the Total Improvement Score (TIS) at 12 weeks: a weighted composite score from 6 measures reflecting change in myositis activity over time. Secondary outcomes included moderate (TIS ≥40) and major (TIS ≥60; post hoc analysis) improvement, time to reach improvement, and safety outcomes. RESULTS: Of 44 adult patients with newly diagnosed IIMs included, 42 reached a primary end point (mean [SD] age, 58.7 [15.2] years; 21 [50%] female); 23 received IVIG and 19 received placebo. The mean TIS at 12 weeks was 60.0 (95% CI, 52.6-67.4) in the IVIG group and 42.5 (95% CI, 30.6-54.4) in the placebo group (P = .01). Moderate and major improvement were achieved in 21 participants in the IVIG group (91%; 95% CI, 79-100) vs 10 in placebo (53%; 95% CI, 28-78; P = .01) and 16 in the IVIG group (70%; 95% CI, 49-90) vs 5 in placebo (26%; 95% CI, 5-48; P = .005), respectively. The median time to moderate response was 4 (95% CI, 4-8) weeks in the IVIG group and 12 (95% CI, 4-12) weeks in the placebo group (P = .005). One asymptomatic deep venous thrombosis was found in the IVIG group. CONCLUSIONS AND RELEVANCE: Adult patients with newly diagnosed IIMs treated with IVIG in addition to standard high-dose prednisone showed greater and faster improvement compared to patients who received standard high-dose prednisone. TRIAL REGISTRATION: EudraCT Identifier: EUCTR2020-001710-37-NL.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) have historically been viewed to cause painless weakness and are therefore poorly understood. We aimed to report pain characteristics in patients with IIMs and estimate the contributions of fibromyalgia and common painful comorbidities to pain intensity. METHODS: An international electronic survey was circulated to individuals who self-reported IIMs and pain attributable to myositis. Questions included pain characteristics, perceptions of provider understanding of their pain, comorbidities, and the Fibromyalgia Survey Questionnaire. Hierarchical multiple linear regression was used to examine the contribution of fibromyalgia symptom burden and other painful comorbidities to pain intensity (0-10 visual analog scale), adjusting for age, sex, country, IIM subtype, and duration. RESULTS: A total of 552 participants (mean age 58.0 years; 81.3% female) with pain attributable to myositis were included. Mean pain intensity was 4.6 out of 10. Most participants reported pain starting near diagnosis. The most painful areas were back, neck, and upper legs. The majority reported that their pain was not well understood by their care team. Approximately 60% met the fibromyalgia criteria and reported higher, more persistent, and widespread pain. Pain intensity was the highest in overlap myositis and lowest in inclusion body myositis. Fibromyalgia symptom burden explained 20% of variance in pain intensity, whereas osteoarthritis, degenerative disc disease, and diabetic neuropathy were not significant contributors. CONCLUSION: Most patients with self-reported IIMs experience moderate, persistent pain that is not well understood by their care team. Fibromyalgia symptom burden accounted for a substantial proportion of pain variability, suggesting an important nociplastic component, though additional mechanisms likely contribute.

Inclusion body myositis (IBM) is considered an inflammatory myopathy with a degenerative counterpart that is generally refractory to standard immunotherapy. We describe the case of a 47-year-old lady who had a long history of rheumatoid arthritis (RA) and subsequently developed weakness in her limbs. A muscle biopsy revealed typical features of IBM along with vasculitis. She was initiated on pulse corticosteroids followed by rituximab. The patient made a steady and marked recovery in both muscle weakness and inflammatory arthritis. Rare cases of IBM in patients with RA with favorable responses to immunotherapy have been reported before. This case demonstrates the importance of identifying coexisting autoimmune disorders and executing a long-term immunomodulatory plan.

BACKGROUND: Several idiopathic inflammatory myopathies (IIM), originally classified under polymyositis, evolved into distinct entities. Herein, we describe clinical features and treatment outcomes of a potentially novel clinico-histopathological entity: myositis with nemaline rods (MNR). METHODS: We performed retrospective chart review of the Mayo Clinic electronic medical records to identify patients with nemaline rods and muscle inflammation on biopsy, not fitting into any IIM subgroup, and extracted clinical and laboratory data. Additional immunohistochemical studies were performed on muscle biopsies. RESULTS: Eleven patients were identified, with mean age at onset 61.8 years (SD = 9.8), seven were female. MNR had a distinctive phenotype with rapidly progressive weakness, predominantly affecting swallowing, axial, and proximal limb muscles, often with prominent myalgia. No patients had monoclonal gammopathy. Creatine kinase levels were elevated in 73% of patients. Muscle histopathology revealed nemaline rods in non-atrophic and atrophic fibers. Inflammation was often endomysial, where both CD4+ and CD8+ T cells invaded nonnecrotic muscle fibers. A significant proportion of CD8+ T cells were KLRG1+. Of patients with follow-up, 6/8 responded to immunosuppressive treatment with some going into remission. Although MNR shares features with sporadic late-onset nemaline myopathy (SLONM) and inclusion body myositis (IBM), it has important distinctions. Unlike SLONM, MNR shows endomysial inflammation and no monoclonal protein; unlike IBM, MNR exhibits distinct clinical features, rapid progression, and responsiveness to immunotherapy. CONCLUSIONS: MNR is associated with a unique combination of clinical and histopathological features, responding well to treatment in most cases. Future studies are needed to explore underlying mechanisms and identify serological biomarkers.

The progressive muscle disease inclusion body myositis (IBM) is characterized, amongst others, by inflammatory features and protein accumulation in skeletal muscle fibers. One of the proteins that accumulates in perinuclear and peripheral regions of muscle fibers is cytosolic 5'-nucleotidase 1A (cN1A), the target of anti-cN1A autoantibodies, which are found in many IBM patients. To shed more light on potential pathogenic aspects of IBM, we identified post-translational modifications of cN1A in human skeletal muscle. Immunoaffinity-purification followed by mass spectrometry resulted in the identification of three monomethylation sites, K178, R223, and K243. Single amino acid substitutions of each of these methylation sites did not detectably affect the accumulation of cN1A in perinuclear regions of cultured human cell lines. Two of these monomethylation sites, R223 and K243, are located within one of the previously identified major linear epitope regions of cN1A. Synthetic peptides, corresponding to aa 219 - aa 247, were used to investigate the effect of monomethylation on the antigenicity of this epitope by ELISA. The results showed that the simultaneous monomethylation of R223 and K243 may enhance its recognition by IgG autoantibodies. We conclude that cN1A contains at least three amino acids that can be monomethylated and that monomethylation may affect its autoantigenicity.