[Establishing a predictive model for the activity of idiopathic inflammatory myopathy based on MRI and clinical features].

Objective: To analyze MRI and clinical characteristics of idiopathic inflammatory myopathy (IIM) activity and construct a prediction model. Methods: A retrospective analysis was conducted on 326 patients with IIM from December 2019 to December 2023 at General Hospital of Ningxia Medical University, including 112 males and 214 females, aged(53.7±15.3) years. According to histopathology and electromyography, they were divided into active phase group(n=86) and inactive phase group (n=240). The two groups were randomly divided into the training set and the verification set according to the ratio of 7∶3. The single factor analysis, least absolute shrinkage and selection operator (Lasso), random forest algorithm, and multivariate logistic regression model were used to screen the risk factors of IIM activity and construct a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the performance of prediction model. Results: There were significant differences in gender, age, T1 value, T2 value, creatine kinase-MB(CKMB), creatine kinase (CK) and lactate dehydrogenase (LDH) between the two groups(all P<0.05). Lasso and random forest algorithm screened 5 variables for analysis, age (λ=-0.009), T2 value (λ=-2.564), CKMB (λ=-0.256), CK (λ=-0.492), LDH (λ=-2.786) respectively. Multivariate logistic regression model showed that age (OR=1.603, 95%CI: 1.030-1.096), T2(OR=352.269, 95%CI: 13.303-9 328.053), CKMB (OR=2.470, 95%CI: 1.497-4.075), CK(OR=4.973, 95%CI: 2.583-9.575), LDH(OR=1 155.247, 95%CI: 152.387-8 757.954) were risk factors for active IIM patients. A prediction model nomograms were drawn with the above risk factors included. The area under the ROC curve (AUC) of the prediction model for the training set MRI combined with clinical indicators was higher than that of the clinical indicator model [0.914 (95%CI: 0.873-0.955) vs 0.901 (95%CI: 0.858-0.945), P<0.001], with sensitivity of 88.3% and 90.7%, and specificity of 81.7% and 75.0%, respectively. The AUC of the prediction model for the validation set MRI combined with clinical indicators was higher than that of the clinical model [0.982 (95%CI: 0.873-0.955) vs 0.934 (95%CI: 0.858-0.945), P<0.001], with sensitivity of 97.2% and 88.5%, and specificity of 100.0% and 92.3%, respectively. The calibration curves plotted in the training set and test set, respectively, fit well with the ideal curve. Conclusion: The nomogram model of MRI combined with clinical indicators can effectively predict the activity of IIM.

Case report: Multi-antibody-positive myasthenia gravis concomitant myositis associated with thymoma.

Myasthenia gravis (MG) and idiopathic inflammatory myopathy (IIM) are autoimmune diseases of the nervous system, and their main clinical manifestation is muscle weakness. The concurrent presence of both conditions in the same patient is clinically rare and easily missed. Here, we report the case of a 74-year-old woman who went to the doctor with fluctuating weakness of the limbs and muscle pain. By analyzing the patient's history and the results of repeated frequency electrical stimulation, chest computed tomography, thigh muscle magnetic resonance imaging, serum antibody detection, lymph node biopsy, etc., she was finally diagnosed with MG-concomitant IIM with squamous cell carcinoma of the thymus. Acetylcholine receptor antibody, titin antibody, ryanodine receptor antibody, anti-JO-1 antibody, and Ro-52 antibody tests were positive. MG-concomitant IIM is often associated with thymoma. The immunopathology mechanism may be different from that of pure MG or IIM, which needs further research.

Thyrotoxic periodic paralysis complicated by carbimazole-associated myositis.

A male of East Asian background in his 30s presented to the emergency department with acute onset global muscle weakness, elevated creatine kinase, profound hypokalaemia and hyperthyroidism. A diagnosis of thyrotoxic periodic paralysis was made and the myopathy resolved promptly with potassium replacement. However, 3 months after being commenced on carbimazole for hyperthyroidism, the patient developed myalgias without weakness associated with an elevated creatine kinase. The myositis panel was negative, while a muscle biopsy showed nonspecific, mild myopathic changes with minimal lymphocytic inflammation. As a change in therapy from carbimazole to propylthiouracil resulted in prompt symptom improvement and normalisation of serum creatine kinase levels, a presumptive diagnosis of carbimazole-induced myositis was made. Genetic testing for hereditary skeletal muscle channelopathies did not identify any gene of interest.

Management of bone health in idiopathic inflammatory myopathies: A two-center audit in the United Kingdom and Hong Kong.

BACKGROUND: Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. AIM: To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). METHODS: Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. RESULTS: Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). CONCLUSION: Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.

Anti-synthetase and myelodysplastic syndromes with deep morphea: an example of shared immunopathogenesis? A case-based review.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient.

Pathogenic mechanisms of disease in idiopathic inflammatory myopathies: autoantibodies as clues.

Idiopathic inflammatory myopathies (IIMs) encompass a spectrum of autoimmune diseases characterized by muscle inflammation and systemic involvement. This review aimed to synthesize current evidence on the clinical significance and pathogenic mechanisms underlying autoantibodies associated with IIMs. Autoantibodies targeting aminoacyl-tRNA synthetases (ARS) play a pivotal role in antisynthetase syndrome (ASS), highlighting associations with interstitial lung disease (ILD) and distinctive clinical features. Anti-Mi-2 antibodies in dermatomyositis (DM) are hallmarked by characteristic cutaneous manifestations and favorable prognostic outcomes. Conversely, anti-TIF1 antibodies are correlated with DM and a higher risk of malignancies, implicating CD8+ T cells in its pathogenesis. Anti-MDA5 antibodies signify clinically amyopathic DM (CADM) with severe ILD, linked to dysregulated neutrophil extracellular trap (NET) formation. In immune-mediated necrotizing myopathies (IMNMs), anti-SRP and anti-HMGCR antibodies induce complement-mediated myopathy, typically following statin exposure. Additionally, anti-TRIM72 antibodies emerge as potential diagnostic markers in IIMs. Anti-cN1A autoantibodies are linked to inclusion body myositis (IBM) and play a decisive role in muscle protein degradation. Meanwhile, anti-FHL1 autoantibodies are associated with severe disease manifestations and muscle damage, as established in experimental models. Anti-eIF3 autoantibodies, recently identified in polymyositis (PM) patients, are rarely detected (<1%) and associated with a favorable prognosis. Elucidating these autoantibodies is anticipated to not only assist in early diagnosis and disease stratification but also inform targeted therapeutic interventions, emphasizing the intricate interplay between autoimmunity, cellular dysfunction, and clinical outcomes in IIMs.

Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

Statin-Induced Autoimmune Myopathy: A Diagnostic Challenge in Muscle Weakness.

BACKGROUND Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. Muscle-related adverse effects of statins have been very challenging in clinical practice and they necessitate high clinical suspicion. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. CASE REPORT We present a 69-year-old man with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months, with a creatinine kinase of 8323 U/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, he did not show significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A reductase antibody was ordered and he was started on IV steroids. Anti-HMG Co-A reductase antibody was positive, and the rest of myopathy workup was negative. Meanwhile, the patient's muscle weakness significantly improved with IV steroid. He was discharged on methylprednisolone with close outpatient rheumatology follow-up. CONCLUSIONS Muscle-related adverse effects of statins, including rhabdomyolysis and myopathy, can fail to respond to conservative management. It is crucial to identify and manage statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness and elevated CK while on statin therapy who do not respond to intravenous fluid alone.

Lactobacillus delbrueckii alleviates lipopolysaccharide-induced muscle inflammation and atrophy in weaned piglets associated with inhibition of endoplasmic reticulum stress and protein degradation.

Pro-inflammatory cytokines in muscle play a pivotal role in physiological responses and in the pathophysiology of inflammatory disease and muscle atrophy. Lactobacillus delbrueckii (LD), as a kind of probiotics, has inhibitory effects on pro-inflammatory cytokines associated with various inflammatory diseases. This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)-induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc × Landrace × Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS-challenged (LPS); (3) 0.2% LD diet and LPS-challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4 h after LPS or saline injection, the blood and muscle samples were collected for further analysis. Our results showed that dietary supplementation of LD significantly attenuated LPS-induced production of pro-inflammatory cytokines IL-6 and TNF-α in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the muscle, which correlated with the anti-inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS-induced muscle atrophy, indicated by a higher expression of muscle atrophy F-box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy-related protein 5 (ATG5) at the transcriptional level, whereas pretreatment with LD led to inhibition of these upregulations, particularly genes for MuRF1 and ATG5. Moreover, LPS-induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2α (eIF-2α) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1α and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti-inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro-inflammatory cytokines through the inactivation of the ER stress/NF-κB singling pathway, along with the reduction in protein degradation.

Incidence and prevalence of idiopathic inflammatory myopathies in Thailand from the Ministry of Public Health data analysis.

The epidemiology of idiopathic inflammatory myopathies (IIMs) varies by country. Investigating the epidemiological profile among Thai IIMs could help to inform public health policy, potentially leading to cost-reducing strategies. We aimed to assess the prevalence and incidence of IIM in the Thai population between 2017 and 2020. A descriptive epidemiological study was conducted on patients 18 or older, using data from the Information and Communication Technology Center, Ministry of Public Health, with a primary diagnosis of dermatopolymyositis, as indicated by the ICD-10 codes M33. The prevalence and incidence of IIMs were analyzed with their 95% confidence intervals (CIs) and then categorized by sex and region. In 2017, the IIM cases numbered 9,074 among 65,204,797 Thais, resulting in a prevalence of 13.9 per 100,000 population (95% CI 13.6-14.2). IIMs were slightly more prevalent among women than men (16.8 vs 10.9 per 100,000). Between 2018 and 2020, the incidence of IIMs slightly declined from 5.09 (95% CI 4.92-5.27) in 2017 and 4.92 (95% CI 4.76-5.10) in 2019 to 4.43 (95% CI 4.27-4.60) per 100,000 person-years in 2020. The peak age group was 50-69 years. Between 2018 and 2020, the majority of cases occurred in southern Thailand, with incidence rates of 7.60, 8.34, and 8.74 per 100,000 person-years. IIMs are uncommon among Thais, with a peak incidence in individuals between 60 and 69, especially in southern Thailand. The incidence of IIMs decreased between 2019 and 2020, most likely due to the COVID-19 pandemic, which reduced reports and investigations.

Protracted Febrile Myalgia Syndrome: A Rare and Difficult Manifestation of Familial Mediterranean Fever.

OBJECTIVE: Protracted febrile myalgia syndrome (PFMS) is characterized by severe myalgia, fever, abdominal pain, and arthralgia/arthritis episodes lasting for several weeks in patients with familial Mediterranean fever. Treatment options include nonsteroidal anti-inflammatory drugs, corticosteroids, and anti-interleukin-1 therapy. This study aimed to share our experiences of PFMS so as to shed light on this rare and elusive condition. METHODS: This cross-sectional analysis included 17 patients diagnosed with PFMS at our pediatric rheumatology clinic between January 2018 and September 2023. RESULTS: In our clinic, 17 (1%) of 1663 familial Mediterranean fever patients presented with PFMS, and it was the initial manifestation in 10 patients (58.8%) in the cohort. Eight of the 17 patients had an M694V homozygous mutation in the MEFV gene. A magnetic resonance imaging showed myositis and fasciitis in just 1 patient, and myositis alone was evident in 5 others. Symptoms improved in 2 patients with nonsteroidal anti-inflammatory drugs, whereas prednisolone improved symptoms in 12 patients and anakinra was required in 3 patients. Patients who received anakinra had another severe attack and required long-term anakinra or canakinumab. CONCLUSIONS: Syndrome for PFMS is difficult to recognize as it can sometimes be the first manifestation of familial Mediterranean fever. The syndrome is not accompanied by fever in some patients, even though the word febrile is part of its name. Most patients respond dramatically to nonsteroidal anti-inflammatory drugs or corticosteroids. In some patients with PFMS, long-term anakinra or canakinumab treatment may be more useful in preventing severe attacks of PFMS than short-term (5 to 7 days) anakinra treatment.

Autoantibodies and damage in patients with idiopathic inflammatory myopathies: A longitudinal multicenter study from the MYONET international network.

OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

High-intensity resistance training improves quality of life, muscle endurance and strength in patients with myositis: a randomised controlled trial.

Myositis is associated with reduced quality of life, which is accompanied by significant impairments in muscle endurance and strength, altogether representing cardinal traits in patients with myositis. This randomised controlled trial aimed to investigate the effect of high-intensity resistance training on quality of life in patients with myositis. Thirty-two patients with established, stable myositis were randomised to 16 weeks of high-intensity resistance training (intervention group) or 16 weeks of usual care (control group). Primary outcome was quality of life assessed as the change in the physical component summary score (PCS) of the Short Form-36 health questionnaire from baseline to post-intervention. Secondary outcomes included functional capacity measures, such as functional index 3, and International Myositis Assessment and Clinical Studies Group (IMACS) disease activity and damage core set measures, including manual muscle testing 8 (MMT8). The primary outcome PCS showed an improvement in favour of high-intensity resistance training with a between-group difference of 5.33 (95% CI 0.61; 10.05) (p = 0.03). Additionally, functional index 3 showed a between-group difference indicating greater gains with high-intensity resistance training 11.49 (95% CI 3.37; 19.60) (p = 0.04), along with a between-group improvement in MMT8 1.30 (95% CI 0.09; 2.51) (p = 0.04). High-intensity resistance training for 16 weeks effectively improved quality of life in patients with myositis. Clinical measures of muscle endurance and muscle strength were also found to improve with high-intensity resistance training, while patients stayed in disease remission. Consequently, progressively adjusted high-intensity resistance training is feasible and causes no aggravation of the disease, while benefitting patients with myositis.Clinical trial registration: Clinicaltrials.gov ID: NCT04486261- https://clinicaltrials.gov/study/NCT04486261 .

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group.

BACKGROUND: Validated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. METHODS: Adults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. RESULTS: 135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. CONCLUSIONS: PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.

Differences in the autoantibody phenotypes and long-term outcomes between juvenile- and adult-idiopathic inflammatory myopathies.

OBJECTIVE: To investigate differences in autoantibodies, clinical features, and long-term outcomes between juvenile-idiopathic inflammatory myopathy (IIM) and adult-IIM METHODS: Autoantibodies, clinical characteristics, and drug-free conditions for a maximum of 20 years were retrospectively analyzed in 320 Japanese IIM patients (juvenile-IIM, n = 34; adult-IIM, n = 286) using the Kyoto University Registry. RESULTS: Autoantibodies observed in juvenile-IIM were anti-TIF1-γ (15 %), anti-MDA-5 (15 %), anti-ARS (9 %), and anti-NXP-2 (6 %). Those observed in adult-IIM were anti-ARS (32 %), anti-MDA-5 (23 %), anti-TIF1-γ (8 %), anti-SRP (8 %), anti-Mi-2 (2 %), and anti-NXP-2 (1 %). The cumulative drug-free condition rate was higher in juvenile-IIM than in adult-IIM up to 20 years (juvenile-IIM vs. adult-IIM, 34 % vs. 18 %, p = 0.0016). Anti-TIF1-γ was associated with lesser muscle symptoms (60 % vs. 90 %), malignancy (0 % vs. 57 %), and glucocorticoid use (40 % vs. 86 %) in juvenile-IIM compared to adult-IIM, while juvenile-IIM more achieved drug-free conditions (60 % vs. 25 %). Both juvenile-IIM and adult-IIM with anti-MDA-5 demonstrated a high frequency of amyopathic dermatomyositis, interstitial lung disease (ILD), and multi-immunosuppressive therapy, with high drug-free conditions (50 % vs. 49 %). Both juvenile-IIM and adult-IIM with anti-ARS showed frequent skin rashes, muscle symptoms, and ILD, frequent need for multi-immunosuppressive therapy, and low drug-free condition rates (0 % vs. 3 %). Both juvenile-IIM and adult-IIM with anti-NXP-2 showed frequent skin rashes and muscle symptoms, low ILD frequency, and frequent use of methotrexate and glucocorticoids, which did not achieve drug-free conditions (0 % vs. 0 %). CONCLUSIONS: Drug-free condition was achieved more frequently in juvenile-IIM patients than adult-IIM patients. Specific autoantibodies were associated with different clinical characteristics and outcomes between juvenile-IIM and adult-IIM.

Clinical characteristics of idiopathic inflammatory myopathies patients with anti-PM/Scl antibodies.

OBJECTIVES: To analyze the clinical features of idiopathic inflammatory myopathies (IIMs) patients with anti-PM/Scl antibodies. METHODS: In this retrospective cohort study, we compared the clinical manifestations between patients who were solely positive for anti-PM/Scl antibodies (isolated anti-PM/Scl group) and those with a coexistence of anti-PM/Scl antibodies and myositis-specific antibodies (MSAs) (double-positive group). RESULTS: Sixty-five IIMs patients positive for anti-PM/Scl antibodies were included, among whom 51 (78.5 %) were females, with a mean age of 49.1 years. Thirty-four (52.3 %) patients coexisted with MSAs. Compared to the double-positive group, the isolated anti-PM/Scl group demonstrated a higher proportion of women (90.3 % vs 67.6 %, p = 0.026) and a higher incidence of sclerodactyly (16.1 % vs 0, p = 0.021). Although there were no differences in the incidence of muscular weakness, dysphagia, or creatine kinase levels, thigh magnetic resonance imaging (MRI) revealed less muscle edema, atrophy, and fatty replacement in the isolated anti-PM/Scl group (p < 0.05). Interstitial lung disease (ILD) occurred in 80 % of patients, more frequently in the double-positive group (90.6 % vs 67.9 %, p = 0.028). According to HRCT, non-specific interstitial pneumonia (NSIP) was the most common pattern among anti-PM/Scl antibodies positive IIMs patients. The double-positive group exhibited higher ferritin levels, and a lower peripheral lymphocyte count (p < 0.05). The mortality rate in the double-positive group was higher than that in the isolated anti-PM/Scl group (20.6 % vs 0, p = 0.034). CONCLUSION: Among IIMs patients who tested positive for anti-PM/Scl antibodies, ILD emerged as the predominant clinical feature, particularly when combined with MSA. Notably, patients with isolated anti-PM/Scl antibodies exhibited a favorable prognosis following immunotherapy.

Absence of Pathogenic Mutations and Strong Association With HLA-DRB1*11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy.

BACKGROUND AND OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype. METHODS: Clinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed. RESULTS: Patients, aged 3-25 years and mostly female (90.9%), presented with subacute proximal weakness progressing over many years and high CK levels (>1,000 U/L). Diagnostic delay ranged from 3 to 27 years. WES did not reveal any pathogenic variants. HLA-DRB1*11:01 carrier frequency was 60%, a significantly higher proportion than in the control population. No upregulation or mislocalization of the enzyme in statin-exposed or statin-naïve anti-HMGCR+ patients was observed, compared with controls. DISCUSSION: WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.

Association of anti-Ro-52 antibodies with occurrence of interstitial lung disease in patients with idiopathic inflammatory myopathy.

BACKGROUND: Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. METHODS: This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth's logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. RESULTS: This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. CONCLUSIONS: Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.