Inflammatory Myopathies Research Articles

Methotrexate: Use in the Post Dobbs v. Jackson Era.

Methotrexate is one of the most frequently used medications for the treatment of rheumatic diseases. Although initially developed for use as chemotherapy for both solid and hematologic malignancies, it was used as early as the 1960s with success for rheumatoid arthritis (RA) and psoriatic arthritis, ultimately being approved by the US Food and Drug Administration for the treatment of RA in 1988. Beyond RA and psoriatic arthritis, methotrexate is used in the treatment of systemic lupus erythematosus, idiopathic inflammatory myopathies, and other inflammatory conditions. Methotrexate is cytotoxic to the trophoblast and has been used to treat both ectopic pregnancy and gestational trophoblastic neoplasia, leading to studies in the early 1990s that showed it was effective and safe for early abortion in combination with prostaglandin E1 analog misoprostol. Methotrexate is also a teratogen, causing serious birth defects in 6%-10% of patients taking it while pregnant. Additionally, women are more likely to be affected by both RA at SLE, as compared with males, thus worsening the burden of these adverse effects. Both methotrexate's history of use as an abortifacient and its teratogenic properties make its use more complicated in the current era of abortion policy in the United States following the Dobbs v. Jackson Women's Health Organization ruling. Recently published data suggest that this ruling has affected both provider perspectives and patient experiences as it relates to methotrexate use. In the post-Dobbs era, the role of the rheumatologist as it relates to patients' sexual and reproductive health is likely to expand.

553P Brachio-cervical inflammatory myopathy, an unknown disease with diverse serological and histopathological findings and poor response to treatment

553P Brachio-cervical inflammatory myopathy, an unknown disease with diverse serological and histopathological findings and poor response to treatment

Incidence and outcomes for children with idiopathic inflammatory myopathy in Western Australia-a long-term population-based study.

To determine the incidence and health outcomes for juvenile idiopathic inflammatory myopathy (JIIM) in a long-term whole-population study. We included patients under 18 years hospitalized in Western Australia (WA) from 1985 and 2015 with incident JIIM as defined by pertinent diagnostic codes for dermatomyositis (JDM) polymyositis (JPM), other JIIM and overlap myositis (JOM). We compared clinical outcomes and modified Charlson comorbidity scores with age and gender matched (2:1 ratio) patients with new onset juvenile idiopathic arthritis (JIA). Trends over time for annual incidence rate per million child-population (AIR) were analyzed by least square regression and survival by Kaplan-Meier curves. We included 40 patients with JIIM (63% female, median age 8.5 years) for an average AIR of 2.52 per million (CI 1.09-5.57). AIR was stable over time leading to a point prevalence of 52.61 (CI 40.57-67.06) in 2015. Most patients (80%) were classified as JDM with an AIR for JDM of 2.02 (CI 1.09-5.58) and AIR for the combined other JIIM at 0.51 (CI 0.24-1.15). There was female preponderance (62.5%) in both JIIM groups, but no evidence of seasonality. Over a median follow-up of 13 years, one- and ten-year survival was 94.1%. Compared to JIA patients, readmission (80.4 vs. 63.7, p = .02) and infection rates (15.2 vs. 9.6, p < .01) per 100 person-years were higher for JIIM, with similar frequency of interstitial lung disease, fractures, and thrombotic events. At last observation, nearly all patients in both JIIM cohorts (97.5 vs. 92.5%) had accrued some form of comorbidity. The overall incidence of JIIM leading to hospitalization in WA was stable over 30 years. JIIM prognosis remains suboptimal due to early mortality and accrual of long-term comorbidity.

562P Rare mimics of idiopathic inflammatory myopathies – a single centre cohort from India

562P Rare mimics of idiopathic inflammatory myopathies – a single centre cohort from India

556P Contractile properties of permeabilised single muscle fibres from female patients with idiopathic inflammatory myopathies

556P Contractile properties of permeabilised single muscle fibres from female patients with idiopathic inflammatory myopathies

552P Binding immunoglobulin protein (BiP) abundance and distribution in idiopathic inflammatory myopathies (IIM)

552P Binding immunoglobulin protein (BiP) abundance and distribution in idiopathic inflammatory myopathies (IIM)

576P High precision quantification of ICAM-1 highlights similarities and differences between subgroups of Idiopathic inflammatory myopathies

576P High precision quantification of ICAM-1 highlights similarities and differences between subgroups of Idiopathic inflammatory myopathies

Accurate Visualization of C4d Complement Fragment in Immunohistochemistry by C-Terminal Linear Neoepitope-Specific Antibodies

C4d is the end degradation product of activated complement component C4b that appears during the early steps of the classical and lectin complement pathways. Within the primary sequence of C4d, there is a reactive thioester group that binds covalently to nearby surfaces, thus labeling the locations of complement activation. This feature makes C4d a target for immunohistochemical staining aimed to aid the diagnosis of, among others, the antibody-mediated rejection of transplanted organs, membranous glomerulonephritis, bullous pemphigoid, or inflammatory myopathies. However, the credibility of C4d immunostaining is debatable, as a high background in surrounding tissues and body fluids and diffused patterns of deposits in target structures are experienced with some of the available anti-C4d antibodies. Herein, we present an improved version of a rabbit anti-C4d antibody, originally raised against the C-terminal linear neoepitope of this complement fragment. Minor cross-reactivity with C4b and native C4 proteins, measured by ELISAs, as well as relatively low concentrations necessary for obtaining a specific signal in immunohistochemical analyses of formalin-fixed paraffin-embedded material, makes the improved antibody superior to commercially available rabbit monoclonal anti-C4d antibody SP91 dedicated to ex vivo diagnostics, as demonstrated by the staining of a panel of kidney transplant biopsies.

Comparison of Lineblot and Immunoprecipitation Methods in the Detection of Myositis-Specific and Myositis-Associated Antibodies in Patients with Idiopathic Inflammatory Myopathies: Consistency with Clinical Diagnoses.

Background: the reference method for detection of myositis-specific and myositis-associated antibodies (MSAs and MAAs) is considered immunoprecipitation (IP), but it is routinely replaced by semi-automated methods, like lineblot (LB). Few data are available on the consistency with clinical diagnoses; thus, we aim at analysing these aspects. Methods: sixty-nine patients with idiopathic inflammatory myopathies (IIM) were studied via LB (Myositis Antigens Profile 3 EUROLINE, Euroimmun) and IP (RNA and protein antigens). The degree of concordance between methods was calculated using Cohen's coefficient. Results: a substantial concordance was found for anti-Ku and anti-PM/Scl and a moderate concordance was found for anti-Jo1 and anti-Mi-2, while a fair concordance was found for anti-EJ, anti-SRP, and anti-Ro52 antibodies. The concordance could not be calculated for anti-OJ, anti-PL-7, anti-PL-12, anti-NXP2, anti-TIF1ɣ, and anti-MDA5, because they were only detected with one method. Multiple MSAs were found only with LB in 2/69 sera. Anti-MDA5, TIF1ɣ, NXP2 (detected via IP), and anti-Jo1 in anti-synthetase syndrome (both LB and IP) had the best concordance with clinical diagnosis. Conclusions: LB and IP show substantial concordance for PM/Scl and Ku, and moderate concordance for Jo1 and Mi-2, with a good concordance with clinical diagnoses. IP shows a high performance for DM-associated MSAs. LB seems to be more sensitive in detecting anti-Ro52 antibodies, but it identified multiple MSAs, unlike IP.

The impact of multimorbidity on QoL in inflammatory myopathies: COVAD cluster analysis.

The presence of comorbidities can substantially affect patients' quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs), and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined Basic Multimorbidity (BM) as the presence of ≥ 2 non-rheumatic chronic conditions and Complex Multimorbidity (CM) as the presence of ≥ 3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical Clustering on Principal Components was performed for grouping. Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs, and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (OR: 1.62 vs oAIRDs and 2.95 vs HCs, p< 0.01), BM (OR 1.66 vs oAIRDs and 3.52 vs HCs, p< 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, p< 0.01), and mental health disorders (MHDs) (OR 1.33 vs oAIRDs and 2.63 vs HCs, p< 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all p< 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM, and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

Volumetric muscle composition analysis in sporadic inclusion body myositis using fat-referenced magnetic resonance imaging: Disease pattern, repeatability, and natural progression.

Fat-referenced magnetic resonance imaging (MRI) has emerged as a promising volumetric technique for measuring muscular volume and fat in neuromuscular disorders, but the experience in inflammatory myopathies remains limited. Therefore, this work aimed at describing how sporadic inclusion body myositis (sIBM) manifests on standardized volumetric fat-referenced MRI muscle measurements, including within-scanner repeatability, natural progression rate, and relationship to clinical parameters. Ten sIBM patients underwent whole-leg Dixon MRI at baseline (test-retest) and after 12 months. The lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) of the quadriceps, hamstrings, adductors, medial gastrocnemius, and tibialis anterior were computed. Clinical assessments of IBM Functional Rating Scale (IBMFRS) and knee extension strength were also performed. The baseline test-retest MRI measurements were used to estimate the within-subject standard deviation (sw). 12-month changes were derived for all parameters. The MRI measurements showed high repeatability in all muscles; sw ranged from 2.7 to 18.0 mL for LMV, 0.7-1.3 percentage points (pp) for MFF, and 0.2-0.7 pp for MFI. Over 12 months, average LMV decreased by 7.4% while MFF and MFI increased by 3.8 pp and 1.8 pp, respectively. Mean IBMFRS decreased by 2.4 and mean knee extension strength decreased by 32.8 N. The MRI measurements showed high repeatability and 12-month changes consistent with muscle atrophy and fat replacement as well as a decrease in both muscle strength and IBMFRS. Our findings suggest that fat-referenced MRI measurements are suitable for assessing disease progression and treatment response in inflammatory myopathies.

Genetic association between TNFA polymorphism rs1799964 with a more severe course of idiopathic inflammatory myopathies

Genetic association between TNFA polymorphism rs1799964 with a more severe course of idiopathic inflammatory myopathies

Peripheral neuroimmunological diseases - Neuropathological insights and clinical perspectives

This article deals with peripheral neuroimmunological diseases and briefly outlines the currently most important aspects and treatment developments. Idiopathic inflammatory myopathies have different mechanisms of development, manifestations and prognoses. New classification systems and more specific treatment concepts have been developed. The IIMs include different subgroups. These entities can have specific autoantibodies. Diagnostically, amuscle biopsy is generally desirable for aprecise diagnosis and is essential in unclear cases. Primary systemic vasculitides can be divided into different groups based on the predominant pattern of involvement, while secondary vasculitides and single organ vasculitides are also differentiated. Vasculitic myopathy cannot be equated with myositis and areliable distinction is currently only possible by a muscle biopsy. Treatment concepts should be developed on an interdisciplinary basis. Chronic inflammatory demyelinating polyneuropathy is the most frequent immune-mediated neuropathy and is characterized by apredominant demyelination of the motor and sensory nerves. The disease course runs in phases or is progressive and leads to significant disability and reduction in quality of life, despite current standard treatment. Novel treatment approaches are currently undergoing clinical trials. Myasthenia gravis, with the leading symptom of exercise-induced muscle weakness, is caused by autoantibodies against structures of the neuromuscular endplate. Autoantibody testing is the most important pillar in the diagnosis and is now also increasingly guiding treatment decisions. Overall, peripheral neuroimmunological diseases represent aheterogeneous group. Increasing knowledge of the pathophysiology is the key to numerous developments in diagnostics and treatment, which could lead to far-reaching practical changes in the future.

The expression of genes involved in the response of airway epithelial cells to simulated viral infection in patients with idiopathic inflammatory myopathies

The expression of genes involved in the response of airway epithelial cells to simulated viral infection in patients with idiopathic inflammatory myopathies

Shift in landscape of idiopathic inflammatory myopathies from before the COVID-19 pandemic and post-pandemic period – growing incidence of immune-mediated necrotizing myopathy

Shift in landscape of idiopathic inflammatory myopathies from before the COVID-19 pandemic and post-pandemic period – growing incidence of immune-mediated necrotizing myopathy

Cardiac involvement in idiopathic inflammatory myopathies

Cardiac involvement in idiopathic inflammatory myopathies

Nailfold Capillaroscopy Changes in Patients with Idiopathic Inflammatory Myopathies.

Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders characterized by progressive proximal muscle weakness and varying extra-muscular manifestations. The latest 2017 EULAR/ACR criteria classify them into subgroups. This study aims to evaluate the role of nailfold capillaroscopy (NFC) as a diagnostic and prognostic tool in IIMs by comparing capillaroscopic patterns across different IIM subtypes. Methods: We conducted an observational, cross-sectional study at the Institute of Rheumatology in Belgrade, analyzing 90 patients diagnosed with IIMs per the 2017 EULAR/ACR criteria. Patients were categorized into dermatomyositis (DM) (n = 37), polymyositis (PM) (n = 35), amyopathic dermatomyositis (ADM) (n = 13), and juvenile dermatomyositis (JDM) (n = 5). A control group of 35 patients with primary Raynaud's phenomenon was also included. NFC findings, clinical manifestations, and laboratory data were compared across the groups. Results: In DM, 81.9% exhibited a scleroderma capillaroscopic pattern, which was also present in 76.9% of ADM patients. In PM, the most common pattern was nonspecific changes (48.6%). JDM patients showed a high prevalence of scleroderma changes (n = 4 (80%)). Scleroderma patterns correlated with Gottron's papules, heliotrope rash, periungual erythema, Raynaud's phenomenon, and interstitial lung disease (ILD). No significant differences were found in laboratory parameters across capillaroscopic groups, except for a higher prevalence of anti-Jo1 antibodies in patients with nonspecific capillaroscopic changes. Conclusions: NFC is a valuable tool for differentiating IIM subtypes and correlating clinical manifestations with specific capillaroscopic patterns. The high prevalence of scleroderma changes in DM and ADM suggests their potential as a diagnostic and prognostic marker in IIMs. Further research with larger cohorts is warranted to validate these findings.

Can we differentiate patients with dysferlinopathies and inflammatory myopathies by ultrasound? A discriminant analysis study.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that are characterized by inflammation and muscle weakness. Dysferlinopathies are autosomal recessive limb-girdle muscular dystrophies caused by mutations in DYSF, which share a similar clinical presentation and histopathological inflammatory changes. To determine the sonographic differences between dysferlinopathies and IIM and whether these differences allow their classification. This observational, cross-sectional, and analytical study evaluated 20 muscles from 11 patients with dysferlinopathies and 11 patients with IIM. The patients were matched for age, sex, and disease duration. Clinical and laboratory variables were analyzed. Semi-quantitative scales were used to weigh the gray scale and power Doppler muscle abnormalities. Descriptive statistics were computed and discriminant analysis was performed to determine the ultrasound variables that best predicted the final diagnosis. Forty muscles were evaluated. Atrophy and higher Heckmatt scale scores were observed in patients with dysferlinopathies. A set of three muscles (biceps/brachialis, quadriceps, and gastrocnemius) had a diagnostic accuracy of 100% (sensitivity, 100%; specificity, 100%; canonical coefficient, 0.733 p < 0.001). A set of two formulas was used to classify both diseases correctly. In the present study, scanning of three muscle groups showed high diagnostic accuracy in differentiating dysferlinopathies from MII. Ultrasound can be used as an initial test in patients with suspected muscle disease or as an additional tool to support diagnosis in controversial cases.

Inclusion body myositis coexisting with severe aortic stenosis due to bicuspid aortic valve: A case report and literature review of cardiac involvement in inclusion body myositis

AbstractInclusion body myositis (IBM) is an idiopathic inflammatory myopathy, but cardiac involvement has rarely been reported. Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, the relationship between IBM and valvular heart disease remains unknown. We herein report the first case of a 68‐year‐old male patient with IBM coexisting with severe aortic stenosis due to BAV that was successfully treated with aortic valve replacement. To date, only 10 cases of IBM with cardiac manifestation, including our case, have been reported, and we review the current literature on cardiac involvement in patients with IBM.

Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis.

Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM). An ecto-5'-nucleotidase (CD73) inhibitor, adenosine receptor agonists, a hypoxia-inducible factor-1α (HIF-1α) inhibitor or a vehicle were administered to control and EAM mice. Murine splenic CD4+ or regulatory T cells (Tregs) were isolated using magnetic beads and subsequently stimulated with an adenosine A2B receptor agonist, a HIF-1α inhibitor, or vehicle in vitro. In cross-sectional studies, we collected 64 serum samples (69% female, 49±9years), 63 peripheral blood samples (70% female, 50±11years), and 34 skeletal muscle samples (71% female, 63±6years) from patients with IIM. Additionally, 35 serum samples and 30 peripheral blood samples were obtained from age- and sex-matched healthy controls, and six quadriceps muscle samples were collected from patients with osteoarthritis to serve as the normal group. Patients with IIM exhibited increased CD73 [dermatomyositis (DM), polymyositis (PM): P<0.01; immune-mediated necrotizing myopathy (IMNM): P<0.0001] and adenosine deaminase (ADA) expression (DM: P<0.001; PM, IMNM: P<0.0001) in the skeletal muscles, and serum ADA levels [56.7 (95% CI: 53.7, 58.7) vs. 198.8 (95% CI: 186.2, 237.3) ng/μL, P<0.0001]. Intervention with a CD73 inhibitor exacerbated (P=0.0461), whereas adenosine receptor agonists (A1: P=0.0009; A2B: P<0.0001; A3: P=0.0001) and the HIF-1α inhibitor (P=0.0044) alleviated skeletal muscle injury in EAM mice. Elevated expression of programmed cell death protein-1 (PD1: P=0.0023) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3: P<0.0001) in skeletal muscles of patients with IIM were correlated with creatine kinase levels (PD1, r=0.7072, P<0.0001; TIM3, r=0.4808, P=0.0046). PD1+CD4+ (r=0.3243, P=0.0115) and PD1+CD8+ (r=0.3959, P=0.0017) T cells were correlated with Myositis Disease Activity Assessment Visual Analogue Scale scores (muscle) in IIM. The exhausted Tregs were identified in the skeletal muscles of patients with IIM. Activation of the A2B adenosine receptor downregulated HIF-1α (protein or mRNA level, P<0.01), resulting in decreased T helper cell 17 (Th17) (13.58% vs. 5.43%, P=0.0201) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3)+ Th17 (16.32% vs. 6.73%, P=0.0029), decreased exhausted Tregs (PD1+ Tregs: 53.55% vs. 40.28%, P=0.0005; TIM3+ Tregs: 3.93% vs. 3.11%, P=0.0029), and increased Tregs (0.45% vs. 2.89%, P=0.0006) in EAM mice. The exhausted T cells may be pathogenic in IIM,andthe activation of adenosine A2B receptor signalling pathway can regulate Th17/Treg balance and inhibit Tregsexhaustion, thereby slowing EAM disease progression.