OBJECTIVES: Discordance between patient and physician perspectives on disease activity in idiopathic inflammatory myopathies (IIM) can compromise treatment outcomes. This study aimed to characterize patterns of discordance and distinct longitudinal trajectories in the MyoCite IIM cohort. METHODS: Discordance was defined as a difference between patient (PtGA) and physician (PhGA) global assessments (0-10cm scale) of ≥ ±1cm. Prevalence was assessed at baseline (n = 244) and longitudinally at 6, 12, and 24 months (n = 128). Linear mixed-effects (n = 191) and bidirectional mediation models identified independent drivers and causal pathways. RESULTS: Clinically significant baseline discordance occurred in 19.3% of patients, predominantly manifesting as positive discordance (PtGA>PhGA; 16.8%) across IIM subtypes (dermatomyositis, polymyositis, overlap myositis, anti-synthetase syndrome). Over 24 months, discordance narrowed with treatment. Baseline positive discordance strongly predicted poorer functional capacity (HAQ) at 1 year (p= 0.034). While objective muscle weakness statistically drove the gap (MMT-8: β = -0.013, 95% CI - 0.022 to - 0.004; standardised β = -0.155, p= 0.006), fluctuations had minimal absolute impact. A distinct subset (25%) maintained persistent discordance, exhibiting high subjective pain despite normalized muscle enzymes. Bidirectional mediation analysis revealed discordance unidirectionally drives future functional disability through unmanaged pain (32.1% mediated, p< 0.001) while reverse mediation (HAQ driving discordance via pain) was not statistically significant. CONCLUSION: Patient-physician discordance in IIM is an active, upstream driver of future functional loss, mediated significantly by pain, rather than a mere reflection of existing objective damage. It serves as a critical marker requiring early targeted pain intervention and integration of patient-reported outcomes into routine clinical monitoring.
Immunoglobulin G4-related disease (IgG4-RD) is a rare, multisystemic fibro-inflammatory condition affecting various organs, including kidneys, lungs, nasal cavity, pancreas, salivary glands, and orbit. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) is a multi-systemic inflammatory vascular disease encompassing eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA). It often overlaps with the organs or tissues affected by IgG4-RD. Clinically, some individuals with IgG4-RD are ANCA-positive, while some with AAV exhibit elevated IgG4 levels or IgG4-positive plasma cell infiltration, making these conditions difficult to distinguish. Reports have documented cases of overlap syndromes involving IgG4-RD and AAV, highlighting shared pathogenic mechanisms that may include macrophages, B cells, CD4+T cells, and inflammatory cytokines. However, the pathophysiological mechanism underlying these overlap syndromes remains unclear. This review examines potential pathophysiological links between IgG4-RD and AAVs (GPA/MPA) overlap syndromes.
Data on interstitial lung disease (ILD) in Indian patients with idiopathic inflammatory myopathy (IIM) is limited. We aimed to determine the characteristics of ILD, and factors associated with the progression of ILD in Indian patients with IIM. A prospective single centre cohort of 86 consecutive adult-onset IIM patients recruited between October 2020 and December 2025 were studied. The diagnosis of IIM related ILD (IIM-ILD) was made after high resolution CT Thorax. Progression of ILD was defined as per the 2022 ATS/ERS/JRS/ALAT guidelines for progressive pulmonary fibrosis (PPF). Multivariate logistic regression was done to identify independent factors associated IIM-ILD. Comparisons were made between patients with PPF and those without PPF. Of the 86 IIM patients, ILD was seen in 59.3% of patients (n = 51). The most common radiological patterns were non-specific interstitial pneumonia (58.8%), organizing pneumonia (21.6%), usual interstitial pneumonia (13.7%), and overlap of NSIP-OP (5.9%). The most common subsets were anti synthetase syndrome (66.6%, 34/51), dermatomyositis (23.5%, 12/51) and overlap myositis (7.8%, 4/51). The most common myositis specific autoantibody was anti-Jo1 (27.4%, 14/51) and the most common myositis associated autoantibody was anti-Ro52 (58.8%, 30/51). On multivariate logistic regression, heliotrope rash (OR 0.25, 95% CI 0.06-0.96, p = 0.04), arthritis (OR 3.57, 95% CI 1.15-11.07, p = 0.03) and anti-Ro52 (OR 4.37, 95% CI 1.40-13.40, p = 0.01) were associated with ILD. Of the 37 patients with IIM-ILD evaluated for progression, 18.9% (n = 7) developed PPF within 1 year of follow up. Amyopathic presentation and NSIP/OP pattern were associated with PPF (p = 0.02, p = 0.03 respectively). The frequency of ILD is high in Indian patients with IIM (59.3%, 51/86) and of the IIM-ILD evaluated for progression, around one fifth developed PPF (18.9%, 7/37). A baseline screening for ILD is mandatory in IIM
This study aimed to investigate the relationship between specific autoantibodies, particularly anti-Ro52, and the development of interstitial lung disease (ILD) in patients with autoimmune diseases (AID), with the goal of identifying potential biomarkers for the early detection and management of ILD. A retrospective cohort study was conducted at Peking Union Medical College Hospital, involving 2,021 AID patients who underwent antinuclear antibody (ANA) testing between 2017 and 2019. Clinical and serological data were collected to assess the presence of ILD and its association with specific autoantibodies. Least absolute shrinkage and selection operator (LASSO) regression was used to identify predictors of ILD. Among the 2,021 patients, ILD prevalence varied across AID subgroups, with the highest rates observed in idiopathic inflammatory myopathies (IIM), overlap syndrome, and systemic sclerosis. Anti-Ro52 was significantly more frequent in IIM patients with ILD compared to those without ILD (83.0% vs. 37.8%, p<0.0001). Anti-RNP was detected at a significantly higher rate in lupus-ILD patients. Additionally, positivity rates of anti-SSA/Ro60 and anti-CENP B were inversely associated with ILD in Sjögren's disease and systemic sclerosis, respectively. LASSO regression analysis identified anti-Ro52, age, and anti-MDA5 as significant predictors of ILD development in IIM. Anti-Ro52 positivity was associated with a more than two-fold increased risk of ILD progression in mixed connective tissue disease. Anti-Ro52, together with age and anti-MDA5, was identified as a significant predictor of ILD in IIM patients. This study highlights the potential of autoantibodies as biomarkers for early detection and management of ILD in AID patients.
Antitopoisomerase I (ATA), anticentromere (ACA) and anti-RNA polymerase III (RNAP3) antibodies are included in the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis (SSc). A subset of patients with SSc satisfy criteria but may lack these specific autoantibodies, being classified as 'triple-negative'. We conducted a retrospective evaluation of triple-negative patients with SSc prevalence and clinical features among the multicentric Systemic sclerosis Progression INvestiGation registry. Out of 1480 patients with SSc, 295 (19.9%) were triple-negative, while 1185 (81.1%) had SSc-specific antibodies: ACA (54.3%), ATA (43.6%) and RNAP3 (2.1%). The triple-negative group showed a higher prevalence of myopathy (16.7% vs 10.1%, p=0.003), suggested by higher creatine phosphokinase (CPK) levels (126.2 vs 92.5 U/mL, p=0.002), more frequent CPK increase over 2-3 times (2.4% vs 0.2%, p=0.028). Triple-negative patients also exhibited fewer vascular complications, including digital ulcers (17.3% vs 22.8%, p=0.04) and calcinosis (8.2% vs 12.8%, p=0.027), and a higher prevalence of interstitial lung disease (p<0.001). Consistently, lower diffusing capacity for carbon monoxide (66.4% vs 70.98%, p=0.004) and forced vital capacity (97.01% vs 102.92%, p<0.001) were found in the triple-negative group. Triple-negative patients more frequently received corticosteroids (79.3% vs 67.9%, p=0.003), cyclophosphamide (43.4% vs 26%, p<0.001) and azathioprine (38.5% vs 22.3%, p=0.002), while less frequently received prostanoids (71.6% vs 85.9%, p<0.001), calcium channel blockers (80.1% vs 87.7%, p=0.005) and phosphodiesterase-5 inhibitors (4% vs 20%, p<0.001). A higher prevalence of myopathy and interstitial lung disease and a reduced vascular burden were found in the triple-negative patients, suggesting that the non-specific and non-routinely tested autoantibodies may identify an SSc endotype resembling sclero-myositis.