Polymyositis/dermatomyositis Research Articles

Coexistence of anti-KS and anti-TIF1-γ antibodies in clinically amyopathic dermatomyositis presenting with rapid progression of interstitial lung disease.

Polymyositis/Dermatomyositis (PM/DM) is an idiopathic inflammatory myopathy (IIM) manifesting mainly as symmetrical proximal muscle weakness and/or typical cutaneous features due to autoimmune mechanisms. Clinically amyopathic dermatomyositis (CADM) is a subset of DM that exhibits only the typical cutaneous features without any clinical muscle symptoms. Several autoantibodies have been found specifically in patients with PM/DM, including CADM patients. Anti-KS antibody is one of a group of anti-aminoacyl transfer RNA (ARS) antibodies that are mainly associated with fever, Raynaud's phenomenon, polyarthritis, and interstitial lung disease (ILD), whereas anti-TIF1-γantibody is frequently found in DM patients with malignancy. Here, we report a CADM patient having both anti-KS antibody and anti-TIF1-γantibody. This patient developed an acute exacerbation of ILD and was successfully treated with high dose corticosteroid pulse therapy together with immunosuppressive agents. Although earlier experience had indicated that the seminal characteristic of anti-KS-positive ILD was slowly developing disease onset with little or no progression over the clinical course, the present patient suffered rapidly progressive disease.

Predictors of relapse of polymyositis/dermatomyositis associated interstitial lung disease.

Polymyositis/dermatomyositis (PM/DM) patients often develop interstitial lung disease (ILD), which can lead to relapse despite anti-inflammatory treatments. This study aims to elucidate the clinical characteristics of relapses in PM/DM-associated ILD patients. We gathered clinical data, including laboratory results, pulmonary function tests, chest high-resolution computed tomography findings from patients treated at Okinawa Chubu Hospital between January 1, 2010 and December 31, 2018. We identified a total of 74 patients, comprising 21 men and 53 women. Among them, 38 patients remained relapse-free with maintenance therapy, while 36 experienced relapses despite immunosuppressive management. We followed these patients until June 30, 2023, and 13 patients died. The median survival period was 51.4 months (range, 0.3-214 months). When comparing clinical variables, relapsed patients tended to be younger (49.9 vs. 64.1 years), reported myalgia and rash more frequently (63.9% vs. 28.9% and 61.15% vs. 21.1%, respectively). In terms of laboratory findings, lactate dehydrogenase (LDH) levels were higher in relapsed patients (613±464 vs. 381±203 U/L). Radiological findings showed that ground glass opacity (GGO) was more prevalent in relapsed patients (58.3% vs. 16.7%). A Cox-proportional hazards model for relapse demonstrated that serum LDH [hazard ratio (HR) 1.005, 95% confidence interval (CI): 1.000-1.009, P=0.02] and GGO (HR 1.863, 95% CI: 1.103-3.147, P=0.02) were valuable predictors of relapse. Receiver operating characteristic curve analysis of serum LDH indicated that a threshold of 450 correctly classified relapse in PM/DM-associated ILD patients. Serum LDH and GGO may serve as predictors of relapse in PM/DM-associated ILD patients.

Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other ANA-associated rheumatic diseases (AARDs) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. : This retrospective observational study included patients with AARDs such as SLE, SSc, SS, MCTD and PM/DM who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA) and titres. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. : The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52) and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titre is positive and the ncANA <320. Receiver operating characteristic analysis of the Cytoplasmic and ncANA range revealed an area under the receiver operating characteristic curve of 0.885 (95% CI: 0.844-0.927). : It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titre is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.

Glomerulonephritis as a renal manifestation in a patient with systemic sclerosis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis

Introduction and Importance: Systemic sclerosis (SSc) is a systemic immune disorder that may overlap with other rheumatologic disease; however, overlapping with antineutrophil cytoplasmic antibody-associated vasculitis is rare. Case Presentation: A 28-year-old Syrian male patient with SSc diagnosed according to the American College of Rheumatology/European League against Rheumatism 2013 criteria with a disease duration of 4 years, was admitted to the hospital complaining of palpable purpura in the lower limbs and hemoptysis and later, a rise in creatinine level. Laboratory tests showed high levels of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). The renal biopsy results were consistent with the diagnosis of glomerulonephritis. He was treated with methylprednisolone, cyclophosphamide, and rituximab, as he was diagnosed with SSc overlapping antineutrophil cytoplasmic antibody-associated vasculitis. Clinical Discussion: SSc most commonly renal manifestations are proliferative vasculopathy leading to scleroderma renal crisis. However, other types of renal involvement were also reported in SSc patients with comorbid autoimmune diseases such as glomerulonephritis and signs of concurrent vasculitis. SSc may overlap with rheumatoid arthritis, systemic lupus erythromatosus, polymyositis/dermatomyositis (PM/DM), and Sjogren Syndrome. Overlapping with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is mentioned in rare cases. The authors reported a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. Conclusion: The authors revealed a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. In SSc, renal involvement as glomerulonephritis is infrequent and should be detect in other rheumatologic disease such as systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis.

Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array.

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.

Distribution and clinical significance of anti-carbamylation protein antibodies in rheumatological diseases among the Chinese Han population.

Several studies have demonstrated that anti-carbamylation protein antibodies (Anti-CarPA) are persistent in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSC), primary Sjögren's syndrome (pSS), and interstitial lung disease associated with RA (RA-ILD). However, the relationship between anti-CarPA and other rheumatic diseases (RDs) and non-RA-ILD is not known till now. This study sought to examine the presence of anti-CarPA in Chinese Han patients with RDs and its clinical significance. The study included 90 healthy controls (HCs) and 300 patients with RDs, including RA, SLE, polymyositis/dermatomyositis (PM/DM), pSS, SSC, spondyloarthritis (SpA), anti-neutrophil cytoplasmic autoantibodies associated with vasculitis (AAV), undifferentiated connective tissue disease (UCTD), and Behcet's disease (BD). Antibodies against carbamylated human serum albumin were detected using commercial enzyme-linked immunosorbent assay kits. Correlations between clinical and laboratory parameters were analyzed. Serum levels of anti-CarPA in RA (34.43 ± 33.34 ng/ml), SLE (21.12 ± 22.23 ng/ml), pSS (16.32 ± 13.54 ng/ml), PM/DM (30.85 ± 17.34 ng/ml), SSC (23.53 ± 10.70 ng/ml), and UCTD (28.35 ± 21.91 ng/ml) were higher than those of anti-CarPA in the HCs (7.30 ± 5.05 ng/ml). The concentration of serum anti-CarPA was higher in patients with rheumatic disease-related interstitial lung disease (RD-ILD), especially RA-ILD, PM/DM-ILD, and pSS-ILD. Patients with RD-ILD who tested positive for anti-CarPA were more likely to have a more severe radiographic classification (grades II, p = 0.045; grades III, p = 0.003). Binary logistic regression analysis suggested that anti-CarPA had an association with ILD in RA (p = 0.033), PM/DM (p = 0.039), and pSS (p = 0.048). Based on receiver operating characteristics (ROC) analysis, anti-CarPA cutoffs best discriminated ILD in RA (>32.59 ng/ml, p = 0.050), PM/DM (>23.46 ng/ml, p = 0.038), and pSS (>37.08 ng/ml, p = 0.040). Moreover, serum levels of anti-CarPA were correlated with antibodies against transcription intermediary factor 1 complex (anti-TIF1) (R = -0.28, p = 0.044), antibodies against glycyl-transfer ribonucleic acid synthetase (anti-EJ) (R = 0.30, p = 0.031), and antibodies against melanoma differentiation-associated gene 5 (anti-MDA5) (R = 0.35, p = 0.011). Serum anti-CarPA could be detected in patients with RA, PM/DM, pSS, SSC, and UCTD among the Chinese Han population. And it may also assist in identifying ILD in patients with RA, PM/DM, and pSS, which emphasized attention to the lung involvement in anti-CarPA-positive patients.

Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor

BackgroundInterstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition.Case presentationA 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections.ConclusionsThis case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.

Risk factors analysis and prediction model establishment of malignant tumor in patients with polymyositis/dermatomyositis

Objective: To analyze the risk factors of polymyositis/dermatomyositis (PM/DM) complicated with malignant tumor and to construct clinical prediction model. Methods: A total of 427 PM/DM patients, who were admitted to Rheumatism Immunity Branch, the Second Affiliated Hospital, Air Force Medical University from January 1, 2015 to January 1, 2021, were enrolled in the study, including 129 males and 298 females. The mean age was (51.4±12.2) years. The patients were divided into control group (without malignant tumor, n=379) and case group (with malignant tumor, n=48) according to whether they were complicated with malignant tumors. In the two groups, 70% of the patients' clinical data were randomly selected as the training set data, and the remaining 30% were used as the validation set data. The clinical parameters were retrospectively collected, and risk factors of PM/DM complicated with malignant tumor were analyzed by binary logistic regression. R software was used to construct a clinical prediction model for malignant tumors in PM/DM patients using training set data. Validation set data were used to assess the feasibility of the model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive ability, accuracy and clinical applicability of the nomogram model. Results: The age of the control group was (50.4±11.8) years, and males accounted for 26.9%(102/379); the age of the case group was (59.1±12.7) years, and the proportion of males was 56.3% (27/48). The proportion of male, age, the positive rate of anti-transcription mediator 1-γ (TIF1-γ) antibody, glucocorticoid therapy resistance, and levels of creatine kinase (CK), carbohydrate antigen 125(CA125) and carbohydrate antigen 199 (CA199) were all higher in the case group than those in control group, while incidence of interstitial lung disease (ILD), arthralgia, Raynaud's phenomenon, serum albumin (ALB) level and lymphocyte (LYM) count were all lower than those in control group (all P<0.05). Binary logistic regression analysis showed that male (OR=2.931, 95%CI: 1.356-6.335), glucocorticoid therapy resistance (OR=5.261, 95%CI: 2.212-12.513), older age (OR=1.056, 95%CI: 1.022-1.091), elevated CA125 (OR=8.327, 95%CI: 2.448-28.319) and positive anti-TIF1-γ antibody (OR=7.529, 95%CI: 2.436-23.270) were risk factors of malignancy in PM/DM patients (all P<0.05); and complicated with ILD (OR=0.261, 95%CI: 0.099-0.689), complicated with arthralgia (OR=0.238,95%CI:0.073-0.779), elevated LYM count (OR=0.267, 95%CI: 0.103-0.691) were protective factors of malignancy in PM/DM patients (all P<0.05). The AUC of ROC curve predicting malignancy in PM/DM patients with the training concentrated prediction model was 0.887 (95%CI: 0.852-0.922), with a sensitivity of 77.9% and a specificity of 86.3%; it was 0.925 (95%CI: 0.890-0.960), 86.5% and 88.0% in the validated centralized prediction model, respectively. The correction curves of the training set and the validation set indicated that the predictive model had good calibration ability. Both the DCA curves of the training set and the validation set showed that the proposed predictive model had good clinical applicability. Conclusions: Older age, male, glucocorticoid therapy resistance, not complicated with ILD and arthralgia, elevated CA125, positive anti-TIF1-γ antibody, decreased LYM count are risk factors for malignancy in PM/DM patients, and the established nomogram model shows good predictive ability.

The Etiopathogenesis and Genetic Factors in Idiopathic Inflammatory Myopathies: A Review Article

Introduction: Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic autoimmune diseases characterized by muscle inflammation from unknown causes resulting in chronic weakness. Recent studies have shown the role of the cellular immune response affecting muscle fibers in polymyositis (PM), inclusion body myositis, and to a lesser extent, dermatomyositis (DM), wherein humoral immunity is more involved. The value of genetic factors of the class II major histocompatibility complex (MHC II) has also been highlighted. In studies of murine models, the presence of HLA-DR3 favors a higher risk of developing inflammatory muscle disease, including PM and juvenile DM. In recent years, few studies have provided timely information regarding this, thus the researchers initially proposed a review of existing literature to broaden the context regarding what was described and to visualize proposals that may enhance the understanding of this group of inflammatory pathologies. Methods: The design, implementation, analysis, and reporting of this study were followed according to the search with MeSH terms (Autoimmune myopathy, Inflammatory myopathies, Idiopathic inflammatory myopathies AND Major histocompatibility complex and genetics). We analyzed 12 articles for this review article. Conclusion: In the etiopathogenesis of IIM, both humoral and cellular immunity are observed, considering the presence of a trigger that causes the immune response. As for the immunogenetics, this review highlights what has been reported in Chinese and Mexican populations, where HLADRB1*09:01 is related to the presence of DM, and is observed as the first variant identified in various populations. This increases interest in this allele in the particular case to study DM and strengthens research that proposes the study of IIM independently for each nosological entity.

The Etiopathogenesis and Genetic Factors in Idiopathic Inflammatory Myopathies: A Review Article

Introduction: Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic autoimmune diseases characterized by muscle inflammation from unknown causes resulting in chronic weakness. Recent studies have shown the role of the cellular immune response affecting muscle fibers in polymyositis (PM), inclusion body myositis, and to a lesser extent, dermatomyositis (DM), wherein humoral immunity is more involved. The value of genetic factors of the class II major histocompatibility complex (MHC II) has also been highlighted. In studies of murine models, the presence of HLA-DR3 favors a higher risk of developing inflammatory muscle disease, including PM and juvenile DM. In recent years, few studies have provided timely information regarding this, thus the researchers initially proposed a review of existing literature to broaden the context regarding what was described and to visualize proposals that may enhance the understanding of this group of inflammatory pathologies. Methods: The design, implementation, analysis, and reporting of this study were followed according to the search with MeSH terms (Autoimmune myopathy, Inflammatory myopathies, Idiopathic inflammatory myopathies AND Major histocompatibility complex and genetics). We analyzed 12 articles for this review article. Conclusion: In the etiopathogenesis of IIM, both humoral and cellular immunity are observed, considering the presence of a trigger that causes the immune response. As for the immunogenetics, this review highlights what has been reported in Chinese and Mexican populations, where HLADRB1*09:01 is related to the presence of DM, and is observed as the first variant identified in various populations. This increases interest in this allele in the particular case to study DM and strengthens research that proposes the study of IIM independently for each nosological entity.

Elevated platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with polymyositis/dermatomyositis: a retrospective study.

This study aimed to examine the diagnostic and prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in patients with polymyositis/dermatomyositis (PM/DM). Clinical data of 200 patients with PM/DM and 204 healthy controls were retrospectively reviewed. We examined whether the PLR and NLR were associated with PM/DM. The PLR and NLR were higher in patients with PM/DM than in controls (both P < 0.001). The PLR and NLR were higher in patients with DM than in those with PM (both P < 0.01). The PLR was higher in the anti-melanoma differentiation-associated protein-5 (anti-MDA5) + PM/DM group than in the anti-MDA5- PM/DM group (P = 0.002). The NLR in non-survivors was higher than that in survivors (P = 0.01). The NLR was positively correlated with the occurrence of interstitial lung disease (ILD). The PLR and NLR were independent predictors of PM/DM, as well as risk factors (both P < 0.001). Moreover, the NLR had a predictive value for PM/DM-ILD and was closely related to mortality (P = 0.033, P = 0.003, respectively). Patients with PM/DM have a higher NLR and PLR than healthy controls, especially in those with anti-MDA5+. The PLR and NLR are independent risk factors for PM/DM and have some predictive value. The NLR is correlated with ILD and associated with an increased risk of mortality in patients with PM/DM. The NLR and PLR may be simple, economical, and accurate diagnostic and prognostic markers for patients with PM/DM. Key points • The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied in numerous inflammatory diseases as potential markers, but their clinical significance in polymyositis/dermatomyositis (PM/DM) remains unclear. • We examined the changes in the NLR and PLR between patients with PM/DM and healthy controls, as well as their association with mortality, interstitial lung disease, and anti-melanoma differentiation-associated protein-5. • Patients with PM/DM may benefit from using the NLR and PLR as simple, economical, and accurate diagnostic and prognostic markers.

Clinical Characteristics and Associated Factors for Infection and in-Hospital Mortality in Inpatients with Polymyositis/Dermatomyositis in China: A Retrospective Study.

To investigate the clinical features of infection, and associated factor for in-hospital mortality in a southern Chinese cohort with polymyositis/dermatomyositis (PM/DM). Clinical data were retrospectively reviewed from 2015 to 2022 from a tertiary hospital in southern China. Associated factors for infection and in-hospital mortality were analyzed by multivariate logistic regression analysis. A total of 554 patients with PM/DM were included, and 35.6% (197/554) of them developed 404 episodes of infection. Half of the patients developed infection within 4 months after disease onset. Bacterial infection was predominant (249/404, 61.6%). Lung was the most involved (242/404, 59.9%). Gram-negative bacteria the leading pathogens (64/84, 76.2%). Patients with anti-MDA5 positive were prone to develop severe infections (35.1% vs 16.4%, P<0.001) and had higher mortality (11.7% vs 3.4%, P=0.01). The in-hospital mortality was 6.5% (36/554). Infection was the leading cause of death (20/36, 55.6%). Older age (adjusted odds ratio (OR): 1.05, 95% confidential interval (CI): 1.02-1.09, P=0.004), ILD (adjusted OR: 2.76, 95% CI: 1.11-6.84, P=0.03), number of episodes of infection (adjusted OR: 1.91, 95% CI: 1.53-2.38, P<0.001), and elevated serum creatinine (Scr) (adjusted OR: 6.83, 95% CI: 1.77-26.40, P=0.01) were associated with in-hospital mortality. Infection is an early complication in PM/DM with a high proportion of lung involvement and predominance of gram-negative bacteria. It is a major contributor to in-hospital mortality. Older age, ILD, and number of episodes of infection are associated with poor prognosis.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

A rare case of multiple autoimmune syndrome after sars-cov2 infection

Mixed Connective Tissue Disease (MCTD) is a complex clinical entity, which includes features of Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Systemic Sclerosis (SSc) and Polymyositis/Dermatomyositis (PM/DM), along with the presence of a distinctive antibody, anti-U1-Ribonucleoprotein (RNP). Autoimmune hepatitis is a chronic inflammatory disease of the liver. It is characterized by increase in transaminase and immunoglobulin G levels, the presence of autoantibodies, and portal inflammatory infiltrate with interface hepatitis at liver biopsy. Primary biliary cholangitis is a chronic inflammatory autoimmune liver disease that is characterized by a positive antimitochondrial antibodies test and consequent progressive destruction of the small intrahepatic bile duct. Many reports have confirmed the development of autoimmune diseases after SARS-CoV-2 infection.Here we report the case of a 64-year-old woman, with a positive medical history for SARS-CoV2 infection, who was admitted to our Internal Medicine Unit “Cesare Frugoni”, Policlinico Hospital, Bari, in January 2022, and diagnosed with an extremely rare Multiple Autoimmune Syndrome (MAS), consisting in Mixed connective tissue disease, autoimmune hepatitisand primary biliary cholangitis.

Thymus variants on imaging of patients with primary Sjögren’s syndrome and polymyositis/dermatomyositis: clinical and immunological significance

We investigated the presence of radiographic thymus variants using a scoring system and examined their association with clinical and immunological features in primary Sjögren’s syndrome (pSS) and polymyositis/dermatomyositis (PM/DM) patients. Cases of 72 patients with pSS and 47 with PM/DM were randomly selected from all visitors to our department who received chest CT scanning, excluding those with thymoma or thymic cyst, or age <30 years. We quantitatively interpreted and assessed thymus size and attenuation score in axial CT images. Thymic enlargement was identified in 16 (22.2%) pSS and 14 (29.8%) PM/DM patients. A thymus attenuation score ≥ 2 was seen in 11 (15.3%) pSS and 9 (19.1%) PM/DM patients. Thymic enlargement showed a significant association with the titre of rheumatoid factor in PM/DM patients. Thymic enlargement and score showed a significant association with body weight in pSS patients. Radiographic thymus variants are often observed in pSS and PM/DM patients, particularly in cases of PM/DM, and may suggest the role of an abnormal immune response in their pathogenesis.

S1569 Gender-Based Association of Celiac Disease With Systemic Lupus Erythematosus and Other Rheumatologic Conditions: Analysis From National Inpatient Database

Introduction: Celiac disease is an immune mediated disorder of the digestive system that often presents with extraintestinal manifestations. The association of celiac disease with dermatitis herpetiformis, Type I Diabetes, IgA deficiency and chromosomal defects like Turner’s and Down’s syndrome is well known. However, the association of rheumatological diseases with Celiac disease remains controversial, especially based on gender. The aim of our study was to examine the association of rheumatological diseases with Celiac disease, stratified by gender. Methods: All adult hospitalized patients from January 2016 to December 2019 in nationwide inpatient sample (NIS) were captured. The study population included all patients with a diagnosis of Celiac disease using ICD-10 codes (International Classification of Diseases, tenth edition). Those without Celiac disease were included as the Control group. We identified patients with a diagnosis of SLE (Systemic Lupus Erythematosus), RA (Rheumatoid Arthritis), Fibromyalgia, Polymyalgia Rheumatica (PMR), Polymyositis/Dermatomyositis (PM/DM), Sjogren syndrome and Psoriatic Arthritis (PsA) using ICD-10 codes. We used linear regression for comparing continuous variables and Chi-square test for categorical variables. The association between Celiac disease and rheumatological conditions was analyzed using multivariate logistic regression model. Results: Our study included a sample size of 122,238,462 patients, of which 158,910 (0.13%) patients had Celiac disease and 122,079,552 (99.87%) patients did not. In the study group, highest risk was seen with Sjogren in both males (aOR=7.41) and females (aOR=3.93), with P< 0.001, followed by PM/DM (aOR=4.44 in males and aOR=2.11 in females, P-value < 0.001) compared to the control group. We also noted a higher risk of Celiac with SLE (aOR=1.72), RA (aOR=1.34), Fibromyalgia (aOR= 2.09), PMR (aOR=1.65) and PsA (aOR=2.71), all with P< 0.001 (Figure, Table). Similarly in males, greater risk was seen with SLE (aOR=2.51), RA (aOR=1.34), fibromyalgia (aOR=2.59), PMR (aOR=1.52), and PsA (aOR, 2.63). Conclusion: There is a significantly greater association of Rheumatological conditions with Celiac disease, more so in males than in females. Although, more studies are warranted to determine the causal relationship, knowledge about the association between them can help with early diagnosis and better management of these patients.Figure 1.: Graph 1 Table 1. - Association of Celiac disease with Rheumatologic diseases Rheumatologic diseases Females Males Unadjusted odds ratio Adjusted odds ratioa Unadjusted odds ratio Adjusted odds ratioa SLE* 2.49b 1.72b 2.89b 2.51b Rheumatoid Arthritis 1.83b 1.34b 1.55b 1.34b Fibromyalgia 3.06b 2.09b 3.44b 2.59b Polymyalgia Rheumatica 1.65b 1.35b 1.65b 1.52b Polymyositis/dermatomyositis 2.86b 2.11b 4.51b 4.44b Psoriatic arthritis 2.71b 1.57b 3.32b 2.63b Sjogren 6.68b 3.91b 10.25b 7.37b *SLE- Systemic Lupus Erythematosus.aAdjusted for age, race, Elixhauser score and other rheumatologic conditions.bsignificant and/or P<0.001.

Serum MUC5AC protein levels are correlated with the development and severity of connective tissue disease-associated pulmonary interstitial lesions

BackgroundMucin 5AC (MUC5AC) and mucin 5B (MUC5B) are the major components of airway mucins. The expression levels of MUC5AC and MUC5B are related to connective tissue disease-associated interstitial lung disease (CTD-ILD) in the promoter region of MUC5AC and MUC5B and the relevant bronchoalveolar lavage fluid. However, the serum protein levels of MUC5AC and MUC5B have not been tested in CTD-ILD patients. In this study, we tested the serum levels of MUC5AC and MUC5B proteins in CTD-ILD patients and assessed their relationship with the occurrence and development of ILD.MethodsSerum samples were obtained from 168 CTD and 80 healthy participants from the First Affiliated Hospital of Xiamen University. The serum levels of MUC5AC and MUC5B proteins were measured by enzyme-linked immunosorbent assay.ResultsOf the 168 individuals with CTD, 70 had primary Sjögren’s syndrome (pSS), 64 had systemic sclerosis (SSc), and 34 had polymyositis/dermatomyositis (PM/DM). There were 116 cases with concurrent ILD; ILD scores were 1 (n=23), 2 (n=41), and 3 (n=52). Serum MUC5AC and MUC5B protein levels were considerably higher in CTD-ILD than CTD-only individuals or healthy controls (both p<0.005). Among the CTD subgroups, MUC5AC was higher in individuals with concurrent ILD than in those without ILD (all p<0.05). MUC5AC was positively correlated with ILD severity in all three CTD subgroups (all R>0.47 and all p<0.05). The MUC5B levels varied substantially between SSc and SSc patients with concurrent ILD (p=0.032) and were related to ILD severity only in PM/DM patients (R=0.346 and p=0.045).ConclusionMUC5AC is correlated with the occurrence and development of ILD, while MUC5B is associated with ILD diagnosis and severity in CTD subgroups. Serum MUC5AC levels present a definite diagnostic utility for CTD-ILD and as proxies for its severity.

Relationship Between Annual Airbornepollen Levels (1974–2014) and the Occurrence of Idiopathic Dilated Cardiomyopathy, Myasthenia Gravis, Polymyositis/ Dermatomyositis, and Vasculitis Syndrome Based on the National Registry Database of Specific Intractable Disease in Japan: A Retrospective Study

Background: In Japan, pollen counts increased between 1977 and 1987, including three peaks (1978-1980, 1982, 1984-1986) coinciding with Kawasaki disease (KD) outbreaks. KD and related diseases may be related to pollen exposure (PE). Methods and Results: To elucidate the effects of PE on outbreaks of intractable muscular diseases and vasculitis syndromes, we evaluated the annual occurrence of disorders in relation to pollen counts using data from a national database. Specifically, we evaluated the occurrence of idiopathic dilated cardiomyopathy (IDCM), myasthenia gravis (MG), polymyositis/dermatomyositis (PM/DM), Takayasu arteritis (TAK), granulomatosis with polyangiitis (GPA), and periarteritis nodosa (PAN). While we did not observe increased disease rates during the first pollen count peak (1978-1980), increased rates of all evaluated diseases were observed during the 1982 and 1984-86 peaks. Furthermore, simultaneous outbreaks coincided with 10pollen count peaks between 1988 and 2013. We observed significant correlations between the annual number of newly registered patients (nRPs) with IDCM, MG, PM/DM, and PAN and annual pollen levels (PL). Significant correlations were also observed between nRPs and the annual PL measured with a lag of 2 years for IDCM and GPA, 1–4 years for PAN, and 6 years for MG, PM/DM, TAK, GPA, and PAN. Conclusion: Data suggest that the cumulative effects of PE within 6 years prior to diagnosis might possibly trigger onset of muscular specific intractable diseases.

Clinical Features of Anti-Synthetase Syndrome Associated with Prognosis in Patients with Dermatomyositis and Polymyositis.

We evaluated whether the clinical features of anti-synthetase syndrome (ASA)—myositis, fever, arthritis, mechanic’s hand, Raynaud’s phenomenon and interstitial lung disease—are relevant to prognosis in patients with dermatomyositis/polymyositis (DM/PM). A retrospective analysis was performed to identify patients diagnosed with DM/PM according to Bohan and Peter criteria. Clinical information, laboratory data and the presence of ASA clinical features at disease diagnosis were searched, and the outcomes of all-cause mortality, intensive care unit admission and disease remission at 1 year were assessed. Among the 86 patients included, fever (36.0%) and interstitial lung disease (26.7%) were the most common ASA clinical features. During the follow-up, 12 patients experienced death, and 7 of the 12 deaths (58.3%) occurred within 3 months of DM/PM diagnosis. Mortality was more frequently observed in those presenting with fever than in those without (25.8% versus 7.3%, p = 0.024). Multivariable Cox proportional analysis revealed that male sex (hazard ratio [HR] 5.53, 95% confidence interval [CI] 1.65, 18.49, p < 0.01) and fever (HR 4.20, 95% CI 1.26, 14.01, p = 0.02) independently predicted mortality. The clinical impact of fever was consistent in both sexes. Fever could be a warning signal heralding the poor outcome of mortality in patients with DM/PM, especially in early disease phases.

Time-Dependent Analysis of Risk of New-Onset Heart Failure Among Patients With Polymyositis and Dermatomyositis.

To determine the risk and time trends of heart failure (HF) leading to hospitalization in individuals newly diagnosed as having polymyositis/dermatomyositis (PM/DM) relative to non-PM/DM controls at the general population level. A retrospective cohort study was conducted using data from a nationwide insurance database in Taiwan. Patients with incident PM/DM and without a history of HF were selected between 2000 and 2013. Unmatched and propensity score-matched cohorts were established separately. A multivariable Cox proportional hazards regression model was used to estimate the adjusted hazard ratio (HR) for the risk of HF in the unmatched cohort. In the propensity score-matched cohort, general population controls were selected and matched at a 1:1 ratio to the patients with PM/DM based on propensity scores, which accounted for the confounding factors of age, sex, index date (year) of first diagnosis, comorbidities, and medication usage. The cumulative incidence of HF was estimated using the Kaplan-Meier method. A stratified Cox proportional hazards model was used to calculate the HR for the risk of HF events at different follow-up time points among patients with PM/DM compared with non-PM/DM controls in the propensity score-matched cohort. In the unmatched cohort, the study assessed 2,025 patients with PM/DM and 196,109 general population controls. Results of multivariable Cox regression analysis, adjusted for age, sex, comorbidities, and medication usage, revealed a greater risk of HF leading to hospitalization in the PM/DM group than in the control group (adjusted HR 3.29, 95% confidence interval [95% CI] 2.60-4.18). After matching based on propensity score, a total of 1,997 pairs of PM/DM patients and general population controls were identified. In this propensity score-matched cohort, the cumulative incidence of HF in patients with PM/DM at 3 years, 5 years, and 10 years was 3.3%, 4.4%, and 7.4%, respectively. The absolute difference in HF risk in the PM/DM group compared with the control group was 1.8% at 3 years, 2.1% at 5 years, and 3.0% at 10 years. Compared with general population controls, patients with PM/DM exhibited an augmented risk of HF (HR 2.06, 95% CI 1.36-3.12). Analyses stratified according to follow-up time point revealed that the increased risk of HF persisted for up to 10 years after the PM/DM diagnosis. These results indicate that the risk of HF leading to hospitalization was increased in patients with PM/DM throughout the study period, supporting the need for greater vigilance in the monitoring of patients with PM/DM for the development of this potentially lethal complication.