Search Results (15)

Background: The prevalence of pulmonary hypertension (PH) in patients who are positive for myositis-specific antibody (MSA) and myositis-associated antibody (MAA) remains unclear. Methods: We conducted a retrospective study of patients with an age of 18 years or older diagnosed with myositis interstitial lung disease (ILD) at our university’s ILD clinic between 2019 and 2022. Echocardiographic PH was defined by tricuspid regurgitation velocity (TRV) ≥ 2.9 m/s on transthoracic echocardiography (TTE) consistent with intermediate probability of PH using 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. We grouped patients based on low probability of PH vs. intermediate to high probability of PH. We examined 6 min walk test (6MWT) data, pulmonary function tests (PFTs), all-cause mortality, and rate of lung transplantation. We also evaluated patients who were on immunosuppression vs. those not on immunosuppression. Results: The intermediate to high probability of PH group had a higher prevalence of dermato-specific antibodies (14.2% vs. 34.5%, p = 0.048). Specifically, MDA-5 was found to be more prevalent in patients with intermediate to high probability of PH (7.1% vs. 24.1%, p = 0.040). There was no difference in 6MWT parameters between groups (363.2 ± 115.6 m vs. 294.9 ± 147.5 m, p = 0.108). FVC and DLCO were lower in patients with intermediate to high probability of PH (71.3 ± 22.4 L vs. 58.8 ± 16.7 L, p = 0.037; 56.3 ± 21.8 mL/min/mmHg vs. 36.9 ± 15.5 mL/min/mmHg, p = 0.003). The all-cause mortality and rate of lung transplantation was higher in the intermediate to high probability of PH group (5.4% vs. 20.7%, p = 0.041, 0% vs. 6.9%, p = 0.049). There was no difference in all-cause mortality between patients who were on immunosuppression vs. those who were not on immunosuppression in patients with intermediate to high probability of PH (33.3% vs. 7.1%; p = 0.169). Conclusions: Patients with MSA/MAA may have an increased risk of PH with reduced lung function, higher mortality, and greater rate of lung transplantation. Our study further elucidates the growing body of evidence that dermato-specific antibodies, such as MDA-5 are associated with an increased risk of PH. Further research is needed to investigate the role of PH and immunosuppression in these patients. Full article

Background: Pulmonary involvement is the most common prognosis-related organ involvement in idiopathic inflammatory myopathy (IIM). Owing to the large number of antibodies, the evidence for lung involvement and rare antibodies is limited. In everyday clinical practice, the interpretation of positive myositis antibodies represents a challenge. Methods: This study is a retrospective monocentric analysis. The data collection regarding positive myositis antibodies and possible pulmonary involvement was carried out from July 2019 to May 2022. Data analysis revealed positive results for one of the following antibodies: EJ, PL7, OJ, PL12, Mi-2α, TIF1γ, MDA5, SAE, NXP2, SRP, Ku, PM-Scl100 and PM-Scl75. In our analysis, patients with IIM, patients with inflammatory rheumatic disease other than IIM and patients without inflammatory rheumatic disease are described. The results of high-resolution computed tomography (HRCT), pulmonary function tests, echocardiographic examinations and their associated clinical findings are examined. Results: In the entire cohort, 209 patients with positive myositis antibodies were detected. In total, 22 (10.5%) patients had interstitial lung disease (ILD) patterns on HRCT. In the subgroup of patients with IIM, a significantly higher proportion of patients with lung involvement (n = 13, 35.1%) was found than in the group with other inflammatory rheumatic diseases (IRDs) (n = 6, 6.7%) or in the group without IRDs (n = 3, 3.7%). When the antibody groups were considered, the PL12-positive patients had the largest proportion of ILD (42%), followed by the MDA5-positive patients (40%). Conclusions: In patients with IIM, myositis antibodies are highly relevant for assessing the risk of lung involvement. In groups with other IRD or without IRD, antibody detection does not represent this high relevance for lung involvement. A differentiated assessment of the various MSAs or MAAs detected, as well as clinical parameters, allows for further important risk assessment for prognosis-relevant lung involvement. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

Background: Idiopathic inflammatory myopathies (IIMs), also known as myositis, are systemic autoimmune diseases characterized by chronic inflammation affecting the skin, muscles, and internal organs. Besides traditional risk factors and immune-mediated myocarditis, continuous activity of the immune system increases cardiovascular disease (CVD) risk, meaning that cardiovascular events are the leading causes of mortality in IIM patients. Statins are the most widely used lipid-lowering therapies, which reduce cardiovascular risk, but the fear of adverse muscular events inhibits the frequency of use. Methods: Our aim was to assess the CVD risk in a myositis cohort using the SCORE2 prediction system, carotid artery Doppler ultrasound measurement, and biomarkers; recommend individual lipid-lowering treatment; and follow the efficacy and adverse events of therapy in a 6-month treatment period. Results: The study population (80 IIM patients) was a middle-aged, female-dominant myositis cohort with an average disease duration of 9 years and low median global disease activity. Based on the SCORE2 evaluation, 78.8% of patients had medium/high CVD risk, while 73.13% had asymptomatic carotid plaque. After 6 months of adequate lipid-lowering therapy, 37.5% of patients reached a lower CVD risk category, the biomarker levels of atherosclerosis significantly decreased, and no progression in carotid plaques was detected. None of the patients reported an adverse muscular event or IIM relapse. Conclusions: Our findings proved that the CVD risk of patients with myositis is high, but carefully applied lipid-lowering treatment is the key to effective risk reduction. Risk stratification and the recommendation of preventive treatment are the responsibility of the treating physician. Full article

Cutaneous lesions suggestive of vasculitis and/or ischemic dermatopathy (ID) are anecdotally reported in canine leishmaniosis, and the clinicopathological features of these conditions have not been fully characterized. The objective of this case series was to describe six dogs with leishmaniosis and ID. In 5/6 dogs, leishmaniosis was diagnosed at the time of ID diagnosis, whereas in 1/6 dogs, ID developed during the first month of anti-Leishmania conventional treatment. One each of greyhound, Chihuahua, whippet, American bully, hound and mixed breeds were represented, and the median age at presentation was 6 years [2–8]. All patients presented high or very high levels of circulating anti-Leishmania infantum antibodies. The cutaneous lesions were multifocal alopecia with atrophic skin with hyper- or hypopigmentation (6/6), ulcers located on the extremities and trunk (3/6) and onychodystrophy (2/6). Histologically, ID was confirmed by the presence of follicular atrophy (faded follicles) (6/6), perivascular or interstitial lymphoplasmacytic dermatitis or panniculitis (6/6), collagen smudging (3/6), dermal fibrosis (3/6), lymphocytic interface dermatitis (3/6) and ulceration (3/6). Vasculopathy was observed in the superficial and mid-vascular plexuses in 4/6 dogs and characterized by the combination of some of the following lesions: vasocongestion, hemorrhagic foci, mild hyaline mural degeneration, thrombi and fragmented degenerating nuclear debris of neutrophils in the vascular wall. Moreover, myositis was observed in 1/6 cases. Leishmania-specific immunohistochemistry was positive in the skin of 4/6 cases. Leishmaniosis might be considered an underlying cause of ID in dogs. However, the immune mechanisms and pathogenesis need to be elucidated. Full article

Anti-synthetase syndrome (ASS) is a rare autoimmune disease. Since the knowledge of ASS remains limited, we conducted the retrospective study aiming to describe clinical characteristics and identify variables associated with interstitial lung disease (ILD) and mortality among patients with ASS. Patients diagnosed with ASS from January 2013 to October 2022 were included. Patient demographics, clinical manifestations, myositis auto-antibody profiles, HRCT findings, and laboratory tests were collected. Variables associated with mortality risk and ILD were evaluated using the Cox proportional hazards model and the logistic regression model, respectively. A total of 82 patients with ASS were included. Clinical manifestations included arthritis (57%), Raynaud’s phenomenon (32%), mechanic’s hands (29%), fever (26%), and myositis (17%). The myositis auto-antibody profiles included anti-PL-7 (29%), anti-Jo-1 (27%), anti-EJ (17%), anti-PL-12 (16%), and anti-OJ (11%). ILD was observed in 64 patients (78%). Among patients with ILD, 21 initially presented with ILD before developing other ASS clinical manifestations, 29 simultaneously presented with ILD and other symptoms, and 14 had isolated ILD throughout follow-up. Overall, 6 patients presented with rapid-progressive ILD. With a median follow-up time of 2.5 years, mortality was observed in 10 patients (12.2%). Factors associated with mortality included increased lymphocyte counts (adjusted HR, 0.74; 95% CI, 0.61–0.91; p < 0.01), isolated ILD (adjusted HR, 9.59; 95% CI, 1.52–60.61; p = 0.02) and the presence of anti-Ro52 antibodies (adjusted HR, 0.14; 95% CI, 0.02–0.93; p = 0.04). Factors associated with ILD included age (adjusted OR, 1.10; 95% CI, 1.03–1.18; p = 0.01), presence of anti-Ro52 antibodies (adjusted OR, 17.92; 95% CI, 2.13–138.68; p = 0.01), and presence of arthritis (adjusted OR, 0.09; 95% CI, 0.01–0.75; p = 0.03). Our study demonstrated a favorable overall mortality rate among ASS patients. Full article

Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles. In this study, 18 DM, 12 IMNM, 6 AS, 6 IBM, and 6 histologically normal muscle biopsies underwent miRNA profiling using the NanoString nCounter system. Eleven miRNAs were exclusively differentially expressed in DM compared to controls, seven miRNAs were only differentially expressed in AS, and nine miRNAs were specifically upregulated in IBM. No differentially expressed miRNAs were identified in IMNM. We also analyzed miRNA-mRNA associations to identify putative targets of differentially expressed miRNAs. In DM and AS, these were predominantly related to inflammation and cell cycle progression. Moreover, our analysis showed an association between miR-30a-3p, miR-30e-3p, and miR-199b-5p downregulation in DM and the upregulation of target genes induced by type I interferon. In conclusion, we show that muscle biopsies from DM, AS, and IBM patients have unique miRNA signatures and that these miRNAs might play a role in regulating the expression of genes known to be involved in IIM pathogenesis. Full article

Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to evaluate the prevalence of Myositis-Specific and Myositis-Associated Antibodies (MSA/MAA) in a cohort of FM patients. We enrolled 233 consecutive FM patients (defined according to the 2016 criteria) that did not report clinical signs of autoimmune disorders and followed them for at least one year. The patients were tested for MSA/MAA with immunoblotting. FM patients were seropositive for Antinuclear Antibodies (ANA) in 24% of cases, for MSA in 9%, and for MAA in 6%. A specific diagnosis of CTD was made in 12 patients (5.2%), namely, 5 cases of primary Sjögren’s Syndrome and 7 of Idiopathic Inflammatory Myopathy. Seropositive patients showed clinical features similar to those who were seronegative at baseline. A CTD diagnosis was associated with ANA positivity (p = 0.03, X² 4.9), the presence of a speckled pattern (p = 0.02, X² 5.3), positivity for MAA (p = 0.004, X² 8.1), and MSA (p = 0.003, X² 9.2). In conclusion, a non-negligible proportion of FM patients may be seropositive for MSA/MAA, and that seropositivity might suggest a diagnosis of CTD. Full article

We present a case of a 31-year-old patient with type 1 diabetes diagnosed at the age of 6. Diabetes is complicated with neuropathy, retinopathy, and nephropathy. He has been admitted to the diabetes ward due to inadequate diabetes control. Gastroscopy and abdominal CT were performed, and gastroparesis was confirmed as an explanation for postprandial hypoglycemia. During hospitalization, the patient reported sudden pain localized on the lateral, distal part of his right thigh. The pain occurred at rest and was aggravated by movement. Diabetic muscle infarction (DMI) is a rare complication of long-lasting, uncontrolled diabetes mellitus. It usually occurs spontaneously, without any previous infection or trauma, and is often misdiagnosed clinically as an abscess, neoplasm, or myositis. DMI patients suffer from pain and swelling of the affected muscles. Radiological examinations, including MRI, CT, and USG, are most important for the diagnosis, assessing the extent of involvement and differentiating DMI from other conditions. However, sometimes a biopsy and histopathological examination are necessary. The optimal treatment has still not been determined. There is also a potential risk of DMI recurrence. Full article

Background: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis. Methods: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected. Results: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37–83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities. Conclusion: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods. Full article

Background: Foam rolling is a type of self-massage using tools such as foam or roller sticks. However, to date, there is no consensus on contraindications and cautions of foam rolling. A methodological approach to narrow that research gap is to obtain reliable opinions of expert groups. The aim of the study was to develop experts’ consensus on contraindications and cautions of foam rolling by means of a Delphi process. Methods: An international three-round Delphi study was conducted. Academic experts, defined as having (co-) authored at least one PubMed-listed paper on foam rolling, were invited to participate. Rounds 1 and 2 involved generation and rating of a list of possible contraindications and cautions of foam rolling. In round 3, participants indicated their agreement on contraindications and cautions for a final set of conditions. Consensus was evaluated using a priori defined criteria. Consensus on contraindications and cautions was considered as reached if more than 70% of participating experts labeled the respective item as contraindication and contraindication or caution, respectively, in round 3. Results: In the final Delphi process round, responses were received from 37 participants. Panel participants were predominantly sports scientists (n = 21), physiotherapists (n = 6), and medical professionals (n = 5). Consensus on contraindications was reached for open wounds (73% agreement) and bone fractures (84%). Consensus on cautions was achieved for local tissue inflammation (97%), deep vein thrombosis (97%), osteomyelitis (94%), and myositis ossificans (92%). The highest impact/severity of an adverse event caused by contraindication/cautions was estimated for bone fractures, deep vein thrombosis, and osteomyelitis. Discussion: The mechanical forces applied through foam rolling can be considered as potential threats leading to adverse events in the context of the identified contraindications and cautions. Further evaluations by medical professionals as well as the collection of clinical data are needed to assess the risks of foam rolling and to generate guidance for different applications and professional backgrounds. Full article

Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. Results. A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. Conclusions. Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management. Full article

Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O₂/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (−12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. −69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options. Full article

Toxoplasma gondii is a major protozoan parasite and infects human and many other warm-blooded animals. The infection leads to Toxoplasmosis, a serious issue in AIDS patients, organ transplant recipients and pregnant women. Neospora caninum, another type of protozoa, is closely related to Toxoplasma gondii. Infections of the protozoa in animals also causes serious diseases such as Encephalomyelitis and Myositis-Polyradiculitis in dogs or abortion in cows. Both Toxoplasma gondii and Neospora caninum have similar nucleoside triphosphate hydrolases (NTPase), NcNTPase and TgNTPase-I in Neospora caninum and Toxoplasma gondii, respectively. These possibly play important roles in propagation and survival. Thus, we targeted the enzymes for drug discovery and tried to establish a novel high-standard assay by a combination of original biochemical enzyme assay and fluorescent assay to determine ADP content. We then validated whether or not it can be applied to high-throughput screening (HTS). Then, it fulfilled criterion to carry out HTS in both of the enzymes. In order to identify small molecules having inhibitory effects on the protozoan enzyme, we also performed HTS using two synthetic compound libraries and an extract library derived from marine bacteria and then, identified 19 compounds and 6 extracts. Nagasaki University collected many extracts from over 18,000 marine bacteria found in local Omura bay, and continues to compile an extensive collection of synthetic compounds from numerous drug libraries established by Japanese chemists. Full article

The incidence of myositis in patients with systemic lupus erythematosus (SLE) is low among different series. Here we attempt to describe the main features of SLE/myositis overlap syndrome. We retrospectively reviewed the medical records of 174 patients with SLE seen over 15-year period. All the patients fulfilled the revised American Rheumatology Association criteria for SLE. Patients who met The Bohan and Peter criteria for definite myositis were included in this study. Among those patients, six patients had an associated myositis (3.4% overall). They were 6 women with a mean age of 29 years (20-41 years). At the initial evaluation, 3 patients (50%) were complained from myalgia, and all patients had symmetrical muscle weakness (proximal muscle weakness in 6 cases with distal muscle weakness in 2 cases). The muscle disease was severe in 1 case. Involvements of muscles of the pharynx and upper esophagus were noted in 4 patients (66.6%). The creatine kinase (CK) levels were elevated in 4 cases with a mean rate of 2153.5 UI/L. The electromyogram (EMG) revealed signs of myositis in 5 cases. Muscle biopsy, performed in 5 patients, revealed an inflammatory myopathy changes in 4 cases. Antinuclear antibodies (ANA) were positive in all cases. All our patients were treated with high doses of corticosteroids with favorable outcome. Relapse of SLE disease had occurred in 2 patients. The association SLEmyositis is rare with heterogeneous presentation. Through our observations and literature data we will specify the characteristics of this association. Full article