Pruritogenic molecules in the skin of patients with dermatomyositis.

Introduction: Pruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients. Methods: Interleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software. Results: A total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p < 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions. Discussion: Our results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.

Incidence, features, and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: Vaccination against coronavirus disease 2019 (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM); however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features, and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. METHODS: A cohort of 176 IIM patients were interviewed after the third wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). RESULTS: A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 mo, and 13/146 (8.9%) patients within 1 mo. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30 ± 15.81; seven minor, five moderate, and zero major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1 ± 19.53; 3 minimal, 8 moderate, and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p < .0001; odds ratio, 33; confidence interval, 9-120) was significantly associated with the occurrence of a relapse. DISCUSSION: A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare.

The effect of COVID-19 pandemic on idiopathic inflammatory myositis patients: a single centre experience.

OBJECTIVES: Pandemic caused by coronavirus disease (COVID-19) determines the life of clinicians and patients since 2 years. We have a lot of information about disease course, treatment and protection against virus, but less on the prognosis of infection in patients with idiopathic inflammatory myopathies (IIM). Also few data are available on triggered humoral response and side effects after vaccination. METHODS: Our goal was to assess by a retrospective cross-sectional study the above data in our cohort (176 IIM patients) by identifying COVID-19 positive patients and follow disease course. Incidence and complications of vaccination were determined by questionnaires. 101 patients volunteered for complex blood test. RESULTS: By June 1st, 2021 significantly higher incidence of COVID 19 infections (34.7%) were identified comparing to the national prevalence (8.2%). A third of these infections occurred asymptomatically or mild. Patients requiring hospitalisation had a significantly longer disease duration and a higher incidence of anti-Jo-1 antibody. All patients infected by COVID-19 became seropositive regardless the immunosuppressive therapy or symptoms severity. 54.3% of the patients received anti-COVID-19 vaccine. 72.3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfizer-BioNTech vaccination compared to others. Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment. No major post-vaccination infection was observed. CONCLUSIONS: Based on our results, myositis may be associated with an increased risk of COVID-19 infection. Independent risk factor for hospitalisation are longer disease duration and anti-Jo1 positivity. Anti-SARS-CoV2 vaccines seem safe and tolerable and strongly recommended for that population.

Clinical, Serological, and Genetic Characteristics of a Hungarian Myositis-Scleroderma Overlap Cohort.

Overlap myositis is a distinct subgroup of idiopathic inflammatory myositis (IIM) with various clinical phenotypes. The aim of this study was to determine the clinical, serological, and genetic features of systemic sclerosis (SSc)-IIM overlap patients. It was a retrospective study using clinical database of 39 patients, fulfilling both the criteria of SSc and IIM. 56.4% of the patients had limited cutaneous, 43.6% had diffuse cutaneous SSc, whereas 7.7% of the patients had dermatomyositis and 92.3% polymyositis. The two diseases occurred simultaneously in 58.97%, while 10.26% in myositis and 30.77% in scleroderma were initially diagnosed. The frequencies of organ involvement were interstitial lung disease 71.8%, dysphagia 66.7%, cardiac involvement 41%, pulmonary arterial hypertension (PAH) 30.8%, and renal involvement 12.8%, respectively. The presence of human leukocyte antigen (HLA) - DRB1∗03 and DQA1∗051∗01 alleles were significantly higher in the overlap patients than in healthy controls (82.35% vs. 27.54%; p < 0.0001 and 88.24% vs. 30.16; p < 0.0001). Certain clinical parameters, such as fever at diagnosis (41.67% vs. 7.41%, p = 0.0046), cardiac involvement (83.33% vs. 22.22%, p = 0.0008), subcutaneous calcinosis (41.66 vs. 11.11, p = 0.01146), and claw hand deformity (25% vs. 11.11%, p = 0.00016) were significantly associated with the presence of PAH. Upon comparison, the overlap patients and anti-Jo-1 positive antisynthetase patients showed similarities in terms of genetic results and major clinical features; however, SSc-IIM overlap patients could be distinguished with higher erythrocyte sedimentation rate (ESR) level, more frequent presence of Raynaud's phenomenon (p < 0.0001; OR: 20.00), dysphagia (p < 0.0001; OR: 15.63), and infrequent livedo reticularis (p < 0.01; OR: 0.11). SSc-IIM overlap myositis is a unique group within IIM-s possessing characteristic clinical features.

Bone Health in Idiopathic Inflammatory Myopathies: Diagnosis and Management.

PURPOSE OF REVIEW: This article provides an update on the most recent advances in epidemiology, pathogenesis, diagnostic procedures, and therapeutic approaches for myositis-associated bone diseases, such as osteoporosis and bone fractures. RECENT FINDINGS: In the recent years, several studies showed that osteoporosis and consequent fractures are a common and frequently underestimated complication in patients with idiopathic inflammatory myopathies (IIM). In younger patients, asymptomatic fractures might present in the early phase of the disease which could increase the risk of development of further fractures. High-risk patients could be selected with early application of combined diagnostic procedures, such as fracture risk scores with steroid dose adjustments and imaging. Recent advances might help clinicians from different fields of medicine in the early recognition and management of myositis-associated osteoporosis, which will potentially improve the quality of life of patients with IIM.

The risk of fracture and prevalence of osteoporosis is elevated in patients with idiopathic inflammatory myopathies: cross-sectional study from a single Hungarian center.

BACKGROUND: The prevalence of osteoporosis and risk of fractures is elevated in rheumatoid arthritis (RA), but we have limited information about the bone mineral density (BMD) and fracture risk in patients with inflammatory myopathies. We intended to ascertain and compare fracture risk, bone mineral density and the prevalence of vertebral fractures in patients with inflammatory myositis and rheumatoid arthritis and to assess the effect of prevalent fractures on the quality of life and functional capacity. METHODS: Fifty-two patients with myositis and 43 patients with rheumatoid arthritis were included in the study. Fracture Risk was determined using FRAX® Calculation Tool developed by the University of Sheffield. Dual energy X-ray absorptiometry and bidirectional thoracolumbar radiographs were performed to assess BMD and vertebral fractures. Quality of life was measured with Short Form-36 (SF-36) and physical function assessment was performed using Health Assessment Questionnaire (HAQ). RESULTS: We found a significantly elevated fracture risk in RA as compared to myositis patients if the risk assessment was performed without the inclusion of the BMD results. If BMD results and glucocorticoid dose adjustment were taken into account, the differences in fracture risk were no longer significant. The prevalence of osteoporosis was found to be significantly higher in the myositis group (7% vs. 13.5%, p: 0.045), but the fracture prevalence was similar in the two groups (75% vs. 68%). The fracture rates were independently associated with age in the myositis group, and with lower BMD results in the RA patients. The number of prevalent fractures was significantly correlated to poorer physical function in both groups, and poorer health status in the myositis group, but not in the RA group. CONCLUSIONS: Our findings suggest that inflammatory myopathies carry significantly elevated risks for osteoporosis and fractures. These higher risks are comparable to ones detected with RA in studies and strongly affect the physical function and quality of life of patients. Therefore further efforts are required to make the fracture risk assessment reliable and to facilitate the use of early preventive treatments.

Effect of Genetic and Laboratory Findings on Clinical Course of Antisynthetase Syndrome in a Hungarian Cohort.

The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynaud's phenomenon, 43% fever, 33% mechanic's hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.