Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. METHODS: This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. RESULTS: Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. CONCLUSIONS: Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Work situation, work ability and expectation of returning to work in patients with systemic autoimmune myopathies.

OBJECTIVES: To document the work situation, the work ability and the expectation of returning to work among adult patients with systemic autoimmune myopathies (SAMs), and to identify the factors associated with each of these outcomes. METHODS: Cross-sectional study. The work situation (performing paid work vs out of work) was ascertained via a structured questionnaire. For those who were working, we applied the Work Ability Index (WAI; scale 7-49); and for those who were out of work, we applied the Return-to-Work Self-Efficacy questionnaire (RTW-SE; scale 11-66). RESULTS: Of the 75 patients with SAMs included, 33 (44%) were doing paid work and 42 (56%) were out of work. The work situation was independently associated with physical function, assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). A 1-point increase in the HAQ-DI (scale 0-3) decreased the chance of doing paid work by 66% (95% CI: 0.16, 0.74; P = 0.007). Patients performing paid work had a mean WAI of 33.5 (6.9). The following variables were associated with a decrease in the WAI score in the regression model: female sex (-5.04), diabetes (-5.94), fibromyalgia (-6.40), fatigue (-4.51) and severe anxiety (-4.59). Among those out of work, the mean RTW-SE was 42.8 (12.4). Cutaneous manifestations and >12 years of education were associated with an average increase of 10.57 and 10.9 points, respectively, in the RTW-SE. A 1-point increase in the HAQ-DI decreased the RTW-SE by 4.69 points. CONCLUSION: Our findings highlight the poor work participation in a well-characterized sample of working-age patients with SAMs. Strategies to improve work-related outcomes in these patients are urgently needed.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome.

OBJECTIVES: Until now, researchers have not provided a well-defined muscle histological pattern for antisynthetase syndrome (ASSD). Therefore, we aimed to analyse the muscle biopsies of patients with anti-Jo-1 ASSD. METHODS: This study included 26 patients with anti-Jo-1 ASSD admitted for investigation of the disease and obligatorily with muscle impairment, from 2010 to 2021, whose serial frozen muscle sections were analysed. RESULTS: Patients' mean age at disease diagnosis was 42.8±11.6 years, and the female gender was most predominant. Concerning muscle biopsies, cell infiltrates were present in 76.9% of the samples, and they were mainly located at the endomysium area (70%), with a predominance of macrophages (92.9%). Fiber muscle necrosis was present in 92.3% and was diffused in 54.2%. Expression of MHC-I was seen in all samples. Samples were mostly marked by the presence of CD68+ and discreet/low CD4+ and CD8+ staining, which is consistent with a higher predominance of observed necrosis and macrophage cell infiltrates. In general, 38.5% of patients had a necrotising myopathy pattern in muscle biopsies, whereas 34.6% and 26.9% had a general inflammatory myopathy pattern and nonspecific myopathy, respectively. This necrotising myopathy pattern was not associated with the demographic, clinical, or laboratory data. CONCLUSIONS: Our data show that almost 40% of patients with well-defined anti-Jo-1 ASSD with objective muscle impairment have a necrotising myopathy pattern in their muscle biopsies. Although this pattern is more classically related to immune-mediated necrotising myopathies, in association with clinical manifestations and the presence of anti-Jo-1 autoantibodies, this characteristic may lead to ASSD diagnosis.

Transcranial direct current stimulation is safe and effective in autoimmune myopathies: a randomised, double-blind, sham-controlled trial.

OBJECTIVES: We aimed to assess the safety and efficacy of transcranial direct current stimulation (tDCS) in patients with systemic autoimmune myopathies (SAMs). METHODS: This prospective, randomised, sham-controlled, double-blind, study included 20 patients with SAMs allocated to receive sham or active tDCS (2mA, 20 minutes, 3 days). Electrodes were positioned with the anode over the C1 or C2, whereas the cathode was placed over the Fp2 or Fp1, respectively. The groups were evaluated in four periods with specific questionnaires and functional tests: pre-stimulation and after 30 minutes, three weeks, and eight weeks post-tDCS. RESULTS: Two patients from the sham group withdrew after the three sessions. The demographic data, type of myositis, disease duration, and disease status were comparable between the active and sham tDCS groups. After interventions, in the active tDCS group, the physical aspects of SF-36 in week eight, mean and better timed up-and-go test at each evaluation, peak torque of stimulated inferior limb extension improved significantly (p<0.05). The emotional aspect of SF-36 decreased only in the active tDCS group (p<0.001). The patients' adherence to the protocol was 100% and no serious adverse event was reported, including disease relapses. CONCLUSIONS: This study evidences the safety of tDCS, as well as its potential efficacy in improving muscle strength and function in SAMs patients. More studies with a larger sample and longer tDCS sessions are necessary to corroborate the results of the present study.

Long-term effects of early pulse methylprednisolone and intravenous immunoglobulin in patients with dermatomyositis and polymyositis.

OBJECTIVE: To evaluate the long-term effects of pulse i.v. methylprednisolone (IVMP) or IVIG administered during the first year of diagnosis in DM and PM patients. METHODS: This is a retrospective single-centre cohort study of patients with PM/DM followed for up to 4 years from 2001 to 2017. We used Cox regression models to estimate hazard ratios (HRs) and assess the effects of early pulse IVMP or IVIG on three outcomes: complete clinical response, CS discontinuation, and survival. Analysis was adjusted for clinical, laboratory and treatment covariates. RESULTS: A total of 204 patients were included and categorized into four initial treatment groups: pulse IVMP (n = 46), pulse IVMP + IVIG (n = 55), IVIG (n = 10), and without IVMP or IVIG (n = 93). The groups of early pulse IVMP and pulse IVMP + IVIG had a higher HR for complete clinical response in the multivariate models (HR = 1.56, 95% CI: 1.05, 2.33, P = 0.029; and HR = 1.58, 95% CI: 1.02, 2.45, P = 0.041, respectively). Only the group of pulse IVMP + IVIG had a significant association with CS discontinuation in the multivariate analysis (HR = 1.65, 95% CI: 1.02, 2.68, P = 0.043). Early pulse IVMP or IVIG had no impact on mortality. CONCLUSION: Despite having a more severe disease profile, patients with PM/DM submitted to pulse IVMP or pulse IVMP + IVIG during the first year of diagnosis had a higher HR for complete clinical response, whereas the combination of pulse IVMP + IVIG had an association with CS discontinuation. Prospective long-term studies are warranted to confirm these benefits of early pulse IVMP and IVIG on patients with PM/DM.

Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine.

OBJECTIVES: To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). METHODS: A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies-NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. RESULTS: Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0.001). Negative NAb was associated with older age (P = 0.015), RA (P = 0.002), SSc (P = 0.026), LEF (P = 0.016) and rituximab use (P = 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; P = 0.047), LEF (OR = 0.32, P = 0.036) and rituximab use (OR = 0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose. CONCLUSIONS: This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.

Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2.

OBJECTIVES: To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. METHODS: This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. RESULTS: Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT [7.9 (95%CI 4.7-13.2) vs 24.7 (95%CI 30.0-30.5) UA/ml, P<0.001] and frequency of NAb (51.4% vs 77.2%, P<0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4-83.4) vs 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P>0.05). CONCLUSION: Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. TRIAL REGISTRATION: COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698.

Analysis of patient-physician discrepancy in global assessment of systemic autoimmune myopathy disease activity.

OBJECTIVES: To compare the perception of disease activity (DA) between adult patients with systemic autoimmune myopathies (SAMs) and their physicians, and analyse possible sources of discordance. METHODS: This cross-sectional study included 75 patients with SAMs. Patients and physicians rated the global DA on a 0-10 cm visual analogue scale. A discrepancy score was calculated by subtracting physician assessment from patient assessment. Three groups were defined: (I) no discrepancy: difference within -2.0 to +2.0; (II) negative discrepancy (ND): difference <-2.0 (patient underrated DA in relation to physcian); (III) positive discrepancy (PD): difference >+2.0 (patient overrated DA in relation to physician). Logistic regression was used to identify predictors of discordance. RESULTS: Discordance in patient-physician assessment of DA was found in 21 (28%) cases. ND was observed in 3 (4%), PD in 18 (24%), and no discrepancy in 54 (72%) assessments. Due to the small number, ND cases were excluded from the analysis. PD was associated with older age, personal history of depression, past joint involvement, higher MMT-8 and lower extramuscular DA. In the regression model, for each additional year of age, the chance of PD increases, on average, by 9% (OR 1.09; 95%CI 1.01-1.17, p=0.034). Personal history of depression increases the chance of PD by 829% (OR 9.29; 95%CI 1.52-56.89, p=0.016). CONCLUSIONS: Almost 30% of patients had discordance in DA assessment from their physicians. The majority of them overrated their DA. These patients tend to be older and are more likely to have personal history of depression, past joint involvement, and milder disease.

Serum Myostatin and Follistatin Levels in Patients With Dermatomyositis and Polymyositis.

BACKGROUND: Myostatin is a protein in the TGF-ß family that negatively regulates muscle mass, and follistatin is a myostatin antagonist. OBJECTIVE: The aim of this study was to measure serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients and correlate these levels with muscle strength, fatigue, functional capacity, damage, and serum levels of muscle enzymes. METHODS: This was a multicenter cross-sectional study including 50 patients (34 dermatomyositis and 16 polymyositis [PM]) and 52 healthy individuals (control group [CG]). The disease status was evaluated according to the International Myositis Assessment & Clinical Studies. Fatigue was rated according to the Fatigue Severity Scale, and body composition was measured using dual-energy x-ray emission densitometry. Myostatin and follistatin were measured using enzyme-linked immunosorbent assays. RESULTS: Mean age was 50.9 ± 14.0 years, and mean disease duration was 89.2 ± 80.9 months. There were no differences in levels of myostatin (14.15 ± 9.65 vs. 10.97 ± 6.77 ng/mL; p = 0.131) or follistatin (0.53 ± 0.71 vs. 0.49 ± 0.60 ng/mL; p = 0.968) between patients and the CG. However, myostatin levels were higher in PM than CG (16.9 ± 12.1 vs. 11.0 ± 6.8 ng/mL; p = 0.036). There was no difference in serum myostatin among patients with and without low lean mass. Patients not treated with corticosteroids had higher serum levels of myostatin than the CG. There was a weak negative correlation between follistatin and Manual Muscle Testing and a Subset of Eight Muscles and a weak positive correlation between follistatin and Healthy Assessment Questionnaire. CONCLUSIONS: Serum levels of myostatin and follistatin did not differ between dermatomyositis and PM patients and control subjects. The assessment of serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients seems not to be helpful in clinical practice.

Acute cardiometabolic effects of brief active breaks in sitting for patients with rheumatoid arthritis.

Exercise is a treatment in rheumatoid arthritis, but participation in moderate-to-vigorous exercise is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. We compared the acute effects of active breaks in sitting with those of moderate-to-vigorous exercise on cardiometabolic risk markers in patients with rheumatoid arthritis. In a crossover fashion, 15 women with rheumatoid arthritis underwent three 8-h experimental conditions: prolonged sitting (SIT), 30-min bout of moderate-to-vigorous exercise followed by prolonged sitting (EX), and 3-min bouts of light-intensity walking every 30 min of sitting (BR). Postprandial glucose, insulin, c-peptide, triglycerides, cytokines, lipid classes/subclasses (lipidomics), and blood pressure responses were assessed. Muscle biopsies were collected following each session to assess targeted proteins/genes. Glucose [-28% in area under the curve (AUC), P = 0.036], insulin (-28% in AUC, P = 0.016), and c-peptide (-27% in AUC, P = 0.006) postprandial responses were attenuated in BR versus SIT, whereas only c-peptide was lower in EX versus SIT (-20% in AUC, P = 0.002). IL-1ß decreased during BR, but increased during EX and SIT (P = 0.027 and P = 0.085, respectively). IL-1ra was increased during EX versus BR (P = 0.002). TNF-α concentrations decreased during BR versus EX (P = 0.022). EX, but not BR, reduced systolic blood pressure (P = 0.013). Lipidomic analysis showed that 7 of 36 lipid classes/subclasses were significantly different between conditions, with greater changes being observed in EX. No differences were observed for protein/gene expression. Brief active breaks in sitting can offset markers of cardiometabolic disturbance, which may be particularly useful for patients who may find it difficult to adhere to exercise.NEW & NOTEWORTHY Exercise is a treatment in rheumatoid arthritis but is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. Our findings show beneficial, but differential, cardiometabolic effects of active breaks in sitting and exercise in patients with rheumatoid arthritis. Breaks in sitting mainly improved glycemic and inflammatory markers, whereas exercise improved lipidomic and hypotensive responses. Breaks in sitting show promise in offsetting aspects of cardiometabolic disturbance associated with prolonged sitting in rheumatoid arthritis.

Short- and Long-Term Outcome of Systemic Lupus Erythematosus Peripheral Neuropathy: Bimodal Pattern of Onset and Treatment Response.

BACKGROUND/OBJECTIVE: Our aim was to describe the short- and long-term outcome of peripheral neuropathy (PN) attributed exclusively to systemic lupus erythematosus (SLE). METHODS: Systemic lupus erythematosus patients with defined PN (clinical and electroneuromyography) were retrospectively evaluated at onset, 1-year, and 5-year follow-up using a standardized electronic chart database that started in 2000. Exclusion criteria were comorbidities, drugs, and infections. Age-, sex-, and disease duration-matched SLE patients without PN were selected as controls. RESULTS: Lupus PN was identified in 38 (1.8%) of 2074 patients, and almost two thirds had PN onset in the first 5 years of SLE (63.2%). Peripheral neuropathy SLE had higher frequencies of cutaneous vasculitis (50% vs 21.1%, p = 0.002), lymphopenia (60.5% vs 36.8%, p = 0.027), anti-Sm (52.6% vs 27.6%, p = 0.013), and higher SLEDAI-2K scores (11.5 ± 10.5 vs 4.9 ± 6.7, p < 0.001) compared with controls. The most common type was polyneuropathy (71.1%) with sensory-motor pattern (68.4%). At PN diagnosis, all patients received glucocorticoid and 97.4% started immunosuppressive therapy (50% intravenous cyclophosphamide, 42.1% azathioprine). After 1-year follow-up, 92.1% had a favorable outcome with complete (36.8%) or partial remission (55.2%), in parallel with a decrease in prednisone dose (48.3 ± 17.9 vs 15.3 ± 13.4 mg/d, p < 0.001), symptomatic therapy (57.9% vs 29.7%, p = 0.02), and SLEDAI-2K score (11.5 ± 10.5 vs 1.7 ± 3.7, p < 0.001). SLEDAI-2K scores were higher in patients who had PN onset with less than 1 year of SLE duration, compared with those with more than 5 years of disease (21.3 ± 9.1 vs 3.9 ± 5.3, p < 0.001). Early-PN-onset group had a better response to treatment (complete remission at 1-year follow-up 61.5% vs 25%, p = 0.039). At 5-year follow-up, 89.3% remained with complete/partial remission. CONCLUSIONS: Peripheral neuropathy attributed to SLE itself is a rare manifestation with a bimodal pattern, characterized by a predominant early-onset group associated with high disease activity and a higher rate of complete remission, and a late-onset group with low disease activity and a partial therapy response.

Serum interleukin-17A level is associated with disease activity of adult patients with dermatomyositis and polymyositis.

OBJECTIVES: To assess serum interleukin (IL)-17A levels in patients with dermatomyositis (DM) and polymyositis (PM) and correlate them with the demographic, clinical, laboratory and therapeutic data of these diseases. METHODS: This was a cross-sectional, single-centre study that included defined DM and PM patients who were age-, gender- and ethnicity-matched to healthy individuals. Serum IL-17A analysis, as well as analysis for other cytokines (IL-6, TNFα and IFNγ), was performed by multiplex immunoassay. The disease status parameters were based on the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. RESULTS: Eighty DM, 32 PM patients and 104 healthy individuals were enrolled. Mean age of patients with DM and PM was 46.0 and 47.7, respectively, with a predominance of women and white ethnicity in both groups. Overall, clinical, laboratory, therapeutic, and current disease status were similar among patients with DM and PM. Median serum IL-17A level was higher in patients with PM and DM than the control group (0.73 vs. 0.49 vs. 0.35 pg/mL, respectively; p<0.050) and higher in PM when compared to DM (p<0.001). In DM, serum IL-17A levels were associated with cumulative cutaneous lesions, IMACS parameters, and serum IL-6 and IFNγ levels. In PM, serum IL-17A levels correlated with patients' current age, IMACS parameters and serum TNFα and IFNγ levels. CONCLUSIONS: Serum IL-17A levels are not only increased, but also associated with disease activity in patients with DM and PM. Our data strongly suggest that IL-17A may be a biomarker of disease activity for these systemic autoimmune myopathies.

High prevalence of metabolic syndrome in antisynthetase syndrome.

OBJECTIVES: A high frequency of metabolic syndrome (MetS) has been recently described in different idiopathic inflammatory myopathies, but not in antisynthetase syndrome (ASS). Therefore, the aim of the present study was to determine the prevalence of MetS in ASS and also its possible association with cardiovascular the risk factors and ASS-related disease characteristics. METHODS: A cross-sectional single centre study of 42 consecutive ASS patients was conducted from 2012 to 2015 and compared to 84 healthy individuals matched for gender, age, ethnicity and body mass index-matched (control group). MetS was defined according to the 2009 Join Interim Statement. Clinical and laboratory data were assessed according to a standardised protocol. RESULTS: ASS patients had a median age of 41.1 years with a predominance of female gender and white race. ASS patients had a higher frequency of MetS (42.9% vs. 13.1%; p<0.001) as well as of insulin resistance than controls. Moreover, ASS patients had higher resistin, lower leptin and similar adiponectin levels in serum than controls. Further analysis of ASS patients with (n=18) and without (n=24) MetS revealed that older age at disease onset (48.7 vs. 35.4 years; p<0.001) was identified in those with the syndrome but were similar regarding disease duration, disease status, treatment, insulin resistance and serum adipocytokine levels. CONCLUSIONS: The prevalence of MetS was high in ASS patients that also had serum resistin and low leptin levels. As also identified in other idiopathic inflammatory myopathies, MetS in ASS is more prevalent in older patients.

Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.

OBJECTIVES: To evaluate leflunomide as an adjuvant drug in refractory dermatomyositis (DM) with primarily cutaneous activity. METHODS: A retrospective, single-centre, cohort study including 18 adult patients with DM (classical or clinically amyopathic DM) and cutaneous activity from 2001 to 2016 was conducted. Patients were dependent on glucocorticoid and refractory to at least two full-dose immunosuppressants/immunomodulators or presented previous adverse events with immunobiological drugs. One immunosuppressant was maintained and leflunomide added to the treatment. Patients were followed for six consecutive months. RESULTS: Leflunomide proved effective and safe in 12 (66.6%) out of the 18 patients. There was total control of cutaneous activity and prednisone was tapered from 17.5 to 6.0 mg/day (p<0.001). In addition, two of these patients that also had muscle involvement improved muscle strength after leflunomide treatment. Side effects or inefficacy were observed in six patients. There were no cases of serious infection or death. CONCLUSIONS: Leflunomide therapy appears to be effective and safe as an adjuvant drug in refractory DM with primarily cutaneous activity. Further studies are needed to confirm this data.

Does previous corticosteroid treatment affect the inflammatory infiltrate found in polymyositis muscle biopsies?

OBJECTIVES: The aim of the study was to evaluate the effect of the prior use of corticosteroids (CS) on the presence of inflammatory infiltrates (InI) in muscle biopsies of polymyositis (PM). METHODS: We retrospectively evaluated 60 muscle biopsy samples that had been obtained at the time of the diagnosis of PM. The patients were divided into three groups according to the degree of the InI present in the muscle biopsies: (a) minimal InI present only in an interstitial area of the muscle biopsy (endomysium, perimysium) or in a perivascular area; (B) moderate InI in one or two areas of the interstitium or of the perivascular area; and (C) moderate InI throughout the interstitium or intense inflammation in at least one area of the interstitium or of the perivascular area. RESULTS: The three groups were comparable regarding the demographic, clinical and laboratory features (p>0.05). Approximately half of the patients in each group were using CS at the time of the muscle biopsy. The median (interquartile) duration of CS use [4 (0-38), 4 (0-60) and 5 (0-60) days: groups A, B and C, respectively] and the median cumulative CS dose used [70 (0-1200), 300 (0-1470) and 300 (0-1800)mg] were similar between the groups (p>0.05). CONCLUSIONS: Previous CS use did not influence the presence or the degree of InI found in muscle biopsies in PM with clinical and laboratory disease activity. Our study showed that muscle biopsies should be performed this population, even in individuals who have already been taking CSs.

Reduction of ovarian reserve in adult patients with dermatomyositis.

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. METHODS: Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Müllerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. RESULTS: DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1±4.7 years, with disease duration of 5.6±3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of ≤1ng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. CONCLUSIONS: We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.

The high prevalence of metabolic syndrome in polymyositis.

OBJECTIVES: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that are associated with increased cardiovascular diseases (CVD). MetS has been systematically evaluated in all systemic autoimmune rheumatic diseases except for polymyositis (PM). This study aimed to evaluate the frequency of MetS in PM patients and analyse the possible association of MetS with traditional risk factors of CVD and PM-related clinical and laboratory features. METHODS: The present cross-sectional, single-centre study included 35 consecutive PM patients (Bohan and Peter, 1975) and 70 healthy controls. MetS diagnosis was determined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). RESULTS: The age, gender and ethnicity distributions between the PM and control groups were comparable (p>0.050). The median PM disease duration was 5 years. Compared with healthy subjects, PM patients had higher prevalence of MetS (45.7% vs. 20.0%, p=0.011). In an additional univariate analysis of PM patients with (n=26) and without (n=19) MetS revealed that patients with this complication were older (56.1±7.8 vs. 44.3±12.8 years; p=0.002) with more cumulative prednisolone doses, higher scores on the health assessment questionnaire and on the physician visual analogue scale (p<0.050). Disease duration was comparable between both groups (p>0.050). CONCLUSIONS: MetS and CVD risks are highly prevalent in PM. Monitoring for and early treatments of modifiable risk factors for CVD in PM patients are necessary.