Disease Activity In Dermatomyositis Research Articles

Belimumab ameliorates symptoms and disease activity in dermatomyositis and juvenile dermatomyositis patients refractory to standard therapy: a retrospective observational study

Belimumab ameliorates symptoms and disease activity in dermatomyositis and juvenile dermatomyositis patients refractory to standard therapy: a retrospective observational study

Association of Juvenile Dermatomyositis Disease Activity With the Expansion of Blood Memory B and T Cell Subsets Lacking Follicular Markers.

This study was undertaken to identify blood markers of juvenile dermatomyositis (DM) disease activity (DA), which are needed to improve disease management. The study comprised a total of 123 juvenile DM patients and 53 healthy controls. Results of laboratory tests (aldolase, creatinine kinase, lactate dehydrogenase [LDH], aspartate aminotransferase) and clinical measures of DA in patients with juvenile DM, including the Manual Muscle Testing in 8 muscles (MMT-8), Childhood Myositis Assessment Scale (CMAS), and disease activity scores (DAS) (total DAS for juvenile DM, the muscle DAS, and the skin DAS), were recorded when available. Surface phenotype of peripheral blood mononuclear cells was assessed using flow cytometry. Whole blood transcriptional profiles were studied using either RNA-sequencing or microarrays. Differential gene expression was determined using DESeq and compared by pathway and gene ontology analyses. Conventional memory (CD27+IgD-) B cells expressing low CXCR5 levels (CXCR5low/- CM B cells) were significantly increased in frequency and absolute numbers in 2 independent cohorts of juvenile DM patients compared with healthy controls. The frequency of CD4+ Th2 memory cells (CD45RA-CXCR5-CCR6-CXCR3-) was also increased in juvenile DM, especially in patients who were within <1 year from diagnosis. The frequency of CXCR5low/- CM B cells correlated with serum aldolase levels and with a blood interferon-stimulated gene transcriptional signature. Furthermore, both the frequency and absolute numbers of CXCR5low/- CM B cells correlated with clinical and laboratory measures of muscle DA (MMT-8, CMAS, aldolase, and LDH). These findings suggest that both CM B cells lacking the CXCR5 follicular marker and CXCR5- Th2 cells represent potential biomarkers of DA in juvenile DM and may contribute to its pathogenesis.

Low serum level of citrullinated histone H3 in patients with dermatomyositis.

We aimed at analyzing the serum levels of citrullinated histone H3 (CitH3) in patients with dermatomyositis (DM) and their association with disease activity. Serum CitH3 levels were measured using enzyme-linked immunosorbent assays in serum samples obtained from 93 DM patients and 56 healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of CitH3 and other disease variables. The association between CitH3 and disease variables was analyzed using Pearson's rank correlation. Serum CitH3 level was significantly lower in DM patients than in HCs (p < 0.001). The ROC curve analysis revealed that CitH3 strongly discriminated DM patients from HCs (area under the curve [AUC], 0.86), and a combination of CitH3 and the ratio of neutrophil to lymphocyte counts (NLR) showed a greater diagnostic value (AUC, 0.92). Serum CitH3 levels were markedly lower in DM patients with normal muscle enzyme levels than in HCs (all p < 0.001), and when compared to an elevated group, the CitH3 levels were comparable (all p > 0.05). The CitH3 levels showed no difference between DM in active and remission groups. However, in a paired test with 18 hospitalized DM patients, the CitH3 levels were higher in remission state than in active state. Moreover, the CitH3 levels showed no correlation with disease variables that were associated with the disease activity of DM. Serum CitH3 level may serve as a useful biochemical marker for screening patients with DM from HCs, while its role in monitoring DM disease activity requires further research.

Biomarkers of disease activity in dermatomyositis.

This review provides updates regarding biomarker studies that address key clinical unmet needs, which relate to the evaluation of the disease activity in patients with dermatomyositis. Increasing evidence supports that the serum levels of dermatomyositis-specific antibodies (DM-MSAs), which include anti-Mi-2, anti-NXP2, anti-MDA5, anti-TNF1-γ, and anti-SAE, are correlated with the disease activity. Moreover, serial measurements of DM-MSA levels may help to predict the disease status. Beyond the MSA, macrophage activation-related biomarker-soluble CD163, CD206, neopterin, and galectin-3/9 are the most currently talked biomarkers for disease activity in dermatomyositis; new circulating T-cell subsets CD4+CXCR5+CCR7loPD-1hi and TIGIT+CD226+ CD4 T cells can potentially harbor biomarkers of disease activity in dermatomyositis. In addition, LDGs and NETs were also shown to be correlated with the disease activities of dermatomyositis. Promising candidate biomarkers are now available for evaluating disease activity in dermatomyositis. These biomarkers need external validation in other large cohort studies.

Trichoscopic Signs in Dermatomyositis, Systemic Lupus Erythematosus, and Systemic Sclerosis: A Comparative Study of 150 Patients

Background: Hair and scalp involvement is prevalent in connective tissue diseases (CTDs). Trichoscopic features may provide a diagnostic implementation and enable differentiation among CTDs; however, a direct comparison of these signs among CTD patients is lacking. Objectives: To compare trichoscopic findings in dermatomyositis (DM), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) as well as determine their distinctive features and associations with disease activity. Methods: Trichoscopic photographs were taken from DM, SLE, and SSc patients and further evaluated for hair shaft and scalp surface abnormalities. Data regarding patients’ clinical manifestations, laboratory results, and disease activity were analyzed. Results: One hundred fifty participants, consisting of 30 DM, 60 SLE, and 60 SSc patients, were included. Perifollicular red-brown pigmentation, brown scattered pigmentation, and white patches were exclusive findings in DM, SLE, and SSc, respectively (p < 0.001). A multinomial logistic regression analysis revealed that DM demonstrated higher odds for having microaneurysmal blood vessels than SLE and SSc (odds ratio [OR] = 22.22, 95% confidence interval [CI] = 1.73–285.13, p = 0.017, and OR = 15.34, 95% CI = 1.36–177.59, p = 0.029, respectively). Polymorphic vessels forming a telangiectatic network suggested SSc over SLE (OR = 12.83, 95% CI = 1.35–121.98, p = 0.026), while avascular areas were more pronounced in SSc than DM and SLE (OR = 43.24, 95% CI = 5.17–361.67, p = 0.001, and OR = 0.03, 95% CI = 0.01–0.24, p = 0.001, respectively). In a quantile regression analysis, perifollicular red-brown pigmentation, reduction in hair diameter, and the absence of thin arborizing vessels were linked to higher disease activity in DM, SLE, and SSc, respectively (all p < 0.05). Conclusions: Trichoscopy is a valuable tool possessing diagnostic and prognostic values for CTDs. Specific trichoscopic features allow adequate distinction between DM, SLE, and SSc and may help identify active disease.

Hierarchical cluster analysis of cytokine profiles reveals a cutaneous vasculitis-associated subgroup in dermatomyositis.

Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles. Serum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM. Serum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM. Multiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10, IL-1RA, and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.

A phase 2, double-blinded, placebo-controlled trial of toll-like receptor 7/8/9 antagonist, IMO-8400, in dermatomyositis

To the Editor: Dermatomyositis (DM) is a rare inflammatory disease of muscle and skin. DM severity is thought to be driven, in part, by type I interferon signaling.1Huard C. Gullà S.V. Bennett D.V. Coyle A.J. Vleugels R.A. Greenberg S.A. Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis.Br J Dermatol. 2017; 176: 1224-1230Crossref PubMed Scopus (50) Google Scholar Because interferon is primarily induced by toll-like receptors (TLRs) 7/9, we hypothesized that antagonizing TLR7/9 could improve DM disease activity.2Baechler E.C. Bauer J.W. Slattery C.A. et al.An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity.Mol Med. 2007; 13: 59-68Crossref PubMed Scopus (196) Google Scholar,3Walsh R.J. Kong S.W. Yao Y. et al.Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis.Arthritis Rheum. 2007; 56: 3784-3792Crossref PubMed Scopus (205) Google Scholar We conducted a phase 2, multicenter, double-blind, randomized, placebo-controlled trial of IMO-8400, an oligonucleotide antagonist of TLR7/8/9, in DM.4Suárez-Fariñas M. Arbeit R. Jiang W. Ortenzio F.S. Sullivan T. Krueger J.G. Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.PLoS One. 2013; 8: e84634Crossref PubMed Scopus (80) Google Scholar,5Jiang W. Zhu F. Tang J. Kandimalla E. La Monica N. Agrawal S. IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in mouse models of psoriasis (119.8).J Immunol. 2012; 188: 119.8Google Scholar Thirty patients with Cutaneous Dermatomyositis Disease Area and Severity Index version 2 (CDASIv2) scores of 15 or greater were enrolled between November 2015 and June 2018. Patients were allowed to remain on stable prednisone (≤20 mg/d) and up to 1 immunomodulatory therapy from a prespecified list (Table I and Supplemental Table 1, A and B; available via Mendeley at https://doi.org/10.17632/f9vx46p3fc.1).Table IBaseline characteristics of the intent-to-treat populationCharacteristicsPlaceboIMO-84000.60 mg/kg1.8 mg/kgn11910Age, y, mean (SD)51.3 (10.6)48.3 (14.2)54.6 (14.1)Sex, n (%) Female7 (63.6)7 (77.8)9 (90.0) Male421Race, n (%) White11 (100)8 (88.9)9 (90.0) Black or African American01 (11.1)1 (10.0)CDASI, n (%) 15-201 (9.1)02 (20.0) ≥2110 (90.9)9 (100)8 (80.0)CDASI activity score, mean (SD)30.2 (9.8)33.0 (8.4)33.5 (14.7)Treatment-concomitant drugs, n (%) Systemic corticosteroids∗Methylprednisolone, prednisolone, and prednisone. (%)8 (72.7)5 (55.6)5 (50.0) DMARDs†Azathioprine, leflunomide, methotrexate, mycophenolate mofetil, and mycophenolic acid. (%)5 (45.5)6 (66.7)6 (60.0) Immunoglobulins (%)1 (9.1)01 (10.0)CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; DMARD, disease-modifying antirheumatic drugs; SD, standard deviation.∗ Methylprednisolone, prednisolone, and prednisone.† Azathioprine, leflunomide, methotrexate, mycophenolate mofetil, and mycophenolic acid. Open table in a new tab CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; DMARD, disease-modifying antirheumatic drugs; SD, standard deviation. Participants were stratified into 2 groups by CDASIv2 activity score (15-20 vs ≥21) and randomized 1:1:1 to receive weekly subcutaneous injections of IMO-8400 0.6 mg/kg, IMO-8400 1.8 mg/kg, or placebo for 24 weeks. Because IMO-8400 is associated with injection site reactions, the primary outcome used a modified CDASIv2 activity score (CDASI-a) excluding the injection site. Secondary assessments included the Manual Muscle Test 8 (MMT8). Participants were predominantly white (93.3%) and female (76.7%), with a median age of 54.5 years (Table I). The mean baseline CDASI-a was 32.1 and was generally equal across treatment arms (30.2 for placebo, 33.0 for 0.6 mg/kg, and 33.5 for 1.8 mg/kg). The most common injection site reactions were erythema, pain, and induration (Supplemental Tables II and III; available via Mendeley at https://doi.org/10.17632/f9vx46p3fc.1). Out of 30 patients, 11 discontinued the study—5 (16.7%) because of adverse events, 4 (13.3%) for lack of efficacy, and 2 (6.7%) because of withdrawal by the participant. CDASI-a improved for all groups over 24 weeks (−9.3 for 0.6 mg/kg, −8.8 for 1.8 mg/kg, and −7.3 for placebo) (Fig 1). There was no significant difference between placebo and treatment groups; the repeated-measures mixed model analysis of CDASI-a across visits of the combined IMO-8400 group compared to that of placebo showed a least squares mean difference of −1.9 (P = .238). The average changes in MMT8 between the end of trial and baseline were as follows: +3.8 for placebo, +1.8 for 0.6 mg/kg, and +2.8 for 1.8 mg/kg. Across visits, in comparison to the placebo, the least squares mean difference of MMT8 in the 0.6 mg/kg group and 1.8 mg/kg group was +0.4 (P = .846) and +2.3 (P = .250), respectively. IMO-8400 did not show clinical efficacy over placebo in treating DM skin or muscle disease. IMO-8400 may not have achieved high enough doses for the pharmacologic blockade of TLR7/9, or there may be roles for pathways outside of TLR7/9 in DM. Limitations of the study include the small sample size and patient use of concomitant medications. The authors would like to thank Dr Kristin Lynn Sainani and the members of the Sarin Lab for their critical review and feedback of the manuscript.

Response of dermatomyositis to the antimalarial quinacrine: A retrospective cohort study

To the Editor: Quinacrine (QC) is an antimalarial taken with hydroxychloroquine or chloroquine to treat dermatomyositis (DM).1,2 QC is prescribed at a constant dosage (100 mg/d), is well tolerated, and does not require blood or vision monitoring, but it may be associated with reversible skin yellowing.2-4 In 2019, the US Food and Drug Administration placed the manufacturer of QC on import alert.5 This is concerning because the lack of QC may increase reliance on steroids or immunosuppressants. To characterize the importance of the effects of QC on DM disease activity and quality of life, we present a retrospective study from a prospectively collected database of patients with DM.

P.08Interferon level assessed by ultrasensitive detection technology in myositis patients: a promising biomarker of disease activity in dermatomyositis and anti-synthetase syndrome

P.08Interferon level assessed by ultrasensitive detection technology in myositis patients: a promising biomarker of disease activity in dermatomyositis and anti-synthetase syndrome

Clinical value of a [18F]-FDG PET-CT muscle-to-muscle SUV ratio for the diagnosis of active dermatomyositis.

To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p < 0.001). SUVPROX/SUVMLT ratios in DM and their controls also differed significantly (p = 0.0012). The SUVPROX/SUVMLT ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%). A muscle-to-muscle SUVPROX/SUVMLT ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis. • [18F]-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM). • A ratio of SUV in proximal muscles (SUVPROX) to SUV in musculus longissimus thoracis (SUVMLT) could be used to determine active DM. • Active disease is suspected for SUV PROX /SUV MLT ratios greater than 1.73.

Galectin-9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation.

ObjectiveObjective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under‐ and overtreatment of patients. Recently, we identified 2 proteins, galectin‐9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin‐9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares.MethodsLevels of galectin‐9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross‐sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases.ResultsBoth cross‐sectionally and longitudinally, galectin‐9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve [AUC] 0.86–0.90 for galectin‐9 and CXCL10; AUC 0.66–0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin‐9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin‐9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin‐9 and P < 0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin‐9 and P < 0.0001 for CXCL10).ConclusionIn this study, galectin‐9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies.

Pro-inflammatory S100A11 is elevated in inflammatory myopathies and reflects disease activity and extramuscular manifestations in myositis

BackgroundS100A11 (calgizzarin), a member of the S100 family, is associated with oncogenesis, inflammation and myocardial damage. Our aim was to analyse S100A11 in idiopathic inflammatory myopathies (IIMs) and its association with disease activity features and cancer development. MethodsS100A11 in muscle was determined by immunohistochemistry in polymyositis (PM), dermatomyositis (DM), myasthenia gravis (MG) and in subjects without autoimmune inflammatory disease (HC). S100A11 in plasma was measured in 110 patients with IIMs (PM, DM, and cancer associated myositis (CAM) patients) and in 42 HC. Disease activity was assessed by myositis disease activity assessment (MYOACT), muscle enzymes and C-reactive protein (CRP) were measured by routine laboratory techniques; autoantibodies by immunoprecipitation or by immunoblot. ResultsWe observed an accumulation of S100A11 in the cytoplasm of regenerating and necrotizing muscle fibres of PM and DM patients. S100A11 was increased in plasma of all myositis patients compared to HC (3.8 (1.5–16.8) vs 2.8 (1.7–11.2) ng/ml, p = 0.011) and in DM and CAM patients compared to HC (4.0 (2.2–14.9) and 4.5 (1.5–9.1) vs 2.8 (1.7–11.2) ng/ml, p < 0.001 and p = 0.022, respectively). In all myositis patients, S100A11 correlated with the levels of lactate dehydrogenase (r = 0.256, p = 0.011), aspartate aminotransferase (AST) (r = 0.312, p = 0.002), CRP (r = 0.254, p = 0.022) and MYOACT (r = 0.245, p = 0.022). S100A11 was associated with MYOACT (r = 0.377, p = 0.030) and pulmonary and cutaneous disease activity in DM patients (r = 0.408, p = 0.017 and r = 0.417, p = 0.01, respectively). S100A11 was related to the levels of AST (r = 0.412, p = 0.027) in PM and to the levels of creatine phosphokinase (r = 0.432, p = 0.028) in CAM patients. ConclusionsWe show for a first time a potential implication of S100A11 in the local inflammatory and tissue remodelling processes in myositis and an association of circulating S100A11 with disease activity and extra muscular manifestations in DM.

Peripheral blood lymphocyte subset repertoires are biased and reflect clinical features in patients with dermatomyositis

Objective: Dermatomyositis (DM) is an idiopathic inflammatory myopathy which often involves the lungs. DM is likely to be associated with aberrant T- and B-cell activation in the pathogenesis because of the proven effectiveness of T- and B-cell-targeted treatments. Assuming that the aberrant activation is reflected by biases in the lymphocyte subset repertoires, we aimed to elucidate these biases, especially in relation to clinical features of DM.Method: Based on the immunophenotyping standardized by the Human Immunology Project Consortium, untreated 13 DM patients, including seven patients with interstitial lung disease (ILD), and 18 age-matched healthy donors (HDs) were examined for proportions of peripheral blood lymphocyte subsets. Six DM patients were examined before and after successful induction of remission.Results: Naïve CD4+ T cells and naïve B cells were more abundant, while there were fewer naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, Th1 cells, Tfh cells, and memory B cells in DM patients than in HDs. When the patients were subgrouped according to the presence of ILD, the lymphocyte subset repertoires in the patients with ILD contributed to the statistical differences in all the biased lymphocyte subset proportions. After treatment, transitional B cells vanished and there was an increase in memory B cells.Conclusion: The lymphocyte subset repertoires in the DM patients were biased, and were associated with the presence of ILD and disease activity of DM.

Serum Interleukin-18 Level is Associated With Disease Activity and Interstitial Lung Disease in Patients With Dermatomyositis.

This study aims to demonstrate the utilization of serum interleukin-18 (IL-18) level as a biomarker for disease activity and organ damage in patients with dermatomyositis (DM) or polymyositis (PM) using the Myositis Disease Activity Assessment Tool. Forty-nine patients (13 males, 36 females) with idiopathic inflammatory myopathies were enrolled in the study. Patients were diagnosed with DM (n=33) or PM (n=16). Twenty age- and sex-matched healthy volunteers (9 males, 11 females) who were determined to be free of autoimmune disease were included as a control group. Disease activity and organ damage were assessed with Myositis Disease Activity Assessment Tool. Serum IL-18 level was measured with enzyme-linked immunosorbent assay and the differences between patient groups were determined. The mean ages of DM or PM patients were 44 and 45, respectively. Interstitial lung disease (ILD) was found in 24 patients (48.98%), including 18 patients with DM (54.55%) and six patients with PM (37.5%). There was no significant difference of disease duration between DM patients (17.5±22.3 months) and PM patients (14.9±28.7 months). Serum IL-18 level in DM (669.2±528.1 pg/mL) was significantly higher than that in the control group (388.3±139.4 pg/mL, p=0.017), but no significant difference was observed between the PM and control group. IL-18 was significantly higher in DM patients with ILD (890.5±618.8 pg/mL) than in patients without ILD (403.8±84.8 pg/mL, p=0.003). It was significantly elevated in patients with severe disease activity (1001.71±694.2 pg/mL) than in those with moderate (485.3±102.2 pg/mL) or mild disease activity (421.0±270.2 pg/mL) (p=0.039). In DM patients, IL-18 was significantly correlated with global disease activity and disease activity in the skin, lung, and heart. Serum IL-18 level was higher in patients with DM and this was associated with disease activity and ILD complication. Thus, it can be used as a valuable serological marker for DM disease activity and ILD complication.

Red blood cell distribution width and neutrophil to lymphocyte ratio are correlated with disease activity of dermatomyositis and polymyositis

Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR. Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model. PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT. Both RDW and NLR are useful indices in assessing the disease activity of PM/DM.

Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis.

Dermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle. The purpose of this study was to determine whether an association exists between clinical skin disease activity as measured by the validated Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and type 1 interferon (IFN) pathway biomarkers in the blood of patients with DM. Forty-two patients with DM and 25 healthy volunteers were prospectively enrolled. CDASI scores were obtained, and serum and blood RNA were isolated from all participants. Associations between CDASI activity and type 1 IFN-inducible gene signature were assessed cross-sectionally in all patient samples and longitudinally on 13 paired visits via transcriptional profiling analyses. By RNAseq analysis, type 1 IFN-inducible genes were the most highly differentially regulated. A CDASI activity threshold of 12 was correlated with an elevated type 1 IFN gene signature and with serum IFN-β, but not with IFN-α protein. Expression analysis showed that all patients with mild disease activity had a low type 1 IFN gene signature, while 93% of patients with moderate-to-high disease activity had elevated gene signature. In longitudinal analysis, changes in CDASI activity showed nonsignificant trends with concordant directional changes in gene signature. A type 1 IFN pathway signature biomarker in blood is highly correlated with CDASI activity scores in DM, and may be a promising surrogate clinical trial end point. The correlation of serum IFN-β, but not IFN-α, with both a gene signature and CDASI suggests that IFN-β drives disease activity in DM.

Design Considerations for Clinical Trials Using the Cutaneous Dermatomyositis Disease Area and Severity Index as a Primary Endpoint

Objective: Skin inflammation is a universal characteristic of the multisystem inflammatory myopathy dermatomyositis (DM). About 35% of DM patients have a polycyclic or chronic disease course, usually due to active skin disease, despite standard of care therapy, demonstrating a significant unmet need for novel treatment options. To test the efficacy of novel therapeutics, feasible prospective clinical trials must be designed that employ quantitative endpoints. The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) is a validated, reliable, and responsive measurement of cutaneous DM disease activity and damage. The primary objectives were to identify requisite design parameters (e.g., target trial population, duration, frequency of assessments, treatment difference, sample size) for a proofofconcept clinical trial of a novel therapy in patients with DM. Methods: Trial simulations were conducted to determine sample size and statistical power. Simulation inputs were obtained from analyses of CDASI natural history data obtained from 115 adult DM patients followed at Stanford University. Results: A population with baseline CDASI Activity scores ≥ 15 was simulated to eliminate a potential floor effect in patients with milder disease and to mimic a clinical trial population with moderate to severe skin disease. Given a 24 weeks trial with monthly disease assessments, simulations demonstrated that 45 patients per group were required to detect a 5 point treatment difference and 12 patients per group were required to detect a 10 point treatment difference with 80% statistical power using a 2 sided test. Conclusion: This study provides evidence that the CDASI is a practical and feasible primary efficacy endpoint for DM clinical trials and lays out a framework for a clinical trial using CDASI as a primary endpoint.

Immunological biomarkers in dermatomyositis.

Dermatomyositis (DM) is a chronic acquired disorder that affects primarily the muscle and skin. The pathogenesis of DM, as well as methods for monitoring disease activity and predicting response to therapy, are subjects of active research. Studies looking to unveil the pathogenesis of DM have revealed key molecules that are potential biomarkers of disease activity. This article reviews briefly the recently discovered molecules that are candidate immunological biomarkers for diagnosing and monitoring disease activity in DM.

Improvement in the cutaneous disease activity of patients with dermatomyositis is associated with a better quality of life.

Cutaneous dermatomyositis (DM) disease activity is associated with decreased quality of life. To assess if an improvement in quality of life, as measured by the Skindex-29 and patient-reported itch and pain on a 10-point visual analogue scale (VAS), correlated with an improvement in cutaneous DM disease activity. Patients with a completed cutaneous DM disease area and severity index [Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)] at two visits separated by at least 2months were classified into responder (n=15) and nonresponder (n=30) groups according to the point change in the CDASI activity scores between visits. Responders had at least a four-point improvement in CDASI activity, indicating clinically relevant improvement. The change from baseline to the follow-up visit of the Skindex-29 subscale scores for the responders vs. the nonresponders were significantly different for emotions (P<0·01), functioning (P<0·01) and symptoms (P<0·01). The change in VAS score between responders and nonresponders was also significant for itch (P=0·01) and pain (P=0·04). There was no significant difference between the groups in terms of disease subtype, sex, race, age, treatment for DM, smoking history or a history of malignancy within 5years of a diagnosis of DM. This is the first study to demonstrate that the quality of life of patients with DM improved as their cutaneous disease activity decreased.

Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course

Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immunomodulating agents, we prospectively evaluated whether interferon (IFN)-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. Peripheral blood and clinical data were collected from 51 patients with juvenile or adult DM prospectively over 2 study visits. We performed disease activity measurements and calculated whole-blood type I IFN gene and chemokine scores. We also measured serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6). Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before adjustment for medication use (r = 0.33, P = 0.023) and with changes in the IFN chemokine score before and after adjustment for medication use (r = 0.53, P < 0.001 and r = 0.50, P < 0.001, respectively). Changes in muscle and extramuscular visual analog scale (VAS) scores correlated positively with changes in IFN gene and chemokine scores (P = 0.002, P < 0.001, P = 0.095, P < 0.001). Serum levels of IL-6, IL-8, and tumor necrosis factor α (TNFα) correlated positively with changes in global, muscle, and extramuscular VAS scores (P < 0.05). Our findings suggest that changes in type I IFN gene and chemokine scores as well as in levels of IL-6, IL-8, and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunomodulating agents.