Myositis Disease Activity Assessment Research Articles

Soluble IL-2 Receptor in Dermatomyositis: Its Associations with Skin Ulcers and Disease Activity.

Objective To investigate the role of soluble interleukin-2R (sIL-2R) in idiopathic inflammatory myopathies (IIM). Methods Serum sIL-2R levels were measured in 74 dermatomyositis (DM), 16 immune-mediated necrotizing myopathy (IMNM), 24 rheumatoid arthritis (RA), 20 systemic lupus erythematosus (SLE), and 20 healthy controls (HCs) by chemiluminescent immunometric assay. Clinical features and laboratory data were collected from electronic medical record. Disease activity was evaluated by using physician global disease activity and myositis disease activity assessment visual analog scale (MYOACT) on admission. 20 DM patients were followed. Serum sIL-2R levels were analyzed and compared with clinical features, laboratory data, and measures of disease activity. Results Serum sIL-2R levels were significantly higher in DM patients than in IMNM patients and HCs (648.8 ± 433.1 U/ml vs. 352.3 ± 126.0 U/ml and 648.8 ± 433.1 U/ml vs. 285.8 ± 101.9 U/ml, respectively; all P < 0.001), while there was no significant difference between IMNM and HCs. There were also no significant differences of sIL-2R levels in DM, SLE, and RA. Importantly, serum sIL-2R levels were significantly higher in treatment-naïve or active DM patients than those that are not (1100.9 ± 550.4 U/ml vs. 615.6 ± 330.4 U/ml, P = 0.006; 808.8 ± 421.6 U/ml vs. 339.8 ± 103.4 U/ml, P < 0.001). DM patients with skin ulcers had significantly higher sIL-2R levels than those without (889.3 ± 509.9 U/ml vs. 640.0 ± 368.7 U/ml, P = 0.023). Cross-sectional analysis in DM showed that sIL-2R levels positively correlated with CK, ESR, CRP, ferritin, physician VAS, and MYOACT scores (rho = 0.278, rho = 0.474, rho = 0.469, rho = 0.454, r = 0.646, and r = 0.600, respectively; all P < 0.05), negatively correlated with T cell counts and MMT8 scores (r = −0.380, P = 0.002; rho = −0.394, P = 0.001). Follow-up study showed that changes in sIL-2R levels after treatment correlated with changes in physician VAS and MYOACT scores (r = 0.823 and r = 0.695, respectively; all P < 0.01). Conclusion Serum sIL-2R levels were elevated in DM but not in IMNM. Serum sIL-2R could act as a disease activity marker and be associated with ulcerative skin lesions in DM.

Myositis-specific autoantibodies in adults with idiopathic inflammatory myopathy: correlations with diagnosis and disease activity.

To determine the relationship of myositis autoantibodies with the diagnosis and severity of idiopathic inflammatory myopathy (IIM) using the 2017 EULAR/ACR idiopathic inflammatory myopathy classification criteria and the myositis disease activity assessment tool (MDAAT). Patients who met the new diagnostic criteria were tested for serum myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), and then classified into different subgroups based on autoantibody positivity. Patients were also diagnosed with possible IIM, probable IIM, and definite IIM. The MDAAT was used to evaluate muscular and extramuscular disease activity. The relationships of diagnostic classification with positivity for different myositis autoantibodies were determined. There were 118 patients, and 81% of them had one or more myositis autoantibody. Anti-Jo-1 was the most common MSA, and anti-Ro-52 was the most common MAA. Sixteen patients (14%) had possible IIM, 36 (31%) had probable IIM, and 66 (56%) had definite IIM. MSA-positive patients were significantly more common in the definite IIM group, but MAA positivity was unrelated to diagnostic classification. Positivity for MSAs or MAAs had no correlations with muscle disease activity. Extramuscular disease activity was greater in MSA-positive than MSA-negative patients, but MAA positivity had no significant association with extramuscular disease activity. MSA positivity aids in the diagnosis of IIM. MSA positivity was associated with greater extramuscular disease activity. Improving the clinical application of MSAs may enhance the individualized treatment of patients with IMM. Key Points • In this paper, we explore the relationships between the myositis autoantibodies and the diagnosis and the disease activity of inflammatory myopathy. • Positive myositis-specific autoantibodies is associated with the establishment of diagnosis and higher extramuscular disease activity. • Thus, more extensive application of myositis autoantibodies maybe the key for further disease assessment and research.

Aberrant expansion of circulating CD4+ CXCR5+ CCR7lo PD1hi Tfh precursor cells in idiopathic inflammatory myopathy.

To determine circulating follicular T helper (Tfh) cell precursor and its relationship with clinical characteristics in idiopathic inflammatory myopathy (IIM). The study population included 47 patients with IIM and 30 healthy controls. Circulating CD4+ CXCR5+ CCR7lo PD-1hi T cells and intracellular interleukin (IL)-21 were assessed by flow cytometry. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay. The disease activity was evaluated using myositis disease activity assessment visual analog scales (VAS) as well as muscle and physician global assessment (PGA). The percentage of the CCR7lo PD-1hi subset cells within CD4+ CXCR5+ T cells was significantly increased in patients with IIM compared to that in healthy controls (14.3±6.5 vs 11.4±2.6, P=.009). Patients with higher percentages of CCR7lo PD-1hi subsets presented with higher PGA VAS (P=.000), muscle VAS (P=.000), as well as serum creatinine kinase (CK) levels (P=.000) than those with lower percentages of CCR7lo PD-1hi subsets. IL-21 expression significantly increased in CD4+ CXCR5+ CCR7lo PD-1hi T cells in patients with IIM compared to that in healthy controls (26.07±7.38 vs 19.25±5.67, P=.001). Meanwhile, both the CCR7lo PD-1hi subset and intracellular IL-21 expression in IIM patients showed significantly positive correlation with PGA VAS, muscle VAS and serum CK levels. Circulating CD4+ CXCR5+ CCR7lo PD-1hi T cells and intracellular IL-21 decreased significantly when disease was improved (P=.018; P=.028). The percentage of circulating CCR7lo PD-1hi subset among total CD4+ CXCR5+ T cells and intracellular IL-21 expression expanded and showed significant correlation with disease activity in IIM. The circulating follicular helper T cell precursor may be involved in the pathogenesis, especially muscle injury in IIM.

Correlation of PMN elastase and PMN elastase-to-neutrophil ratio with disease activity in patients with myositis

BackgroundPolymorphonuclear (PMN) elastase plays an important role in a variety of inflammatory disorders. Our aim was to analyse PMN elastase in idiopathic inflammatory myopathies (IIMs) and its association with disease activity.MethodsPMN elastase levels were measured using enzyme-linked immunosorbent assay in serum samples obtained from 74 patients with myositis (58 with dermatomyositis [DM] and 16 with polymyositis [PM]) and 22 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of PMN elastase level and PMN elastase-to-neutrophil ratio (ENR) in patients with active and remission myositis. The association of serum PMN elastase level and ENR with disease variables was evaluated in patients with IIMs. The disease specificity of PMN elastase level and ENR was further examined in 60 patients with other systemic autoimmune diseases.ResultsPMN elastase level and ENR were significantly higher in patients with active IIMs, DM, and PM than in patients with remission. ROC curve analysis revealed that PMN elastase level and ENR both outperformed creatine kinase (CK), the currently used laboratory marker, and strongly discriminated patients with active disease and those with remission of IIMs, DM, and PM (area under the ROC curve [AUC] 0.9, 0.9, and 0.88 for PMN elastase; AUC 0.96, 0.96, and 1.0 for ENR; AUC 0.72, 0.70, and 0.80 for CK, respectively). PMN elastase level and ENR were positively correlated with myositis disease activity assessment, CK, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and erythrocyte sedimentation rate. PMN elastase level and ENR were higher in the anti-PM-Scl positive myositis group than those in the anti-PM-Scl negative myositis group. Nevertheless, PMN elastase was not a specific disease marker for IIMs when compared with other autoimmune diseases.ConclusionsPMN elastase, particularly ENR, were significantly correlated with disease activity and could serve as useful biochemical markers for evaluating the disease activity of patients with IIMs. Thus, they are potentially helpful in monitoring disease progression and guiding treatment.

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.

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features. 11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry. TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls. The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

A patient with dysphagia and muscle weakness

BACKGROUND: There are five major types of inflammatory myopathies (IM), including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, antisynthetase syndromes, and inclusion body myositis. Grouped together, the incidence of IM is >4 cases/100,000 with a prevalence of 14-32/100,000. Type-specific IM diagnoses are based on the pattern of muscle weakness and the results of electromyographs, MRIs, muscle biopsies, and measurements of myositis-specific autoantibodies1. We report the case of an elderly man with an inflammatory myopathy whose presenting complaint was dysphagia. OBJECTIVE: To review the clinical and laboratory manifestations of inflammatory myopathy-associated dysphagia. CASE REPORT: The patient is an 81-year-old retired Navy aviator who presented with a chief complaint of difficulty in swallowing both solids and liquids of several months duration. The dysphagia was associated with bouts of coughing, the expectoration of white foamy sputum, increased production of saliva, a weight loss of 5 kg, generalized myalgias, and worsening fatigue and weakness. The patient had a past medical history of essential hypertension, hyperlipidemia, autoimmune thyroiditis, V617F JAK2 + essential thrombocytosis, white matter microangiopathy, and a small lacunar infarction of the right caudate nucleus. There was no family history of autoimmune disease. On neurological examination, testing of cranial nerves II-XII and sensation to light touch, pin, temperature, and vibration was normal. The shoulder and upper arm strength was diminished bilaterally without evident muscle tenderness, atrophy or fasciculations. The patient could not rise from the supine position without assistance nor keep his arms elevated above his head without fatiguing. The strength in his lower extremities was normal. Deep tendon reflexes were normal and plantar responses were flexor. He had a single Gottron’s nodule and a faint erythematous rash involving his scalp, back and forearms. His Myositis Disease Activity Assessment (MDAAT) is shown in Table 1. Table 1. Myositis Disease Activity Assessment Tool (MDAAT) Findings on laboratory assessment included a normochromic normocytic anemia, thrombocyth-emia, a positive FANA IgG titer of 1:1280, and elevated levels of creatinine phosphokinase (1,373 U/L), aldolase (25.8 U/L), and antibodies to Mi-2 alpha, Mi-2 beta, MDA-5 and NXP-2 antigens. Anti-doubled stranded DNA, anti-RNP, anti-SM, anti-Jo-1, anti-SRP, anti-TIF-1ƴ and anti-synthetase antibody titers were negative. A modified barium swallow revealed severe oropharyngeal dysfunction with aspiration. An electromyograph, a muscle biopsy, and a MRI of cervical spinal muscles were indicative of an inflammatory myopathy. DISCUSSION: Dysphagia as a result of weakness of the oropharyngeal, laryngeal and esophageal musculature has been reported to develop in 10% to 73% of patients with inflammatory myopathy (IM) at some time during the course of their disease, and is most frequently seen in those with inclusion body myositis or malignancy- associated dermatomyositis. In a Mayo Clinic review of 62 patients with IM-associated dysphagia, 42% had inclusion body myositis, 29% dermatomyositis, 15% polymyosi-tis, and 15% an overlap syndrome. Dysphagia as the presenting complaint was most common in patients with inclusion body myositis (42%) followed by polymyositis and the overlap syndrome (11% each). IM-associated dysphagia had a mortality rate of 31% – 64% with the highest incidence of death occurring in patients with percutaneous endoscopic gastrostomies, an indirect measure of the severity of dysphagia. Death was most commonly the result of recurrent aspiration2. In a study of 92 patients with adult-onset dermatomyositis, Mugii and associates found that dysphagia was most prevalent in elderly patients, in males, and in patients with internal malignancies and/or elevated anti-TIF-1ƴ antibody levels3. In keeping with this report, the presented case is an elderly man with clinical and immunological evidence supporting a diagnosis of dermatomyositis, including an erythematous rash, a Gottron’s sign, and anti-Mi-2, anti-MDA-5, and anti-NXP-2 antibodies – autoantibodies associated with myositis, a classic dermatomyositis rash, and possible malignancy (see Table 2). Table 2. Patient’s myositis-specific autoantibodies* Agents most commonly used and reported to be beneficial in treating IM-associated dysphagia include prednisone, azathioprine, methotrexate, intravenous immunoglobulin, hydroxychloroqui-ne, and mycophenolate mofetil. Interventional procedures include enteral feeding and cricopharyngeal myotomies and dilations2. Inclusion body myositis is often recalcitrant to immunosuppressive treatment and is more likely to require interventional measures4. Our patient’s dysphagia is improving on methotrex-ate and prednisone. It is important to note that myositis patients presenting with complaints of dysphagia and weakness may be misdiagnosed as having amyotrophic lateral sclerosis, a disease in which serum CPK levels may be elevated and bulbar onset is common.

Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis

BackgroundB-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity.MethodsSerum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 anti-Jo-1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3–5 time points (23 cases) were included. Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM).ResultsCross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels. PA revealed direct effects of anti-Jo-1 antibodies on CK (β = 0.41) and both direct (β = 0.42) and indirect (through anti-Jo-1 antibodies; β = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Δ) were associated with Δmyoglobin and Δaminotransferases and changes of BAFF correlated with ΔCK, Δcutaneous, Δmuscle, Δglobal, and Δskeletal disease activities.The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%). The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities.ConclusionOur findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.

Elevated serum YKL-40 correlates with clinical characteristics in patients with polymyositis or dermatomyositis.

Serum YKL-40 has been proved to be a promising biomarker for estimating the disease activity of several autoimmune diseases. However, its utility in polymyositis or dermatomyositis has not been established. The aim of this study was to investigate the utility of YKL-40 in patients with polymyositis/dermatomyositis. Patients with definite polymyositis/dermatomyositis who visited the Second People's Hospital of Wuxi between April 2016 and March 2017 were prospectively enrolled. Eighty-seven healthy individuals were set as a control. Serum YKL-40 of all participants was determined using ELISA. The associations between YKL-40 and clinical characteristics of polymyositis/dermatomyositis were analysed using the Student's t-test, Mann-Whitney test and receiver operating characteristic curve analysis. A total of 99 patients with polymyositis/dermatomyositis were enrolled. The patients with polymyositis/dermatomyositis had significantly higher serum YKL-40 concentration. Patients with interstitial lung disease had significantly higher YKL-40 concentration than those without. Serum YKL-40 was positively correlated with myositis disease activity assessment visual analogue scale, C-reactive protein, erythrocyte sedimentation rate and ferritin. The area under receiver operating characteristic curve of YKL-40 for identifying interstitial lung disease was 0.82. Serum YKL-40 is a useful biomarker for estimating disease activity or severity of polymyositis/dermatomyositis.

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.

Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab.

The aim was to assess the efficacy of rituximab for the cutaneous manifestations of adult DM and JDM. Patients with refractory adult DM (n = 72) and JDM (n = 48) were treated with rituximab in a randomized placebo-phase-controlled trial [either rituximab early drug (week 0/1) or rituximab late arms (week 8/9), such that all subjects received study drug]. Stable concomitant therapy was allowed. Cutaneous disease activity was assessed using the Myositis Disease Activity Assessment Tool, which grades cutaneous disease activity on a visual analog scale. A myositis damage assessment tool, termed the Myositis Damage Index, was used to assess cutaneous damage. Improvement post-rituximab was evaluated in individual rashes as well as in cutaneous disease activity and damage scores. The χ2 test, Student's paired t-test and Wilcoxon test were used for analysis. There were significant improvements in cutaneous disease activity from baseline to the end of the trial after rituximab administration in both adult DM and JDM subsets. The cutaneous visual analog scale activity improved in adult DM (3.22-1.72, P = 0.0002) and JDM (3.26-1.56, P <0.0001), with erythroderma, erythematous rashes without secondary changes of ulceration or necrosis, heliotrope, Gottron sign and papules improving most significantly. Adult DM subjects receiving rituximab earlier in the trial demonstrated a trend for faster cutaneous response (20% relative improvement from baseline) compared with those receiving B cell depletion later (P = 0.052). Refractory skin rashes in adult DM and JDM showed improvement after the addition of rituximab to the standard therapy in a clinical trial.

Clinical Characteristics of Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Antibodies in Chinese Patients with Idiopathic Inflammatory Myopathies.

ObjectiveThe objective of this study was to detect the prevalence of anti-3-hydroxyl-3- methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies in Chinese patients with idiopathic inflammatory myopathies (IIMs), and to analyze the clinical features of the antibody-positive IIM patients.MethodsThe presence of anti-HMGCR antibodies was detected in 405 patients with IIMs, 90 healthy controls, and 221 patients with other rheumatic diseases by using an ELISA kit. Clinical data from anti-HMGCR antibody-positive and -negative patients were compared. Long-term follow-up of the anti-HMGCR antibody-positive patients was conducted to evaluate the role of anti-HMGCR antibody in IIM disease prognosis.ResultsOf the 405 IIM patients, 22 (5.4%) were found to carry the anti-HMGCR antibody. These IIM patients were predominantly female (73%), and only 3 anti-HMGCR antibody-positive patients with IIM were exposure to statins. Most patients experienced progressive onset, and presented with muscular weakness. Dysphagia was observed in half of the patients (p < 0.01), and 15% of these patients experienced the complication of interstitial lung disease (ILD) (p > 0.05). Mean creatine kinase (CK) levels were higher in antibody-positive patients than in antibody-negative patients (p < 0.05). Muscle biopsies were available from 12 anti-HMGCR antibody-positive patients, eight who experienced myofiber necrosis and showed very little or no evidence of inflammatory cell infiltrates in their muscle biopsies. Of these eleven patients who were followed-up 2.5- to 29-month, 73% experienced improvement after treatment. A cross-sectional study showed that anti-HMGCR antibody levels were significantly associated with CK levels (r = 0.486, p = 0.026) as well as with Myositis Disease Activity Assessment (MYOACT) scores (r = -0.67, p = 0.003) during the initial visit. However, changes in serum anti-HMGCR antibody levels did not correlate with changes in CK levels, Manual Muscle Testing 8 (MMT-8) scores or MYOACT scores in long-term follow-up.ConclusionThe major clinical features of anti-HMGCR antibody-positive Chinese IIM patients were muscle weakness and dysphagia, which were seen in patients with and without statin exposure. This subtype of patients were responsive to immunosuppressive treatment and received good prognoses after treatment, but serum levels of the anti-HMGCR antibody do not correlate with disease activity.

Magnetic resonance measurement of muscle T2, fat-corrected T2 and fat fraction in the assessment of idiopathic inflammatory myopathies.

This study examines the utility of MRI, including T2 maps and T2 maps corrected for muscle fat content, in evaluating patients with idiopathic inflammatory myopathy. A total of 44 patients with idiopathic inflammatory myopathy, 18 of whom were evaluated after treatment with rituximab, underwent MRI of the thighs and detailed clinical assessment. T2, fat fraction (FF) and fat corrected T2 (fc-T2) maps were generated from standardized MRI scans, and compared with semi-quantitative scoring of short tau inversion recovery (STIR) and T1-weighted sequences, as well as various myositis disease metrics, including the Physician Global Activity, the modified Childhood Myositis Assessment Scale and the muscle domain of the Myositis Disease Activity Assessment Tool-muscle (MDAAT-muscle). Mean T2 and mean fc-T2 correlated similarly with STIR scores (Spearman rs = 0.64 and 0.64, P < 0.01), while mean FF correlated with T1 damage scores (rs = 0.69, P < 0.001). Baseline T2, fc-T2 and STIR scores correlated significantly with the Physician Global Activity, modified Childhood Myositis Assessment Scale and MDAAT-muscle (rs range = 0.41-0.74, P < 0.01). The response of MRI measures to rituximab was variable, and did not significantly agree with a standardized clinical definition of improvement. Standardized response means for the MRI measures were similar. Muscle T2, fc-T2 and FF measurements exhibit content validity with reference to semi-quantitative scoring of STIR and T1 MRI, and also exhibit construct validity with reference to several myositis activity and damage measures. T2 was as responsive as fc-T2 and STIR scoring, although progression of muscle damage was negligible during the study.

Magnetic resonance imaging changes of thigh muscles in myopathy with antibodies to signal recognition particle.

The aim of this study was to evaluate muscle MRI changes and the role of MRI in monitoring therapy in patients with myopathy associated with antibodies to signal recognition particle (anti-SRP myopathy). We identified 12 patients with anti-SRP myopathy [6 females and 6 males; mean age of onset 38.5 years (s.d. 12.4), mean duration 22.8 months (s.d. 20.6). The main symptoms were proximal limb muscle weakness. Mean serum creatine kinase levels were moderately increased. Muscle biopsies revealed necrotizing myopathy in all patients, with obvious connective tissue proliferation in five patients and a single focus of lymphocytic infiltration in the endomysium in one. The myositis disease activity assessment (MYOACT) visual analogue scales scores were assessed. Muscle MRI was performed through the thighs. All patients were treated with corticosteroids and other immunosuppressive drugs. MRI revealed fatty infiltration and oedema in the thigh muscles of all 12 patients. Prominent fatty infiltration was present in 4 of the 12 patients. The hamstrings and adductor magnus were the most severely infiltrated and the quadriceps femoris the least. Obvious oedema was observed in 10 of the 12 patients, the most severely affected muscles being the vastus lateralis, rectus femoris, biceps femoris and adductor magnus, with relative sparing of the vastus intermedius. The degree of oedema was not correlated with creatine kinase levels or MYOACT scores. The four patients with striking fatty infiltration were refractory to therapy. MRI of the thigh muscles shows a distinct pattern of oedema and fatty infiltration and can be used to monitor the treatment of patients with anti-SRP myopathy.

The metastasis promoting protein S100A4 levels associate with disease activity rather than cancer development in patients with idiopathic inflammatory myopathies.

IntroductionThe aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis.MethodsSerum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated.ResultsAll myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (β = 0.552; P = 0.002) in PM patients and with MYOACT (β = 0.557; P = 0.003) and CRP levels (β = 0.391; P = 0.029) in DM patients.ConclusionsCirculating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0468-2) contains supplementary material, which is available to authorized users.

OP0236 Elevated Soluble CD163 Levels as A Marker of Macrophage Activation in Polymyositis and Dermatomyosits: Associated with Macrophage Infiltration in Muscle Tissue

BackgroundCD163 is a monocyte/macrophage-restricted transmembrane glycoprotein and shedding of membrane CD163 through a proteolytic process produces soluble CD163 molecule (sCD163). The concentration of sCD163 in plasma may be a marker...

Prevalence and associated factors of reduced bone mineral density in patients with idiopathic inflammatory myopathies

To determine the prevalence and identify the associated factors of reduced bone mineral density (BMD) in patients with idiopathic inflammatory myopathies (IIMs). Existing patients diagnosed to have IIMs were recruited for measurement of BMD by dual energy X-ray absorptiometry. Demographic, clinical and treatment variables of these patients were recorded. The prevalence of osteopenia and osteoporosis were calculated. Using multivariate analysis, the independent associated factors for reduced BMD were evaluated. Thirty-eight patients with IIMs completed the study with 32 (84.2%) being female. The mean age of the patients was 52.8±13.0years. Nine (23.7%) patients had osteoporosis and 18 (47.4%) had osteopenia. Multivariate analysis revealed female gender and low serum albumin levels at onset were associated with lower spinal BMD. For femoral neck, the factors associated with lower BMD were high Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT) score and high cumulative prednisolone dose. Reduced BMD is prevalent in patients with IIMs. Female gender, low serum albumin level at onset, high disease activity and high cumulative corticosteroid dose appeared to be the independent associated factors. Regular assessment of BMD is advisable. The use of anti-osteoporotic and steroid-sparing agents should be encouraged.

Disease activity and prognostic factors in juvenile dermatomyositis: a long-term follow-up study applying the Paediatric Rheumatology International Trials Organization criteria for inactive disease and the myositis disease activity assessment tool

The aims of this study were to examine disease activity by the Paediatric Rheumatology International Trials Organization (PRINTO) criteria for inactive disease and the Myositis Disease Activity Assessment Tool (MDAAT) in JDM patients after long-term follow-up and to identify predictors of these outcomes. A retrospective inception cohort of 59 patients diagnosed with JDM was clinically examined in a cross-sectional study a median of 16.8 years (range 2.0-38.1) after symptom onset. Patients were divided by the PRINTO criteria into clinically inactive and active disease. Disease activity was also measured by MDAAT and other validated tools. Medical records were reviewed for early disease variables and medication. By the PRINTO criteria, 31/59 (51%) patients were active and 29/59 (49%) were inactive. By MDAAT, 43/59 (73%) of the patients had measurable disease activity, most commonly found in the skin (59%) and skeletal (27%) systems. MDAAT showed moderate to strong correlations with other disease activity measures (rsp 0.39-0.87, P < 0.05) except for muscle enzymes. Active patients had higher disease activity than inactive patients measured by MDAAT (P < 0.001) and other disease characteristics (all P ≤ 0.002) except for patients' global assessment of disease activity. After controlling for gender and follow-up time, calcinosis during disease-course predicted high MDAAT, age<9 years at diagnosis predicted active disease and organ damage present 6-12 months post diagnosis predicted both outcomes. After 16.8 years, 51-73% of JDM patients had active disease. Disease activity by the PRINTO criteria and MDAAT were moderately to highly associated with most other disease characteristics and was predicted by early damage.

SAT0465 The Myositis Disease Activity Assessment Tool and the Printo Criteria for Clinically Inactive Disease Applied after Long-Term Follow-Up in Juvenile Onset Dermatomyositis.

BackgroundThere is limited knowledge about persistent disease activity and frequency of inactive disease in Juvenile Dermatomyositis (JDM) patients after long-term follow-up.ObjectivesTo apply the Myositis Disease Activity Assessment Tool (MDAAT) and...