OBJECTIVE:

To determine the clinical characteristics and subsets of peripheral blood lymphocytes (PBL), which correlate with decreased disease activity in patients with juvenile dermatomyositis (JDM).

METHODS:

Peripheral blood mononuclear cells from 24 patients with JDM were collected at Mayo Clinic Rochester between 2007 and 2011. These were analyzed using fluorescence-activated cell sorting and flow cytometry. Clinical disease activity was determined by visual analog scales (VAS) collected in 2 consecutive visits and correlated with PBL subsets.

RESULTS:

The change in CD3+CD69+ T cells correlated with the change in global VAS scores. The change in HLA-DR- CD11c+ myeloid dendritic cells also correlated with the change in extramuscular VAS scores. There were trends toward decreased levels of HLA-DR- CD11c+ cells with decreased muscle and global VAS scores, but these did not reach significance. The change in HLA-DR- CD123+ plasmacytoid dendritic cells negatively correlated with the change in muscle VAS scores. Although not statistically significant, decreased levels of CD3-CD16- CD56+ natural killer (NK) cells and HLA-DR- CD86+ myeloid dendritic cells, and increased levels of CD16+CD56- NK cells, correlated with decreased VAS scores.

CONCLUSION:

Changes in CD3+CD69+ T cells, HLA-DR- CD11c+ myeloid dendritic cells, and HLA-DR- CD123+ plasmacytoid dendritic cells are associated with improved clinical course in JDM and could be used as markers for disease activity, but findings need to be verified in a larger, independent cohort. Lack of significant differences among most of our PBL subsets suggests that lymphocyte phenotyping may be difficult to definitively correlate with disease activity in JDM.

OBJECTIVE:

To test 4-year-olds, using the Childhood Myositis Assessment Scale (CMAS) 14 maneuvers, comparing healthy children with those with Juvenile Dermatomyositis (JDM).

METHODS:

Healthy 4-year-olds (n=28) completed the CMAS. Their scores were compared with children with JDM (n=18) who had a muscle Disease Activity Score (DAS-M) of zero.

RESULTS:

The healthy children achieved a mean CMAS score of 46.6 ±2.3 and an inter-quartile range of (46,47). There were no significant differences between boys and girls; the scores were not significantly associated with height or weight. The greatest variation involved items that assessed endurance. Item 1: neck raise, yielded a mean score of 28.2 ±19.3 seconds, with a CMAS score of 2.5 ±0.9, (maximum score = 5). Item 3: leg lift, yielded a mean score of 55.5 ±37.3 seconds, with a mean CMAS score of 3.1 ±1.1, (maximum score = 5). Item 5: sit ups maneuver, yielded a mean score of 5.3 ±1.1 sit ups. Almost identical data were obtained for the 18 treated children with JDM who had normal strength on DAS-M.

CONCLUSION:

Healthy children aged 4 years do not achieve the total CMAS of 52, attained by older children. Both boys and girls were remarkably consistent, with a mean CMAS of 46.6. Children with JDM, age 4 with a DAS-M of zero, also achieved a CMAS of 46.6. We conclude that half of 4-year-old children achieve a CMAS of 46 or 47, not a CMAS of 52, suggesting that weakness may be over diagnosed in 4-year-olds with an inflammatory myopathy. © 2013 by the American College of Rheumatology.

Objective.

Genetic and environmental factors may contribute to the etiology of the juvenile idiopathic inflammatory myopathies (JIIM), systemic autoimmune diseases characterized by muscle and skin inflammation. We investigated the association between ultraviolet radiation (UVR) exposure and the clinical and autoantibody expression of JIIM. Methods. We assessed the relationship between UVR exposure in the month before symptom onset and prevalence of juvenile dermatomyositis (JDM) versus polymyositis (JPM) in 298 patients. Among JDM patients, the association between UVR exposure and myositis autoantibodies was assessed. Regression models were stratified by sex and race. The association between regional UV index in U.S. geoclimatic zones and the clinical and autoantibody subgroups was examined by weighted least squares regression analysis.

Results.

We observed increasing odds of JDM compared with JPM per unit increase in the patients' highest UV index in the month before symptom onset in girls (OR = 1.18; 95% CI = 1.00-1.40). The average and highest UV indices were associated with increasing odds of anti-p155/140 autoantibodies, which was strongest in white males (OR 1.30 and 1.23, respectively). No association was observed between the UV index and anti-MJ autoantibodies or patients without myositis autoantibodies. Across US geoclimatic regions, the average UV index was associated with increasing odds of JDM and anti-p155/140 autoantibodies but decreasing odds of anti-MJ autoantibodies.

Conclusion.

Short-term UVR exposure prior to illness onset may have a role in the clinical and serologic expression of juvenile myositis. Research examining mechanisms of UVR in JIIM pathogenesis is suggested from these findings. © 2013 American College of Rheumatology.

  We report three patients with dermatomyositis (DM) complicated with acute interstitial pneumonia (AIP). All of them complained of fever and acutely worsening dyspnea and were treated immediately by combination therapies with pulse therapy with methylprednisone (mPSL) followed by corticosteroids, biweekly intravenous pulse cyclophosphamide (IVCY) and cyclosporine A (CSA). They recovered rapidly soon after an initiation of this combination regimen. Early intervention with aggressive combination therapy is life-saving for the treatment of AIP in patients with DM.

  Anti-MDA5 antibody is one of the dermatomyositis-specific autoantibodies and anti-MDA5-potsitive patients show characteristic clinical features, such as hypomyositis, high prevalence of acute/subacute interstitial pneumonia (A/SIP) with poor prognosis, hyperferritinemia and elevated hepatobiliary enzyme. We found that serum IL-6, IL-18, M-CSF and IL-10 were significantly higher and serum IL-12 and IL-22 were significantly lower in anti-MDA5-positive patients than in anti-MDA5-negative patients before treatment. Taking together these serological findings, we hypothesized that monocyte and macrophage activation may underlie in the pathophysiology of anti-MDA5-positive patients. They rarely survive after they become to need oxygenation, and so need to be treated as soon as possible once the diagnosis has been made. Intensive regimen of combined immunosuppressive therapy (high-dose corticosteroids, oral cyclosporin and intravenous cyclophosphamide (IVCY, 900-1000 mg/m(2) in every other week)) improved the survival rate of anti-MDA5-positive patients. Especially, the serum ferritin levels tended to go down about 14 days after IVCY, suggesting that IVCY might be a key drug in the treatment of anti-MDA5-positive A/SIP patients.

Juvenile dermatomyositis (JDM) is a systemic, inflammatory, idiopathic disease, mainly affecting the skin and the muscles, starting before the age of 16, with an incidence around one case per 1 million children. Some patients display typical features of JDM without skin involvement, or even without muscle involvement; however, both tissues are affected over time in most cases. Diagnosis criteria were established by Bohan and Peter 35 years ago, based on the presence of typical skin rash and proximal muscle involvement. Other conditions have to be ruled out before making a diagnosis of JDM, such as other connective tissue diseases, polymyositis, infectious/postinfectious myositis, genetic diseases, or metabolic or drug-induced myopathies. Unlike adult-onset dermatomyositis, JDM is exceptionally associated with a malignant disease. JDM may also affect several organs, including the lungs and the digestive tract. In a subset of patients, glucose intolerance, lipodystrophia and/or calcinosis develop. Delay in treatment initiation or inadequate treatment may favor diffuse, debilitating calcinosis. JDM patients have to be referred to reference pediatric centers to properly assess disease activity and disease-related damage (including low bone density in most cases), and to define the best treatment. Long-lasting corticosteroid therapy remains the gold standard, together with physiotherapy. Ongoing clinical trials are assessing the effect of several immunosuppressive and immunomodulatory drugs, which may help to control the disease and possibly demonstrate a corticosteroid-sparing effect. Most patients respond to treatment; relapses are frequent but a complete disease remission is achieved in most cases before adulthood.

The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis.

In this paper, we report our experience with the use of rituximab (RTX) in the treatment of refractory idiopathic inflammatory myopathies (IIM) and review the literature on this topic. Six adult patients (5 female, 1 male) with active IIM, as defined by persistent proximal muscle weakness, elevated serum muscle enzymes, muscle magnetic resonance imaging, electromyographic and histological abnormalities, refractory to at least one immunosuppressant, including methotrexate, were treated with RTX (1,000 mg twice, 2 weeks apart). Patients were regularly followed up for serial assessment of muscle strength by manual muscle test 8 and creatine kinase serum levels. Three patients were affected with polymyositis (PM) and three with anti-t-RNA synthetase syndrome (ASS). A complete B-cell depletion was observed in all patients by 3 months after RTX. A significant clinical improvement was observed in 5 out of 6 cases 6 months after RTX. Only one mild infusion reaction and one case of Herpes zoster infection were observed. A review of the literature to find all the available cases of refractory patients affected with IIM from 1980 to 2012, using the PubMed database, was performed. We were able to find 27 papers, 18 on PM and dermatomyositis and 9 on ASS, including 88 and 40 patients, respectively. A significant improvement was observed in 80 % of patients overall and the drug was well tolerated in the majority of cases. In conclusion, RTX can be considered a therapeutic option in refractory IIM.