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ObjectiveTo refine the spectrum of anti-Ku-associated disease, a condition that is equivocally described by current diagnostic criteria for connective tissue diseases.MethodsAmong 42 consecutive patients harbouring anti-Ku antibodies, subgroups with similar phenotypes and prognosis were delineated without an a priori diagnosis using hierarchical clustering analysis of the cumulative clinico-biological features recorded during the follow-up. Features present at baseline that most efficiently predicted the outcomes were then identified using a sensitivity–specificity sum maximisation approach.ResultsClinico-biological features were clustered into three groups. Glomerulonephritis and ILD, the two fatal complications in this cohort, were unequally distributed between the three clusters that additionally differed on six clinico-biological features.Among features present at baseline, elevated serum level of creatine kinase (CK) and anti-dsDNA antibodies were generally mutually exclusive and most efficiently predicted the cluster belonging at last follow-up. Anti-Ku patients with elevated CK had a 22-fold higher risk of ILD while anti-Ku patients with anti-dsDNA antibodies had a 13-fold higher risk of glomerulonephritisConclusion“Anti-Ku with elevated CK” syndrome and “anti-Ku with anti-dsDNA” syndrome represent two distinct entities that are important to recognise in order to best tailor patient care.

Introduction/objectivesTo describe clinical features in patients with inflammatory myopathies (IMs) from the Argentine Registry of Inflammatory Myopathies, and their relationship with myositis-specific antibodies (MSAs).MethodsThis cross-sectional study included 360 adult patients with dermatomyositis (DM), polymyositis (PM), and inclusion body myositis. Demographics, clinical, and serological characteristics were retrospectively recorded (2016–2019). MSAs were determined by immunoblotting. Patients who were positive for anti-Jo-1, Mi-2, and MDA5 were compared against a group of patients, taken as reference group, who were negative for all MSAs.ResultsWomen 72%, median age at diagnosis was 47.3 years (18–82). The most frequent subtypes were DM (43.9%) followed by PM (30%).The most frequent MSAs were anti-Jo-1 (51/317), 16.1%; MDA5 (12/111), 10.8%, and Mi-2 (23/226), 10.2%. Anti-Jo-1 was associated (p < 0.05) with a higher frequency of chronic disease course, interstitial lung disease (ILD), arthritis, and mechanic’s hands. Anti-Mi-2 was found in patients who had higher frequency of skin manifestations and higher CK values (p < 0.001). Patients with anti-MDA5 had normal or low CK levels. Anti-MDA5 was associated (p < 0.05) with skin manifestations, arthritis, and ILD. The rest of MSAs had frequencies lower than 8%. Anti-TIF1ϒ was found in eight DM patients and one had cancer. Anti-SRP was found in seven patients who had PM and elevated CK.ConclusionAnti-Jo-1 was the most frequent MSA, and was associated with ILD; MDA5 was associated with CADM and ILD, and Mi-2, with classical DM. Despite the different prevalence with respect to other cohorts, the clinical characteristics for each MSA group were similar to the data reported in other studies. Key Points• This study describes the prevalence of MSAs in the Argentine Registry of IMs.• Anti-Jo-1 and anti-MDA5 were associated with ILD.• Anti-Mi-2 was the third most frequent MSA, associated with classical DM.

Objective. Idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases that primarily affect striated muscles; skin, joints, and lungs may be involved with different degrees of severity. Traditional treatment relies on high-dose glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs. Methods. A growing amount of evidence is demonstrating the potential role of novel treatments in the management of IIM. We report our experience with Janus kinase inhibitors (JAKi) in these conditions and review the current evidence for the use of small molecules in real-life clinical practice. Results. A total of 41 papers were retrieved from PubMed, 37 papers concerning IIM and JAKi, and 4 papers concerning IIM and apremilast. Conclusions. An overall good efficacy was evidenced in IIM-associated skin lesions, including rash, ulcers, and calcinosis. If present, muscle and joint involvement demonstrated a good response to therapy, while it was not possible to draw any conclusion about dysphagia. No life-threatening adverse events were reported.

Dropped head syndrome (DHS) is characterized by a passively correctable chin-on-neck deformity inerect posture and can stem from a wide variety of neurological disorders spanning the neuraxis. Neuromuscular disorders account for a major chunk of DHS and include disease of anterior horn celldiseases, polyradiculopathies and cervical plexopathies, disease of neuromuscular junction andmyopathies. Isolated DHS without additional neurological features poses a management challenge, particularly because the symptoms can signifi cantly impact the patient’s quality of life and may notalways respond to treatment..(Ref)Here we present a patient with isolated DHS with evaluation revealingisolated next extensor myopathy with remarkable response to treatment. Although isolated neckextensor myopathy typically exhibit poor immunomodulatory response, timely identifi cation and earlyintervention probably can lead to a favourable outcome in a subgroup of patients.

Purpose of review To analyze and provide an update of the current therapeutic strategies on immune checkpoint inhibitor-related myositis, including forms with concurrent myocarditis and/or myasthenia. Moreover, we aim to assess the risk of rechallenging with ICI as well as the potential abrogation of antitumor immunity with the immunosuppressive therapy. Recent findings Therapeutic recommendations indicate that the best initial approach in patients with myositis is withholding ICI therapy and initiating treatment with corticosteroids. In severe forms, the use of intravenous immunoglobulins, plasma exchange, or additional oral immunosuppressants should be considered. The benefit of new biological drugs has recently been pointed out, highlighting IL-6 receptor inhibitors and Janus kinase inhibitors. Summary Corticosteroids are considered as the first-line therapy for patients with myositis. Intensive or rescue therapies may be useful in corticosteroid-refractory patients as well as in those with myasthenia or myocarditis. Prospective studies are needed to better understand the mechanism of myositis so that new targeted therapies could arise. Further research is key to improve the therapeutic options that lead to resolution of ICI-related adverse events while preserving antitumor effects.

Purpose of Review Systemic sclerosis (SSc) and myositis are two different entities that may coexist as an overlap syndrome. Immunological biomarkers such as anti-PM/Scl or anti-Ku reinforce the syndrome. This review is focused on the treatment of different and characteristic manifestations of this syndrome. Recent Findings Among the different phenotypes of muscle involvement in patients with SSc, the fibrotic pattern and the sporadic inclusion body myositis must be identified early to avoid a futile immunosuppressive treatment. Other forms such as dermatomyositis, non-specific myositis, and immune-mediated necrotizing myopathy need to receive conventional immunosuppressive therapy considering that high dose of glucocorticoids may induce a scleroderma renal crisis in patients with SSc. Physicians must be aware of the existence of a “double trouble” association of hereditary myopathy with an autoimmune phenomenon. Several autoantibodies, mainly anti-PM/Scl and anti-Ku, may help to define specific phenotypes with characteristic clinical manifestations that need a more specific therapy. Vasculopathy is one of the underlying mechanisms that link SSc and myositis. Recent advances in this topic are reviewed. Summary Current treatment of SSc-associated myopathy must be tailored to specific organs involved. Identifying the specific clinical, pathological, and immunological phenotypes may help to take the correct therapeutic decisions.

Purpose of Review Immune-mediated necrotizing myositis (IMNM) is a rare autoimmune disorder characterized by proximal muscle weakness, elevated creatine kinase levels, and necrosis of muscle fibers. While the exact pathogenesis of IMNM remains unknown, anti-HMGCR and anti-SRP autoantibodies are associated with different predisposing factors, clinical manifestations, and severity of the disease and are believed to correspond to two pathogenically distinct entities. The cornerstone treatment for IMNM is a combination of glucocorticoids and steroid-sparing agents. Therapeutic strategies aimed at decreasing the half-life of endogenous autoantibodies, such as intravenous immunoglobulin (IVIG), or reducing their production, such as rituximab, have shown promise as powerful treatments. In severe cases, combining IVIG and rituximab can have synergistic effects. Recent Findings Previous studies suggested that complement dysregulation may be involved in the pathogenesis of IMNM. However, a recent phase 2 clinical trial evaluating the effectiveness of zilucoplan, a C5 inhibitor, failed to show efficacy in IMNM. Summary In this review, we aim to provide a comprehensive review of IMNM focusing on the current evidence regarding treatment options for this condition. Our goal is to present an up-to-date overview of the current state of therapeutics on IMNM and highlight potential areas for future investigation.

Purpose of Review Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous autoimmune diseases characterized by muscular but also extra-muscular systemic manifestations. IIM may induce severe muscle impairment and be associated with life-threatening complications. Current therapeutic approach includes the combination of corticosteroids (CS) with immunosuppressants (IS). IIM often require prolonged treatment duration, and it is not uncommon that patients present refractory and/or relapsing disease course. CS and IS therapy exposes patients to significant adverse events. Intravenous immunoglobulins (IVIG) have demonstrated their efficacy in many autoimmune diseases and have a better safety profile. This article reviews current evidence on the use of IVIG in IIM and provides guidance for their use in clinical practice. Recent Findings IVIG have been used worldwide for many years to treat autoimmune diseases. Historically, IVIG have been studied in IIM patients that were categorized in polymyositis and dermatomyositis (DM). Recent studies demonstrated the efficacy of IVIG in DM, and recent classification criteria reconsider the entity of polymyositis. Summary IVIG are at least partially effective in all IIM subgroups, except IBM. In addition to DM, growing set of data suggests IVIG efficacy in Immune-mediated necrotizing myopathies, but controlled studies are still needed. Improvement in our understanding of pathophysiology in each IIM subgroup should allow performing specific clinical trials.

Purpose of Review Immune-mediated necrotizing myositis (IMNM) is the latest identified subgroup of idiopathic inflammatory myopathies (IIM). IMNM delineates a homogeneous group of patients with the same phenotype and outcome. We reviewed the clinical presentation as well as the myopatological findings in IMNM patients. We highlighted the diagnostic criteria and the importance of IMNM specific autoantibodies for both the diagnosis and the prognosis. IMNM may induce severe muscle damages and may be associated with a poor muscle strength recovery. We reported the current knowledge concerning the pathomechanisms of the disease as well as the current therapeutic approaches. Recent Findings Recent studies suggested the role of complement cascade and the autoantibodies in the pathomechanisms. This observation opens new therapeutic avenues. Summary IMNM is a muscle-specific autoimmune disease. IMNM patients have the most severe muscle involvement compared to other IIM. Pathophysiological mechanisms are being clarified which should improve patient management.