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Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

Introduction: The clinical characteristics of patients positive for anti-small ubiquitin-like modifier 1-activating enzyme subunit 1 (SAE1) antibodies and diagnosed with idiopathic inflammatory myopathies (IIMs) vary across different cohorts and ethnicities, particularly concerning interstitial lung disease (ILD). We aimed to assess the clinical utility of the line immunoblot assay (LIA) in detecting anti-SAE1 autoantibodies and evaluate the clinical relevance and chronology of ILD development in relation to SAE1 autoantibody positivity among Taiwanese patients. Methods: We retrospectively conducted a population-based cohort analysis involving 6,496 patients who visited Chang Gung Memorial Health System across Taiwan from May 2018 to December 2021. Patients were assayed for myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) using the LIA method, and the antinuclear antibody (ANA) indirect immunofluorescence (IIF) method was used to evaluate ANA patterns. Of these, 70 SAE1-positive patients (1.08%) were included and followed up until December 2023. Associations with clinical characteristics and final diagnosis, particularly ILD, were assessed. Results: Among the 70 SAE1-positive patients, 10 (14.3%) were strongly positive and 60 (85.7%) were weakly positive. In the strong positive group, 70% (7/10) were diagnosed with IIM, with most (5/7) showing a concordant ANA IIF pattern (speckled type). Six patients presented ILD either before (1/6) or after (5/6) IIM diagnosis; the majority (4/6) were classified as organizing pneumonia. The remaining 30.0% (3/10) had connective tissue disease (CTD) other than IIM without detectable ILD during follow-up, and none demonstrated a concordant ANA IIF pattern. In the weakly positive group, only 5.0% (3/60) had IIM and 3.3% (2/60) had ILD. The positive predictive value for strong positive SAE1 autoantibodies in diagnosing IIM was significantly higher than for weak positives (70.0% vs. 5.0%; p < 0.001). Conclusions: The study suggests that strong positive SAE1 autoantibodies detected via LIA are more closely associated with IIM compared to weak positive results. A high prevalence of ILD was observed among strong positive Taiwanese patients, indicating the need for prompt screening. Patients with weak positive or discordant ANA IIF results may represent false positives with a lower ILD risk. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIMs) encompass a spectrum of autoimmune diseases characterized by muscle inflammation and systemic involvement. This review aimed to synthesize current evidence on the clinical significance and pathogenic mechanisms underlying autoantibodies associated with IIMs. Autoantibodies targeting aminoacyl-tRNA synthetases (ARS) play a pivotal role in antisynthetase syndrome (ASS), highlighting associations with interstitial lung disease (ILD) and distinctive clinical features. Anti-Mi-2 antibodies in dermatomyositis (DM) are hallmarked by characteristic cutaneous manifestations and favorable prognostic outcomes. Conversely, anti-TIF1 antibodies are correlated with DM and a higher risk of malignancies, implicating CD8+ T cells in its pathogenesis. Anti-MDA5 antibodies signify clinically amyopathic DM (CADM) with severe ILD, linked to dysregulated neutrophil extracellular trap (NET) formation. In immune-mediated necrotizing myopathies (IMNMs), anti-SRP and anti-HMGCR antibodies induce complement-mediated myopathy, typically following statin exposure. Additionally, anti-TRIM72 antibodies emerge as potential diagnostic markers in IIMs. Anti-cN1A autoantibodies are linked to inclusion body myositis (IBM) and play a decisive role in muscle protein degradation. Meanwhile, anti-FHL1 autoantibodies are associated with severe disease manifestations and muscle damage, as established in experimental models. Anti-eIF3 autoantibodies, recently identified in polymyositis (PM) patients, are rarely detected (<1%) and associated with a favorable prognosis. Elucidating these autoantibodies is anticipated to not only assist in early diagnosis and disease stratification but also inform targeted therapeutic interventions, emphasizing the intricate interplay between autoimmunity, cellular dysfunction, and clinical outcomes in IIMs. [ABSTRACT FROM AUTHOR]

Background: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. Case presentation: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. Conclusions: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a progressive, multiorgan disease with limited treatment options. Although a recent proof-of-concept study using romilkimab or SAR156597, a bispecific IL-4/IL-13 antibody, suggests a direct role of these cytokines in the pathophysiology of SSc, their contributions to the balance between inflammation and fibrosis are unclear. Here, we determine the roles of type 2 inflammation in fibrogenesis using FRA2-Tg (Fos-related antigen 2-overexpressing transgenic) mice, which develop spontaneous, age-dependent progressive lung fibrosis. We defined the molecular signatures of inflammation and fibrosis at three key stages in disease progression, corresponding to preonset, inflammatory dominant, and fibrosis dominant biology, and revealed an early increase in cytokine-cytokine receptor interactions and antigen-processing and presentation pathways followed by enhanced Th2- and M2 macrophage-driven type 2 responses. This type 2 inflammation progressed to extensive fibrotic pathology by 14-18 weeks of age, with these gene signatures overlapping significantly with those seen in the lungs of patients with SSc with interstitial lung disease (ILD). These changes were also evident in the histopathology, which showed perivascular and peribronchiolar inflammation with prominent eosinophilia and accumulation of profibrotic M2-like macrophages followed by rapid progression to fibrosis with thickened alveolar walls with multifocal fibrotic bands and signs of interstitial pneumonia. Critically, treatment with a bispecific antibody targeting IL-4 and IL-13 during the inflammatory phase abrogated the Th2 and M2 responses and led to near-complete abrogation of lung fibrosis. These data recapitulate important features of fibrotic progression in the lungs of patients with SSc-ILD and enhance our understanding of the progressive pathobiology of SSc. This study also further establishes FRA2-Tg mice as a valuable tool for testing future therapeutic agents in SSc-ILD. [ABSTRACT FROM AUTHOR]

The presence of interstitial lung disease (ILD) is a common and fearsome feature of idiopathic inflammatory myopathies (IIM). Such patients show radiological pattern of non-specific interstitial pneumonia (NSIP). The present study aimed to assess the prevalence of myositis-specific and myositis-associated antibodies (MSA and MAA) in a cohort of patients with a previous diagnosis of NSIP and no sign or symptom of IIM. Secondly, it will be assessed whether patients displaying MSA and/or MAA positivity have a worse or a better outcome than idiopathic NSIP. All patients affected by idiopathic NSIP were enrolled. MSA and MAA were detected using EUROLINE Autoimmune Inflammatory Myopathies 20 Ag (Euroimmun Lubeck, Germany), line immunoassay. A total of 16 patients (mean age 72 ± 6.1 years old) were enrolled. Six out of 16 patients (37.5%) had significant MSA and/or MAA positivity: one displayed positivity of anti-PL-7 (+ +), one of anti-Zo (+ +), anti-TIF1γ (+ + +) and anti-Pm-Scl 75 (+ + +), one of anti-Ro52 (+ +), one of anti-Mi2β (+ + +), one of anti-Pm-Scl 75 (+ + +) and the latter of both anti-EJ (+ + +) and anti-Ro52 (+ + +). Two out of 7 seropositive patients showed a significant impairment of FVC (relative risk 4.8, 95% CI 0.78–29.5; p = 0.0350). Accordingly, among the 5 patients that started antifibrotic treatment during the observation time, 4 were seronegative. Our findings highlighted a potential autoimmune or inflammatory in idiopathic NSIP patients and also in those without significant rheumatological symptoms. A more accurate diagnostic assessment may ameliorate diagnostic accuracy as well as may provide new therapeutic strategy (antifibrotic + immunosuppressive). A cautious assessment of NSIP patients with a progressive and non-responsive to glucocorticoids disease course should therefore include an autoimmunity panel comprising MSA and MAA. [ABSTRACT FROM AUTHOR]

Objective: There has been an increasing number of literature related to idiopathic inflammatory myopathies (IIM) in the past few decades. However, there is a lack of intuitive and systematic analysis of research on IIM. Therefore, this study aimed to perform a bibliometric analysis to identify the current trends and hotspots of research on IIM. Methods: Articles and reviews on IIM published during 1982–2021 were acquired from the Web of Science Core Collection (WoSCC) database. VOSviewer application was applied to conduct a network analysis of the keywords, institutions, and countries. The top 100 most-cited publications regarding IIM were analyzed. Results: In total, 665 publications were included. Globally, the USA produced the most articles on IIM (144). Karolinska Institutet was the institution with the most outputs (47). Rheumatology ranked on top of journals, with 47 IIM-related documents collecting a total of 1420 citations. In the area of IIM documents, biomarkers were the most common research theme. According to the co-occurrence analysis of keywords, "cardiac involvement," "criteria," and "refractory adult" were identified as significant future research centers. Conclusion: The scientific literature on IIM has advanced rapidly in the past 4 decades. The classification criteria, treatment, and extramuscular manifestations of IIM have been identified as promising research frontiers in the field. The global status and trends of the IIM literature from a bibliometric aspect can offer a helpful guidance and new insight for researchers and medical workers in the domain. Key Points • This study reveals the topic trends and knowledge structure of idiopathic inflammatory myopathies literature over the last 40 years. • This study identifies potential future research hotspots, including "cardiac involvement," "criteria," and "refractory adult." [ABSTRACT FROM AUTHOR]

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST−/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36–0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20–440) per 100,000 person-years), both probable de novo infections. Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. What is Known: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. What is New: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases. [ABSTRACT FROM AUTHOR]

We describe the first case of antisynthetase syndrome (ASS) with antibodies to anti‐glycyl tRNA synthetase (EJ‐1) with antiphospholipid syndrome (APLS). A 66‐year‐old man presented with progressive dyspnoea, fever, dry cough and proximal muscle weakness over several months on a background of cryptogenic organizing pneumonia. Examination revealed bibasal fine chest crackles, proximal muscle weakness of the upper and lower limbs, digital skin thickening and facial telangiectasias. Creatine kinase was elevated and autoimmune screening was positive for anti‐EJ‐1, anti‐beta‐2‐glycoprotein, anti‐Ro and anti‐La antibodies. Computed tomography of the chest revealed a usual interstitial pneumonia pattern and a ventilation–perfusion scan demonstrated scintigraphic evidence of bilateral pulmonary emboli. A diagnosis of ASS and APLS was made. Immunosuppressive therapy including pulsed methylprednisolone, rituximab and mycophenolate was commenced with improvement in symptoms. This case highlights the importance of evaluation for ASS in idiopathic interstitial pneumonia, and APLS in ASS patients. [ABSTRACT FROM AUTHOR]

Anti-synthetase syndrome (ASSD) is an autoimmune disease characterized by the presence of autoantibodies targeting one of several aminoacyl t-RNA synthetases (aaRSs) along with clinical features including interstitial lung disease, myositis, Raynaud's phenomenon, arthritis, mechanic's hands, and fever. The family of aaRSs consists of highly conserved cytoplasmic and mitochondrial enzymes, one for each amino acid, which are essential for the RNA translation machinery and protein synthesis. Along with their main functions, aaRSs are involved in the development of immune responses, regulation of transcription, and gene-specific silencing of translation. During the last decade, these proteins have been associated with cancer, neurological disorders, infectious responses, and autoimmune diseases including ASSD. To date, several aaRSs have been described to be possible autoantigens in different diseases. The most commonly described are histidyl (HisRS), threonyl (ThrRS), alanyl (AlaRS), glycyl (GlyRS), isoleucyl (IleRS), asparaginyl (AsnRS), phenylalanyl (PheRS), tyrosyl (TyrRS), lysyl (LysRS), glutaminyl (GlnRS), tryptophanyl (TrpRS), and seryl (SerRS) tRNA synthetases. Autoantibodies against the first eight autoantigens listed above have been associated with ASSD while the rest have been associated with other diseases. This review will address what is known about the function of the aaRSs with a focus on their autoantigenic properties. We will also describe the anti-aaRSs autoantibodies and their association to specific clinical manifestations, and discuss their potential contribution to the pathogenesis of ASSD. [ABSTRACT FROM AUTHOR]

Introduction/objectives: To describe clinical features in patients with inflammatory myopathies (IMs) from the Argentine Registry of Inflammatory Myopathies, and their relationship with myositis-specific antibodies (MSAs). Methods: This 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. Results: Women 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. Conclusion: Anti-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. [ABSTRACT FROM AUTHOR]

Background: Rare diseases (RDs) affect less than 5/10,000 people in Europe and fewer than 200,000 individuals in the United States. In rheumatology, RDs are heterogeneous and lack systemic classification. Clinical courses involve a variety of diverse symptoms, and patients may be misdiagnosed and not receive appropriate treatment. The objective of this study was to identify and classify some of the most important RDs in rheumatology. We also attempted to determine their combined prevalence to more precisely define this area of rheumatology and increase awareness of RDs in healthcare systems. We conducted a comprehensive literature search and analyzed each disease for the specified criteria, such as clinical symptoms, treatment regimens, prognoses, and point prevalences. If no epidemiological data were available, we estimated the prevalence as 1/1,000,000. The total point prevalence for all RDs in rheumatology was estimated as the sum of the individually determined prevalences.Results: A total of 76 syndromes and diseases were identified, including vasculitis/vasculopathy (n = 15), arthritis/arthropathy (n = 11), autoinflammatory syndromes (n = 11), myositis (n = 9), bone disorders (n = 11), connective tissue diseases (n = 8), overgrowth syndromes (n = 3), and others (n = 8). Out of the 76 diseases, 61 (80%) are classified as chronic, with a remitting-relapsing course in 27 cases (35%) upon adequate treatment. Another 34 (45%) diseases were predominantly progressive and difficult to control. Corticosteroids are a therapeutic option in 49 (64%) syndromes. Mortality is variable and could not be determined precisely. Epidemiological studies and prevalence data were available for 33 syndromes and diseases. For an additional eight diseases, only incidence data were accessible. The summed prevalence of all RDs was 28.8/10,000.Conclusions: RDs in rheumatology are frequently chronic, progressive, and present variable symptoms. Treatment options are often restricted to corticosteroids, presumably because of the scarcity of randomized controlled trials. The estimated combined prevalence is significant and almost double that of ankylosing spondylitis (18/10,000). Thus, healthcare systems should assign RDs similar importance as any other common disease in rheumatology. [ABSTRACT FROM AUTHOR]

Antisynthetase syndrome (ASS) is a rare autoimmune disease that is clinically manifested with interstitial lung disease (ILD), inflammatory myopathies, inflammatory arthritis, skin hyperkeratosis, and Raynaud's phenomenon. The pathophysiology of ASS is not clearly understood but the presence of anti-aminoacyl-tRNA appears to be a marker of ASS. The most common and first identified of anti-aminoacyl-tRNA antibody is anti-Jo-1. Being a rare and hardly diagnosed entity, we present a 33-year-old woman referring to the hospital with fever, dry cough and dyspnea in the postpartum period. She had Raynoud's phenomena and her upper extremity power was decreased. High resolution computed tomography and pulmonary function test were performed, and these tests were consistent with ILD. Electromyographic revealed myopathy. Her anti-Jo-1 was positive. She was diagnosed with ASS and administered immunosuppressive medications. [ABSTRACT FROM AUTHOR]

Background: Anti-synthetase syndrome (ASS) is an uncommon immune-mediated entity characterized by myositis, interstitial lung disease (ILD), non-erosive arthritis, and less common features such as fever, Raynaud's phenomenon, and skin changes in association with anti-aminoacyl-transfer-RNA antibodies, most commonly anti-Jo-1 antibodies.Case Presentation: We present a challenging and rare case of ASS-associated ILD presenting with unexplained respiratory symptoms and bilateral infiltrates on chest imaging during the COVID-19 pandemic. High clinical suspicion for ASS with early appropriate therapy with corticosteroids and immunosuppressive agents led to marked clinical improvement.Conclusion: High index of suspicion for ASS is mandated in patients with unexplained ILD. A comprehensive autoimmune work-up is important as an early treatment with corticosteroids with or without immunomodulators improves patient outcomes and survival in an otherwise poor prognostic disease. [ABSTRACT FROM AUTHOR]

Purpose: Antisynthetase syndrome (ASS) is a rare systemic autoimmune condition associated to the presence of anti-aminoacyl-tRNA synthetase antibodies. Interstitial lung disease (ILD) is the most prevalent manifestation of ASS and is a major determinant of morbidity and mortality. The aim of this study was to describe the radiological characteristics of patients with ASS-associated-ILD in our institution. Materials and methods: Medical records from 2014 to 2020 were retrospectively reviewed and patients with a diagnosis of ASS and evidence of ILD on HRCT were included. HRCT images were reviewed by two thoracic radiologists in consensus. Five HRCT patterns were defined: cellular non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), mixed NSIP/OP pattern, acute interstitial pneumonia (AIP) pattern and fibrotic pattern. Descriptive statistics was calculated for all variables. Results: Twenty-two patients with ASS who met inclusion criteria were included. The disease presented with the typical triad of ASS in 45% of patients, 55% had ILD only at the onset. Cellular NSIP was present in 27% of patients, OP in 23%, mixed NSIP/OP in 9%, AIP in 18% and a fibrotic pattern in 23%. Conclusion: HRCT findings in ASS-associated ILD are often non-specific; nevertheless, it is important to consider this diagnosis, especially in patients presenting with acute onset of symptoms. [ABSTRACT FROM AUTHOR]

Behçet's disease is a chronic, multisystem inflammatory disorder characterized by relapsing inflammation. Although its etiopathogenesis has not yet been clarified, both the adaptive and innate immune systems, genetic predisposition, and environmental factors have all been implicated. It is more frequent and more severe in males in the third and fourth decades of life. The eye is the most frequently involved organ in the course of the disease. Ocular involvement (Behçet's uveitis) is characterized by bilateral recurrent non-granulomatous panuveitis and occlusive retinal vasculitis. Recurrent inflammatory episodes in the posterior segment may lead to permanent vision loss due to irreversible retinal damage and complications such as macular scarring, macular atrophy, and optic atrophy. Early and aggressive immunomodulatory treatment and the use of biologic agents when needed are crucial for preventing recurrences and improving visual prognosis. [ABSTRACT FROM AUTHOR]

Inflammatory arthritis is a common feature of antisynthetase syndrome. Ultrasonography is able to characterize important features of bone and tendon pathology but has not been evaluated in this setting. We review the sonographic findings in a series of patients with antisynthetase syndrome and inflammatory arthritis. A retrospective chart review was performed of patients with antisynthetase syndrome-associated inflammatory arthritis who had undergone ultrasound imaging for joint pathology. Seventeen sonographic assessments of eight patients were included. Synovial hypertrophy was seen in all eight patients, with active Doppler signal present in six patients (13 of 17 ultrasound locations). Tendon involvement was common, with tenosynovitis in seven patients (11 of 17 ultrasound locations). Erosions were present in five patients. Musculoskeletal ultrasound showed significant joint pathology including proliferative synovitis and tenosynovitis. This may be severe and associated with erosive disease. Further systematic studies are needed to better understand the articular involvement of antisynthetase syndrome. Key points • Marked inflammatory change—with proliferative synovitis, tenosynovitis, and erosions—can be seen in selected patients with antisynthetase syndrome (ASyS). • Inflammatory arthritis from ASyS can be severe and erosive in the absence of RF and ACPA and can be refractory to immunosuppressive therapy used to manage the myositis and interstitial lung disease. • Systematic sonographic evaluation of patients with ASyS is needed to further evaluate pathology and treatment response of inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Immunofluorescence on HEp2-cells is the standard diagnostic assay for the detection of anti-nuclear antibodies (ANA). Cytoplasmic speckled patterns are a common finding, and are associated with various antibodies, including anti-synthetase antibodies. However, classic ENA testing generally identifies only anti-Jo-1. Moreover, anti-synthetase syndrome is increasingly recognized as a pleomorphic entity, possibly presenting as isolated arthritis or interstitial lung disease. Sera referred for routine ANA testing were selected on the basis of the presence of a fine dense speckled cytoplasmic pattern (254 samples) and compared to control sera with negative cytoplasm (239 samples). All 493 samples were tested with a commercial synthetase profile dot-blot (D TEK - Alphadia-Alifax) including anti-Jo1, anti-PL7, anti-PL12, anti-EJ, anti-OJ, anti-KS, anti-ZO, anti-HA, anti-SRP, and anti-Ribosome P0. Retrospective clinical data was searched for positive patients. Dot-blot identified 18/254 (7.1%) positive sera in the samples with a cytoplasmic fluorescence pattern and 4/239 (1.7%) in the control group (χ2 = 8.4627; p = 0.003625). Blot intensity was more intense in samples with concordant cytoplasmic staining (cytoplasmic negative 27 ± 12.4; cytoplasmic positive 53.9 27 ± 27.7; p = 0.0027). In the positive samples, 8/18 had a highly compatible diagnosis (myositis, interstitial lung disease, arthritis), 7/18 an uncharacterized connective tissue disease, and 3 a diagnosis not associated with the presence of anti-synthetase antibodies. We evaluated the performance of a dot-blot assay for anti-cytoplasmic antibodies in a serologic cohort presenting a cytoplasmic speckled pattern found during routine ANA testing. This algorithm enabled the identification of a significant quota of patients with rare anti-synthetase antibodies and an incomplete or atypical clinical picture. Reflex testing strategies of speckled cytoplasmic patterns with multiplex assays containing cytoplasm-specific antigens, as opposed to standard ENA testing, may yield important data and for this reason should be implemented in routine ANA testing. [ABSTRACT FROM AUTHOR]

Inflammatory idiopathic myopathies are a group of autoimmune diseases affecting predominantly the proximal skeletal muscles, with raised muscle enzymes, with or without skin involvement and extramuscular organ involvement. Autoantibodies help to characterize patients into different clinical phenotypes. Successful treatment necessitates controlling inflammation early with corticosteroids and invariably requires additional immunosuppressive therapy. This review focuses on the aetiology, pathogenesis, clinical presentation, investigations and management of patients presenting with inflammatory idiopathic myopathies, predominantly focusing on polymyositis and antisynthetase syndrome. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics. [ABSTRACT FROM AUTHOR]