Positive Myositis Research Articles

NCMP-02. UTILITY OF ICE PACK TEST FOR EARLY RECOGNITION OF IMMUNE CHECKPOINT INHIBITOR MEDIATED OCULAR WEAKNESS

Abstract INTRODUCTION Immune checkpoint inhibitors (ICI) are associated with neurological immune-related adverse events (NiArE) such as myasthenia gravis (MG) and myositis. These conditions often present with overlapping symptoms, notably ptosis, dyspnea, and extremity weakness. Early recognition and treatment are warranted to prevent disease progression. OBJECTIVE To test the utility of simple bedside ice pack test (IPT) in early recognition and distinction of ICI-mediated MG and myositis ocular manifestations. METHODS We administered IPT in 14 patients who had received ICI in the past 6 months and presented with ptosis. Improvement in ptosis was considered positive IPT (non-fixed, fatigable ptosis) that is suggestive of Immune-mediated MG-predominant process. Work up included myasthenia antibodies, EMG, serum markers of muscle injury (creatine kinase, aldolase), myositis panel and muscle biopsy. Statistical analyses employed median for continuous and frequencies for categorical variables. RESULTS Positive IPT was found in 2 (14%) patients with positive myasthenia antibodies and neuromuscular junction dysfunction on EMG in one patient with repetitive nerve stimulation. These patients had mild elevation in creatine kinase (CK). Muscle biopsy did not reveal a myositic process. Twelve (86%) patients had negative IPT (fixed and non-fatigable ptosis) with significantly elevated CK (>4000), positive myositis panel and muscle biopsy consistent with myositic process. Six of these patients (42%) also had positive myasthenia antibodies. Concomitant myocarditis was observed in 5 (36%) patients. CONCLUSION Clinical overlap between myasthenia and myositis is observed in immune mediated toxicity that may be due to cross-reactivity of antibodies, however, IPT was able to distinguish MG vs myositis-predominant process, thus helping guide management.

Comprehensive Enteroviral Serology Links Infection and Anti-Melanoma Differentiation-Associated Protein 5 Dermatomyositis.

Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic autoimmune diseases characterized by specific clinical features and, frequently, skeletal muscle inflammation. Specific subtypes of IIMs can be characterized by myositis-specific autoantibodies and are associated with distinct clinical phenotypes. Here, we focus on anti-melanoma differentiation-associated protein 5 (MDA5)-positive myositis and anti-signal recognition particle (SRP)-positive myositis, both of which exhibit seasonality but lack known environmental triggers. We employed Phage ImmunoPrecipitation Sequencing to profile serum antibodies against the human proteome, the human virome, and a comprehensive enterovirus library. We analyzed sera from 57 patients with anti-MDA5 autoantibodies and 57 patients with anti-SRP autoantibodies, as well as 57 healthy controls. All groups were matched for age, sex, and race. Our autoantibody profiling results define specific immunogenic regions within the MDA5 and SRP autoantigens. We also discovered that in MDA5 sera, versus SRP sera, there was an elevated antibody response to the viral capsid protein 1 (VP1) of enterovirus B, which was accompanied by a decreased antibody response to rhinovirus A. Considering the role of MDA5 as a sensor of picornaviral infections and a mediator of inflammatory signaling, our data suggest a novel etiologic link between enterovirus infection and anti-MDA5 dermatomyositis.

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis

BackgroundThe increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468.). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice.MethodsA monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out.ResultsIn the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed.ConclusionsIn our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

Positive predictive value of myositis antibody line blot testing in patients with suspected idiopathic inflammatory myopathy.

Line blot (LB) is in widespread use for myositis antibody detection. Yet, studies of its positive predictive value (PPV) in patients with suspected idiopathic inflammatory myopathy (IIM), which would be of particular relevance to neuromuscular clinicians, are lacking. We aimed to determine the PPV of myositis antibody LB testing in patients with suspected IIM, and examine whether PPV was significantly impacted by intensity of antibody positivity. This was a retrospective study of patients who underwent myositis antibody LB testing for suspected IIM between March 2019 and August 2022. Of 70 patients who underwent testing for suspected IIM and had positive myositis antibody LB results, 43 (61%) were female and the median age was 61 years (range: 10-83 years). Forty-four were classified as true-positives, yielding a PPV of 63%. The PPV of patients with weak-positive myositis antibody results (14/30, 47%) was significantly lower than the PPV of patients with moderate-positive or strong-positive myositis antibody results (30/40, 75%) (p = .02). Our study found that myositis antibody LB testing in patients with suspected IIM had a modest PPV, underscoring the need for antibody interpretation in the context of all available clinical and ancillary test data to avoid misdiagnosis. The significantly lower PPV in patients with weak-positive results emphasizes the particular importance of clinical correlation in such patients. Further study into the diagnostic performance of various LBs for myositis antibody detection is needed to inform their interpretation in clinical practice.

Novel uses of complement inhibitors in myasthenia gravis-Two case reports.

Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MGreceiving concomitant pembrolizumab. This was a retrospective review of two medical records. Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58-year-old male had refractory thymoma-associated AChR ab-positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri-infusion pulse prednisone. MG remained stable and he continues eculizumab. In the first patient, eculizumab, followed by ravulizumab, improved ICI-MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI-induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.

Unusual presentation of antisynthetase syndrome: a case series and review of the literature

BackgroundAntisynthetase syndrome is an inflammatory myopathy that is characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies. Only 30% of those who suffer from the disease can be identified. We present three Hispanic cases of antisynthetase syndrome with unusual clinical pictures were extended myositis panel results enable disease diagnosis and treatment.Case presentationA 57-year-old Hispanic/Latino female with an erythematous scaly plaque, unresolved fever and non-immune haemolytic anaemia in whom inpatient work-up for fever of unknown origin was positive for anti-PL12 positive myositis extended panel. A 72-year-old Hispanic/Latino male with amyopathic weakness syndrome and mechanic hands in whom impatient work-up was relevant for proximal muscle uptake and anti-PM75 and AntiPL-12 myositis extended panel. And a 67-year-old Hispanic/Latino male with progressive interstitial lung disease and unresolved fever ended in myositis extended panel positive for antiPL-7. After systemic immunosuppressor treatment, patients had favourable clinical and paraclinical responses during outpatient follow-up.ConclusionsThe high variability of the antisynthetase syndrome in these cases demonstrates the importance of identification through an expanded panel and highlights the probability that this is a variable disease and that we need to include emerging molecular tests to promote the timely treatment of patients.

Magnetic resonance imaging findings of the lower limb muscles in anti-mitochondrial M2 antibody-positive myositis

Anti-mitochondrial M2 antibody (AMA-M2)-positive myositis is an idiopathic inflammatory myopathy (IIM). Of all patients with myositis, 2.5–19.5% have AMA-M2 antibodies. However, the detailed distribution of muscles affected in AMA-positive myositis is unknown. Therefore, we examined lower muscle magnetic resonance imaging (MRI) findings of patients with AMA-positive myositis. Among the 63 patients with IIM at our institute, 5 (7.9%) were positive for AMA-M2 antibodies. However, one was also positive for anti-Jo1 antibodies; therefore, four patients were finally participated in this study. All patients had high-intensity MRI signals in the proximal muscles, including the gluteus maximus and iliopsoas muscles, and in the thigh muscles, including the vastus lateralis, vastus medialis, adductor magnus, and semimembranosus muscles. Lower leg muscles were relatively spared. Fascial edema was observed in all patients and was also present in the lower leg muscles. Subcutaneous edema was observed, particularly in the proximal portion of the lower limbs. In AMA-positive myositis, proximal muscles, including the gluteus maximus, vastus lateralis, adductor magnus, and the semimembranosus, were markedly affected, while the lower leg muscles were relatively preserved. Additionally, fascial edema was evident even in lower leg muscles. Therefore, muscle MRI can be a useful diagnostic aid for AMA-positive myositis.

“Playing detective” in a case of paraneoplastic polymyositis

Adult-onset polymyositis (PM) belongs to the idiopathic inflammatory myopathy (IIM) group and manifests with proximal muscle weakness, elevated muscle enzymes and positive myositis- specific antibodies. The subset of autoantibodies can indicate a higher risk for cancer association. An 82-year-old diabetic patient, with multiple cardio-vascular comorbidities, was hospitalized for muscle weakness of the upper girdle, dysphagia and dysphonia, accompanied by elevated serum muscle enzymes. Muscle biopsy showed an inflammatory infiltrate while immunological assays found positive ANA and anti-NXP2 antibodies. The diagnosis of PM was established, thus a screening for underlying neoplasia was required. Upper endoscopy visualized an area of ectopic mucosa in the esophagogastric junction and the biopsy confirmed a squamous cell carcinoma in situ. Patient had favorable muscle outcome under methylprednisolone pulse therapy. It is worth noting that polymyositis is more rarely associated with cancers as compared to dermatomyositis (DM). In conclusion, the type of antibodies identified in myositis can represent an alarm signal for oncologic screening, making possible an early diagnosis and efficient treatment of a hidden tumor.

The effect of immunosuppressive therapy on cardiac involvements in anti-mitochondrial antibody-positive myositis.

Anti-mitochondrial antibody (AMA)-positive myositis is frequently associated with various cardiac involvements, such as arrhythmia and left ventricular (LV) dysfunction. However, the efficacy of immunosuppressive therapy in these complications remains unknown. This study aimed to investigate the cardiac response to immunosuppressive therapy in patients with AMA-positive myositis. The clinical data of 15 AMA-positive myositis patients with cardiac involvement were retrospectively collected at our centre. To evaluate the effects of immunosuppressive therapy, echocardiographic and laboratory data of patients who received glucocorticoid therapy with additional immunosuppressants (n=6) and those who did not (n=6) were compared. Also, the characteristics of patients with or without >5% LV ejection fraction (LVEF) decline during the follow-up period (n=5 vs. n=7) were compared. Thirteen patients (87%) had arrhythmias, and eight patients (53%) had LV wall motion abnormalities. Although arrhythmias decreased after treatment, reduced LVEF and LV wall motion abnormalities persisted. Further investigation revealed an increased LV end-systolic dimension and reduced LVEF in patients without additional immunosuppressive therapy, while those in patients with additional immunosuppressive therapy were maintained. Six of seven patients (86%) without LVEF decline received additional immunosuppressive therapy, whereas no patients with LVEF decline had additional immunosuppressive therapy. Cardiac involvement in AMA-positive myositis may worsen even with glucocorticoid monotherapy, and there might be some associations between the change of LV function and additional immunosuppressive therapy.

Clinical features of anti-mitochondrial M2 antibody-positive myositis: case series of 17 patients

ObjectiveIn 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. MethodsThis study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. ResultsOf the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. ConclusionsThis study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.

P067 Covid- 19 infection as a trigger for immune inflammatory myositis

Abstract Background/Aims Increasing experience in managing patients with COVID-19 infection has demonstrated the development of autoimmune phenomena following infection. We describe a patient with preceding COVID-19 infection who presented with inflammatory immune myositis, positive myositis antibodies and a normal creatine kinase. Methods N/A Results A 61-year-old Caucasian female presented feeling generally unwell and with weakness. She had COVID-19 infection 4 months prior, which necessitated admission to the Intensive Care Unit (ITU), treatment with dexamethasone and oxygen and subsequent discharge with home continuous positive airway pressure (CPAP). Other co-morbidities included atrial fibrillation, chronic kidney disease stage three, hypertension, obesity, recent pulmonary embolism, obstructive sleep apnoea, chronic lymphoedema and hypercholesterolaemia on atorvastatin. Her mobility had been gradually reducing over the previous months to now requiring a wheelchair. Neurological examination demonstrated bilateral proximal lower limb weakness, power 3/5 and an unsafe swallow, for which a naso-gastric tube was inserted. A non-specific erythematous pruritic rash was noted on the arms. Full body Computerised tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain and spine were unremarkable. Creatinine kinase (CK) was within normal limits at 81, and C-reactive protein (CRP) was mildly raised at 36. C3 was low at 0.67 and C4 low at 0.03. Cryoglobulins were not detected. She was positive for antinuclear antibody (ANA) (1:320 titre), Ro-52, PM-Scl75, and anti-La. Anti-dsDNA was negative. Electromyography could not be performed due to the presence of chronic lymphoedema. MRI showed symmetrical STIR hyperintense signal changes in the quadriceps muscles bilaterally. A muscle biopsy showed a small focus of mild lymphocyte infiltration in the endomysial connective tissue, mild increase in acid phosphatase expression in many fibres in dotlike pattern, overexpression of HLA-ABC with deposits of complement found in in endomysial capillaries, consistent with a diagnosis of inflammatory myopathy. Following commenced of 60 mg prednisolone daily, there was a marked improvement in swallowing and the NG tube was removed. A positron emission tomography (PET) scan showed non-specific marrow, splenic and adrenal hyperplasia. The patient was then started on mycophenolate mofetil (MMF), but was switched to azathioprine due to side effects. On review following discharge, the patient continues to require a wheelchair to mobilise, but there has been improvement in her swallow and she reports feeling better within herself. Conclusion Inflammatory myositis is a rare sequela of COVID-19 infection. The development of myositis-specific antibodies post infection has previously been described. This case highlights the significant dysphagia and debility despite a normal CK and the need for a high index of suspicion. Possible triggers of an inflammatory response predisposing to autoimmune phenomena include molecular mimicry, bystander activation, exposure of previously hidden epitopes to activated T cells, activation of Toll-like receptors and activation of the complement system. Disclosure G. Bartminski: None. A. Vijayan: None. K. Beharry: None. D. De Lord: None.

Clinical Profile of Anti-Transcription Intermediary Factor-1 Gamma-Positive Adults from a Single Tertiary Care Center

Anti-transcription intermediary factor-1 γ (TIF-1 γ) antibody is a myositis-specific antibody. These cases had specific clinical features in the past studies. There is no published data on such patients from South Asia. We retrospectively looked at data from patients with positive anti-TIF-1 γ antibodies from our hospital database between May 2019 and October 2020. Their clinical presentation, muscle and extra muscular involvement, investigations, presence of malignancy, and treatment with subsequent follow-up were retrieved using the electronic medical records. TIF-1 γ was rare at our center and was 2.46% out of the total positive myositis immunoblot results. Seven adult patients had significant anti-TIF-1 γ positivity. Five out of them had clinical muscle weakness; none had severe or respiratory muscle weakness. No patients had cancer-associated myositis. The skin was the most common extra muscular organ involved. The absence of cancer-associated myositis with anti-TIF-1 γ subjects in our series may represent the difference in phenotype in the South Asian population.

Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria for Idiopathic Inflammatory Myopathies in Patients With Myositis-Specific Autoantibodies.

We undertook this study to 1) determine the sensitivity of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) to properly classify myositis-specific autoantibody (MSA)-positive myositis patients, 2) describe the phenotype and muscle involvement over time in different MSA-positive patients, and 3) compare MSA subgroups to EULAR/ACR criteria-defined myositis subgroups for their capacity to predict clinical phenotypes in patients with IIMs. The study included 524 MSA-positive myositis patients from the Johns Hopkins Myositis Center. Each patient was classified using the EULAR/ACR classification criteria. Patient phenotypes were summarized using factor analysis of mixed data (FAMD). We compared the ability of MSAs to that of the EULAR/ACR classification subgroups to predict the phenotype of patients by applying the Akaike information criterion (AIC) and the Bayesian information criteria (BIC) to the linear regression models. Overall, 91% of MSA-positive patients met the EULAR/ACR criteria to be classified as having myositis. However, 20% of patients with anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) and 50% of patients with anti-PL-7 were incorrectly classified as not having myositis. Furthermore, ~10% of patients with anti-signal recognition particle (anti-SRP) and patients with anti-HMGCR were misclassified as having inclusion body myositis. FAMD demonstrated that patients within each MSA-defined subgroup had similar phenotypes. Application of both the AIC and BIC to the linear regression models revealed that MSAs were better predictors of myositis phenotypes than the subgroups defined by the EULAR/ACR criteria. Although the EULAR/ACR criteria successfully classified 91% of MSA-positive myositis patients, certain MSA-defined subgroups, including those with autoantibodies against HMGCR, SRP, and PL-7, are frequently misclassified. In myositis patients with MSAs, autoantibodies outperform the EULAR/ACR-defined myositis subgroups in predicting the clinical phenotypes of patients. These findings underscore the need to include MSAs in a revised myositis classification scheme.

Clinical and therapeutic features of myositis associated with anti-MDA5 antibodies: three new cases

Abstract Purpose To assess clinical features, therapy, and outcome of the myositis associated with anti-MDA5 antibodies, and to propose a successful therapeutic protocol for rapidly progressive interstitial lung disease (RP-ILD) in anti-MDA5 dermatomyositis (DM). Methods A retrospective and descriptive study of three cases of anti-MDA5 associated myositis was conducted in the Department of Internal Medicine in the University Hospital Hedi Chaker, Sfax, Tunisia, between 1996 and 2016. Results From a series of 115 cases of myositis, three cases of anti-MDA5-positive DM were identified. They were three men with a mean age of 63 years. They manifested specific cutaneous manifestations including ulcers and palmar papules, mild muscular involvement, and RP-ILD. The severity of the disease was correlated to the ILD in all patients. Aggressive therapies were tried including high-dose corticoids, cyclophosphamide (CYC) cures, intravenous immunoglobulins, and rituximab (RTX), with a good outcome in the patient who received combined high steroids, CYC, and RTX pulses. The two other patients died because of a rapid worsening of their respiratory condition. Conclusion Anti-MDA positive myositis is characterised by a specific cutaneous phenotype, the discretion of muscular signs, and the correlation with RP-ILD. The poor prognosis of this entity is correlated to the high resistance of pulmonary involvement despite aggressive therapeutics. The combination between high-dose steroids, CYC, and RTX has shown good results in many reports, as well as in one of our patients.

Association of extended myositis panel results, clinical features, and diagnoses: a single-center retrospective observational study

Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) are a feature of the idiopathic inflammatory myopathies (IIM), but are also seen in other rheumatic diseases, and in individuals with no clinical symptoms. The aim of this study was to assess the clinical utility of MSA and MAA and in particular the clinical relevance of weakly positive results. We included all patients at our institution who had at least one positive result on the Immunoblot EUROLINE myositis panel over a 6-year period (2015–2020). Associations with clinical features and final diagnosis were evaluated. Eighty-seven of 225 (39%) myositis panel tests met the inclusion criteria. There were 52 strong positives and 35 weak positives for one or more MSA/MAAs. Among the strong positive group, 15% (8/52) were diagnosed with IIM, 34.6% (18/52) with interstitial lung disease, 7.7% (4/52) with anti-synthetase syndrome, 25% (13/52) with connective tissue disease, and others accounted for 25% (13/52). In weak-positive cases, only 14% (5/35) had connective tissue disease and none had IIM. 60% (21/35) of weak-positive cases were not associated with a specific rheumatic disease. A significant number of positive myositis panel results, particularly weak positives, are not associated with IIM or CTD.

The phenotype of myositis patients with anti-Ku autoantibodies

ObjectivesTo define the clinical features of anti-Ku-positive myositis patients and to determine the reliability of the Euroline assay to detect anti-Ku autoantibodies. MethodsSerum samples were screened for anti-Ku autoantibodies by Euroline and positive samples were confirmed by ELISA. The prevalence and severity of clinical features at onset and during follow-up in patients with anti-Ku-positive myositis were compared to those with dermatomyositis, immune-mediated necrotizing myopathy (IMNM), the antisynthetase syndrome (AS), inclusion body myositis (IBM), anti-U1-RNP-positive myositis, and anti-PM/Scl-positive myositis. Results72 (2.9%) of 2475 samples were anti-Ku positive by Euroline using the manufacturer's recommended cutoff of >15. Just 17 (23.6%) of these were confirmed by ELISA and considered anti-Ku-positive for the analysis. Comparators included 169 IMNM, 168 AS, 387 IBM, 20 anti-U1-RNP-positive, and 47 anti-PM/Scl-positive patients. Muscle weakness was a presenting feature in 38% of anti-Ku-positive patients; 81% developed weakness during follow-up. Anti-Ku-positive patients had increased distal weakness compared to the non-IBM comparators. Interstitial lung disease (ILD) was present in 19% of anti-Ku-positive patients at the first visit and eventually developed in 56% of them. Throughout the course of disease, Gottron's papules and/or heliotrope rashes were less common in anti-Ku-positive patients (19%) compared to those with dermatomyositis (94%) or anti-PM/Scl-positive myositis (89%). Anti-Ku-positive patients never developed calcinosis. ConclusionsThe phenotype of anti-Ku positive myositis is distinguished by distal weakness, frequent ILD, infrequent rash, and no calcinosis. When used according to the current manufacturer's instructions, the Euroline assay has a high false-positive rate for anti-Ku autoantibodies.

P153 Characteristics of anti-melanoma differentiation-associated gene 5 positive dermatomyositis in Singapore

Abstract Background/Aims Anti-melanoma differentiation-associated gene 5 (MDA5) Ab positive associated dermatomyositis (DM) patients with rapidly progressive-interstitial lung disease (RP-ILD) have poor survival rates. The aim of this study was to determine the various characteristics in Singaporean patients with anti-MDA5-Ab associated DM. Methods A chart review was undertaken of 84 DM patients with positive myositis specific antibodies, diagnosed between January 2015 to July 2019, at a major tertiary centre in Singapore. All had confirmed probable or definite DM according to the Bohan and Peter criteria, and only those with an International Myositis Classification Criteria score of at least 55% (probable idiopathic inflammatory DM) were included. Results 18 out of 84 were anti-MDA5-Ab positive (See Table 1 for summary). Features more common in the anti-MDA5 Ab positive vs. the anti-MDA5 Ab negative cohort included: inverse Gottron’s papules (27.8% vs. 3%, p = 0.001) palmar papules (27.8% vs. 0%, p < 0.001), violaceous rash (55.6% vs. 16.7%, p = 0.001), cutaneous ulcers (66.7% vs. 6.1%, p = <0.001), clinically amyopathic DM (50% vs. 22.7%, p = 0.023) and polyarthritis (38.9% vs. 12.1%, p = 0.0009). The anti-MDA5 Ab positive cohort had a lower median creatine kinase (IU/L) versus the anti-MDA5 Ab negative cohort; 328 [60-3254] vs. 1318 [61-36776], (p = 0.0027). ILD was more common in the anti MDA5 Ab positive vs. anti-MDA5 Ab negative cohort (61.1% vs. 34.8%; p = 0.044). Of these anti-MDA5 Ab positive with ILD, 45.5% had RP-ILD, 27.3% had either chronic ILD or asymptomatic ILD respectively. In contrast, only 17.4% had RP-ILD in the anti-MDA5 Ab negative cohort. The mortality rate in the anti-MDA5 Ab positive vs. negative cohort was higher (33.3% vs. 24.2%). Patients with both Ro-52 and MDA5 Ab positivity had a higher incidence of cutaneous ulcers, pneumothorax, ILD and mortality. Of those anti-MDA5-Ab positive cases that survived, treatment included either rituximab and/or tofacitinib. Conclusion In our population, anti-MDA5 Abs associated DM is a distinct clinical subset of DM and associated with increased mortality. Better recognition of these distinct clinical features will enable early diagnosis, risk stratification and aggressive treatment to improve survival. Disclosure J. Low: None. C. Chua: None. W. Lim: None. L. Koh: None. M. Manghani: None.

Real world utilization of the myositis autoantibody panel.

Myositis autoantibody panel results can offer diagnostic and prognostic information in patients with concern for idiopathic inflammatory myopathy (IIM). However, there has been widespread utilization of myositis autoantibody testing clinically, often in situations where concern for an IIM is unclear. We sought to determine ordering practices and factors predicting positive results on ordered myositis antibody panels. We included all patients in the Duke University Health System who had a "myositis antibody panel" ordered from October 2014 through December 2016. Retrospective chart review was performed evaluating antibody positivity, provider specialty, ordering location, demographics, medical history, review of systems (ROS), physical examination (PE), and laboratory values. Fisher's exact and t test tests and backward multivariable regression analysis were performed for statistical analysis. There were 642 unique tests obtained with 114 positive autoantibodies (17.7%) over the 26-month period. Myositis-specific autoantibodies (MSAs) were the most common and anti-Mi-2 was the most frequent (40% of MSAs). Pulmonology providers ordered the majority of tests (383; 59.6%). Adult Rheumatology had the highest antibody positivity rate (34.3%, p=0.0001) among specialties with at least 10 panels ordered. In backward multivariable regression analysis, factors independently associated with a positive myositis antibody panel were chronic corticosteroid use (OR: 2.10, 95% CI: 1.30-3.38) and sclerodermoid skin changes (OR: 6.89; 95% CI: 2.02-23.47). The positivity rate of myositis antibody panel testing in this real-world clinical setting was 18%. Anti-Mi-2 antibody was the most frequent autoantibody present. Specific factors associated with positive results can be utilized to identify patients at higher risk for IIM. • Only eighteen percent of all myositis antibody panel tests ordered returned positive. • Anti-Mi-2 antibody was the most frequent autoantibody in our cohort. • Specific factors associated with positive results can help identify patients at higher risk for IIM, particularly for non-rheumatologists.

The analysis of clinical phenotypes and autoantibodies in juvenile dermatomyositis

Objective: To elucidate the relationship between the myositis autoantibodies and clinical phenotypes of juvenile dermatomyositis (JDM). Methods: A total of 76 JDM patients admitted to the Children's Hospital of Chongqing Medical University from January 2017 to May 2020 were tested for myositis autoantibodies, including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). Kruskal-Wallis test and logistic regression were used to analyze the relationship between the antibodies and clinical characteristics. Results: In the 76 cases, 37 were females and 39 males. Forty-three cases (53%) were MSAs positive, among which the most common subtypes were autoantibodies against nuclear matrix protein 2 (NXP2) (15/76, 20%), melanoma differentiation-associated protein 5 (MDA5) (13/76, 17%) and transcription intermediary factor 1 gamma (9/76, 11%). While 20 cases (26%) were positive for MAAs, among which anti-Ro-52 antibody (17/76, 22%) was the most common subtype. Sixteen patients (21%) had both MAAs and MSAs. The incidences of arthritis (9 cases), fever (8 cases), skin ulcers (5 cases) and macrophage activation syndrome (MAS) (1 case) were significantly higher in the patients with anti-MDA5 antibody among the antibody groups. Dysphasia (6 cases) and edema (8 cases) mainly occurred in patients with anti-NXP2 antibody. Children with anti-MDA5 antibody were more likely to develop arthritis (OR=10.636, 95%CI: 2.770-40.844, P=0.001), skin ulcers (OR=12.500, 95%CI: 2.498-62.522, P=0.002), fever (OR=5.600, 95%CI: 1.580-19.849, P=0.008) and interstitial lung disease (ILD) (OR=23.333, 95%CI: 4.750-114.616, P<0.01). In the patients with different subtypes of MSAs, the creatine kinase value was significantly lower in the anti-MDA5 group than those in the anti-aminoacyl-tRNA synthetase (P=0.03), anti-NXP2 (P<0.01), and MSAs-negative group (P=0.013). Conclusions: Most children with JDM have positive myositis autoantibodies, and will present with different clinical phenotypes based on different autoantibodies. And children with anti-MDA5 antibodies are likely to develop ILD and MAS. Therefore the detection of myositis-specific autoantibodies is important.

Effectivness and safety of exercise in idiopathic inflammatory myopathies – case report and review of the literature

Idiopathic inflammatory myopathies (IIM) are rare systemic autoimmune diseases characterized by proximal muscle weakness, evidence of muscle inflammation and damage and other extramuscular organ involvement, especially lungs.Early diagnosis and initiation of treatment reduces muscle inflammation and lowers the chance of developing extramuscular disease and muscle damage. Glucocorticoids are the cornerstone of pharmacological treatment, they are used in combination with immunosuppressive and immunomodulatory medications. Clinical and serological subtypes of IIM are very diverse, and they respond differently to pharmacological treatment. Therapeutic exercise in addition to medicaments is an important adjunct for the treatment of IIM. Improvement in muscle strength, impairment reduction, anti-inflammatory activity and increased metabolism in muscle fibers are all proven effects of exercise in many scientific studies.Exercise is a safe and effective treatment in both chronic and acute stage of myositis. Rehabilitation program should be individually adapted to every patient, and validated instruments should be used to measure clinically important change.In this paper we present a 3-year clinical course of a patient diagnozed with an anti-SRP positive myositis with a special review of stationary rehabilitation in the acute stage of the disease. Review of the literature is presented in discussion.