Group Of Idiopathic Inflammatory Myopathies Research Articles

Fibroblast activation protein inhibitor positron emission tomography imaging in muscles of patients with idiopathic inflammatory myopathy.

Mesenchymal stromal cells in muscles participate in regeneration following muscle injury. This study explored the potential of [18F]fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography (PET) targeting mesenchymal stromal cells to evaluate disease activity of idiopathic inflammatory myopathy (IIM). Patients with IIM (n = 26) were prospectively included and underwent [18F]FAPI-42 PET/CT and whole-body MRI between January 2023 and July 2023. Patients with malignancies were retrospectively included in the control group and only underwent [18F]FAPI-42 PET/CT (n = 28). [18F]FAPI-42 PET/CT images were evaluated using for avid-FAPI uptake and the target-to-background ratio (TBR). Whole-body MRI was evaluated for oedema, fatty infiltration, and atrophy in 42 muscles in the IIM group. The global FAPI- and MRI-derived parameters were calculated for each. . Clinical assessment of disease activity and muscle strength were collected. Patients with IIM had significantly higher global FAPI-avid muscle ratios (0.68 [interquartile range (IQR): 0.45, 0.79] vs 0.06 [IQR: 0, 0.11], p< 0.001) and global muscle TBR (2.26 [IQR: 1.71, 2.75] vs 1.23 [IQR: 1.02, 1.52], p< 0.001) compared with controls. In the IIM group, the median TBR was higher in muscles with oedema than in those without (2.44 [IQR: 1.46, 3.27] vs 1.31 [IQR: 0.95, 1.99], p< 0.001). Global FAPI-avid muscle ratios significantly correlated with global oedema score (r = 0.833), muscle strength (r=-0.649), serum creatine kinase (r = 0.456), and disease activity index (r = 0.495-0.621). Increased [18F]FAPI-42 uptake was associated with muscle oedema in IIM. FAPI-derived parameters correlated with IIM disease activity. [18F]FAPI-42 is a promising PET tracer for evaluating IIM disease activity.

Association of anti-Ro-52 antibodies with occurrence of interstitial lung disease in patients with idiopathic inflammatory myopathy

BackgroundAnti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs.MethodsThis retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth’s logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories.ResultsThis study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold.ConclusionsAmong patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.

Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies

BackgroundTo develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features.MethodsMuscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs.ResultsIn the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician.ConclusionsCombination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.

Spirituality, Religiosity, and Mental Health in Patients with Idiopathic Inflammatory Myopathies: A Brazilian Multicentric Case-Control Study.

No published studies have investigated the correlation between religiosity, spirituality, mental health, and idiopathic inflammatory myopathy (IIM) or systemic autoimmune myopathy. Therefore, we aimed to evaluate the association between religiosity/spirituality, sociodemographic factors, and the mental health of IIM patients. This is a multicenter case-control study that included 151 patients with IIMs and 95 individuals without autoimmune diseases (controls), held between August 2022 and April 2023. This study used a semi-structured questionnaire that included sociodemographic information and the juxtaposition of the following questionnaires: the Attitudes Related to Spirituality Scale (ARES); the Duke University Religion Index (DUKE), which is composed of the organizational religious affiliation (ORA), non-organizational religious affiliation (NORA), and intrinsic religiosity (IR) domains; and the General Health Questionnaire-12 (GHQ-12). Data were analyzed using Epi Info software 7.2.5 (Centers for Disease Control and Prevention, Atlanta, GA, USA). A comparison between the mean values of the ARES, DUKE, and GHQ-12 scales was made using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. A logistic regression test was used with the variables whose difference was statistically significant in the univariate analysis. Correlation analysis was performed using the Spearman rho coefficient. A higher prevalence of evangelicals and a lower prevalence of Catholics (p < 0.050) were seen in the IIM group compared to controls. Positive association was demonstrated between IIMs and the pardo ethnicity (OR = 2.26, 95% CI = 1.20-4.25, p = 0.011), highest ORA (OR = 2.81, 95% CI = 1.53-5.15, p < 0.001), NORA (OR = 3.99, 95% CI = 1.94-8·18, p < 0.001), IR (OR = 5.27, 95% CI = 2.32-11.97, p < 0.001), and ARES values (OR = 1.08, 95% CI = 1.04-1.13, p < 0.001). Mental health levels were compared between the groups (p > 0.999). Therefore, higher levels of religiosity and spirituality were observed in the IIM group than in the control group, but there was a similar distribution of mental health levels. The following can be cited as advantages of the present study: (i) the large sample for a rare disease with the presence of a control group; (ii) the multicenter characteristic with participation from three regions of Brazil; (iii) being the first study to map aspects of religiosity, spirituality, and mental health in IIMs.

Magnetic resonance imaging scoring system of the lower limbs in adult patients with suspected idiopathic inflammatory myopathy

PurposeWe aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM).Material and methodsWe retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible.ResultsOf the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%.ConclusionOur study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it.

Antisynthetase syndrome: a case report and review of the literature.

antisynthetase syndrome is a rare autoimmune disease characterized byinterstitial lung disease, non-erosive arthritis, myositis, Raynaud&amp;#39;s disease, and/or &amp;quot;mechanichand&amp;quot; when autoantibodies directed against aminoacyl-tRNA synthetases are detected.Antisynthetase syndrome belongs to the group of idiopathic inflammatory myopathies and isthe so-called overlap myositis. The article provides the latest literature data on the diagnosticvalue of myositis-specific autoantibodies based on a literature review for the period from2013 to 2023 using the scientometric databases MEDLINE/ PubMed, Wiley Online Library,and Scopus. Data from the literature show that certain myositis-specific autoantibodies,namely anti-PL-7 and anti-PL-12, can affect the risk of developing interstitial lung disease,and determine the course and prognosis of the disease. The presence of interstitial lungdisease in patients with myositis correlates with increased morbidity and mortality. Thearticle describes a clinical case of the debut of the antisynthetase syndrome from interstitiallung disease, which was falsely diagnosed as a coronavirus disease. The patient&amp;#39;s condition&#x0D; improved only because of using glucocorticoids, which the patient stopped taking over time,which led to the worsening of pulmonary symptoms, the appearance of new clinical signs ofdamage to the joints and skin, progressive decrease in muscle function, and dysphagia. Afteran examination in the rheumatology department, based on the presence of interstitial lungdisease in the patient - fibrotic alveolitis, which was confirmed by computer tomography,myositis, arthritis, characteristic skin changes, the presence of antinuclear antibodies, anti-SS-A/Ro52, specific antisynthetase antibodies (Jo-1, Pl-7, Pl-12), the diagnosis of theantisynthetase syndrome was established. A detailed laboratory and instrumental examinationmade it possible to rule out a paraneoplastic process at the time of examination. Theprescribed treatment included pulse therapy with methylprednisolone and cyclophosphamide,which led to improvement in the patient&amp;#39;s condition. The work carried out emphasizes theneed for interdisciplinary interaction of pulmonologists, rheumatologists, and infectiousdisease specialists at the stage of verification of the final diagnosis and the therapyappointment. Achieving clinical and laboratory remission of the disease requires long-termmonitoring by a rheumatologist.

The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy.

N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles, however, its value in patients with IIM is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage. Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P<0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P<0.001). the N-titin level was strongly correlated with CK (r = 0.907, P<0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio=1.035, 95% CI: 1.002, 1.069, P=0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC=0.971, 95% CI: 0.938, 1.000, P<0.001). Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.

Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance.

Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40-70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies.

Reduced bone mineral density in patients with idiopathic inflammatory myopathies: a case-control study.

Patients with idiopathic inflammatory myopathies (IIMs) are at risk of reduced bone mineral density (BMD). To compare the prevalence of reduced BMD between patients with IIMs and controls and to determine its risk factors. This was a single-center case-control study. BMD was assessed by dual-energy X-ray absorptiometry. The prevalence of reduced BMD in IIM patients and age-and sex-matched non-rheumatological controls was compared. The BMD results of female IIM were also compared to age-matched female rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Independent factors associated with reduced BMD in IIM patients were identified by multivariate analyses. A total of 230 patients (IIM: 65, non-rheumatological controls: 65, RA: 50, SLE: 50) were recruited. The mean age of IIM patients was 58.6 ± 11.0 years and 76.9% were females. Significantly, more IIM patients had reduced BMD (73.8% versus 43.1%, p = 0.043) and osteoporosis (29.2% versus 13.8%, p = 0.033) than non-rheumatological controls. Multivariate analysis confirmed that IIM was independently associated with reduced BMD (OR: 2.12, p = 0.048, 95% CI: 1.01-4.46). The prevalence of reduced BMD was not significantly different between IIM, RA, and SLE patients but the mean hip BMD was the lowest in the IIM group (0.641 ± 0.152 g/cm2versus 0.663 ± 0.102g/cm2 in the RA group versus 0.708 ± 0.132 g/cm2 in the SLE group, p = 0.035). Lower body mass index and more advanced age were independently associated with lower BMD in IIM patients. Reduced BMD was more prevalent in IIM patients than in non-rheumatological controls. Hip BMD was lower in patients with IIMs than RA or SLE. Close monitoring and early treatment are encouraged especially in patients with risk factors.

Genetic Influences in Cancer-Associated Myositis.

Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.

Inclusion body myositis: from genetics to clinical trials

Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies and is characterized by a slowly progressive disease course with asymmetric muscle weakness of predominantly the finger flexors and knee extensors. The disease leads to severe disability and most patients lose ambulation due to lack of curative or disease-modifying treatment options. Despite some genes reported to be associated with hereditary IBM (a distinct group of conditions), data on the genetic susceptibility of sporadic IBM are very limited. This review gives an overview of the disease and focuses on the current genetic knowledge and potential therapeutic implications.

Диагностика и лечение статин-индуцированной некротизирующей аутоиммунной миопатии

Statin-induced necrotizing autoimmune myopathy (SINAM) is an exceptionally rare complication of statin therapy. SINAM belongs to the group of idiopathic inflammatory myopathies and is characterized by muscle cell necrosis and regeneration leading to muscle atrophy. Prominent lymphocytic infiltrates in muscle tissue are absent. Progressive muscle weakness in upper and lower extremities is the main clinical manifestation of SINAM. Autoimmune mechanism of pathogenesis explain the absense of therapeutic effect of statin discontinuation and the risk of relapses. Diagnosis of SINAM can be established by clinical and serologic data, muscle biopsy and the results on noninvasive methods (MRI, ultrasound). Early initiation of immunosuppressive treatment is essential to achieve the cure of SINAM.

P070 Patients with idiopathic inflammatory myopathies suffer from poor self-reported PROMIS physical function after COVID-19 infection: an interview-based study from the MyoCite cohort

Abstract Background/Aims Patients with rheumatic diseases are known to exhibit worse outcomes with COVID-19. However, the effect on individual diseases such as idiopathic inflammatory myopathies (IIM) remain unexplored. Methods A self-report e-survey with 36 questions was pilot tested and validated to cover demographics, history of COVID-19 contact, course and severity of COVID-19 infection, influence of COVID-19 infection on physical state one-month after the infection and vaccination status. Baseline characteristics were retrieved from the MyoCite registry and biobank archive. PROMIS-10a, a validated self-report tool was used to quantify physical function. Age and gender similar healthy controls (HC) were included for comparison. Results 10 patients of IIM were compared with 40 controls. Fever was the most common symptom reported by both the groups however, fatigue, chest pain, and breathlessness were experienced more by patients of IIM compared to HC. However, severity of COVID-19 infection as substantiated by pneumonia, hospitalization, and oxygen requirement was comparable in IIM and HC, possibly due to small numbers PROMIS physical function was comparable before COVID-19 in both groups, and in HC physical function remained the same a month before and after COVID-19. On the other hand, the physical function deteriorated at 30-days after COVID-19 in the IIM group as compared with their baseline function as well as HC. Specific tasks were more challenging for IIM, including climbing stairs, bending or kneeling and shampooing hair, although the limitation was mild (Table 1). IIM patients were also less likely to be vaccinated, suggesting prevalent hesitancy in this group (50% vs 90%, p: 0.007) (Table 1). Conclusion Patients with IIM exhibit increase in fatigue, and dyspnoea during COVID-19 although there is no increase in hospitalisation and had similar disease severity compared to HC. Short term physical function is impacted at 30-days post COVID-19, suggesting the need for closer long-term follow-up. Vaccine hesitancy is prevalent and merits addressing in patients with IIM. Disclosure R. Kharbanda: None. K. Ganatra: None. V. Agarwal: None. L. Gupta: None.

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study.

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p < 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p < 0.05).Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.

Radiologic examination of pharynx for oropharyngeal dysphagia in a patient with dermatomyositis (clinical observation)

Dermatomyositis – a systemic connective tissue disease, from the group of idiopathic inflammatory myopathies. Affection of the skeletal muscle tissue in inflammatory myopathies causes progressive muscle weakness. In dermatomyositis reduction in contraction ability of the muscles involved in the act of swallowing, leads to violation of the mechanism of respiratory protection from getting food masses inside and from development of dysphagia.The purpose of the study was to evaluate the changes detected in the process of radiologic examination of the dermatomyositis patient’s throat.Materials and methods. Patient K. 61 years old, he has dermatomyositis and clinical signs of oropharyngeal dysphagia. The patient underwent a pharyngeal radiologic examination, which allowed to confirm the disturbance of swallowing function and to establish the fact of aspiration.Results and discussion. Radiological examination of the pharynx showed signs of pharynx hypotony, pharyngeal ectasia, stasis, residual amount of radiocontrast agent in caudal section of larynx, penetration, aspiration.Conclusion. Radiological examination of the pharynx in patients with dermatomyositis is important method examination of studying swallowing disorders and predicting risk of serve complications.The peculiarity of this case is the demonstration of swallowing dysfunction dynamics in a patient with dermatomyositis at admission to the clinic and after treatment.

DYSPNEA UNVEILED BY HANDS: A CHALLENGING CASE OF RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antisynthetase syndrome (ASS) is a rare autoimmune condition characterized by antibodies directed against amino-acyl-tRNA synthetase along with clinical features of myositis, arthritis, Raynaud’s phenomenon and interstitial lung disease (ILD). We present a case of rapidly progressive ASS associated ILD. CASE PRESENTATION: A 40-year-old African American woman with past medical history of smoking and prior hospitalization for presumed pneumonia presented to the emergency department with complaints of ongoing but worsening cough and dyspnea for more than four months. She was hypoxic and lung examination revealed bilateral fine crackles. Chest imaging revealed patchy mixed consolidation and ground-glass opacities at the lung bases (figure 1). Her course worsened needing mechanical ventilation. Given the clinical picture and imaging findings raising concerns for ILD, she underwent VATS/lung biopsy, which revealed pinkish fibrous plugs: Masson bodies, concerning for organizing pneumonia (figure 2). Autoimmune work including ANA and rheumatoid factor was negative. She continued to decline despite broad-spectrum antibiotics and high dose steroids and had to be placed on VV-ECMO for severe ARDS. Hyperkeratosis and hyperpigmentation of her hands were later noted, raising concerns for an autoimmune process. A myositis panel was done, which revealed positive Anti-PL12 antibodies. Lung function recovery was sub-optimal despite ECMO support for 85 days, IVIG, plasma exchange and cyclophosphamide therapy. She had to undergo single left lung transplantation. She eventually was discharged home on immunosuppressants after five months of hospitalization. Her explanted lung showed features of non-specific interstitial pneumonia. She has done well for more than 2 years post-transplant with amelioration in the imaging findings of her native right lung and with no signs of graft rejection. The final diagnosis was rapidly progressive ASS associated ILD with progression to ARDS requiring single lung transplantation. DISCUSSION: ASS is a rare group of idiopathic inflammatory myopathies, characterized by the presence of seven different myositis-specific antisynthetase antibodies with Anti-Jo1 being the most common one. Anti-PL12 antibody type is associated with a severe form of ILD. ANA antibodies are typically negative and hence a high index of suspicion for ASS is warranted. Literature about the management of ASS-ILD is sparse but anecdotal experience favors steroids as first-choice agents and other immunosuppressive agents, plasma exchange therapy, and even lung transplantation in severe and refractory cases. CONCLUSIONS: Our case of ASS-ILD with anti-PL12 antibodies shows the rapid progression of the ILD despite aggressive immunosuppressive therapy and highlights the importance of identification, aggressive therapy and the role of VV-ECMO with lung transplantation as an option for refractory cases. Reference #1: Connors GR, Christopher-Stine L, Oddis CV, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464–1474. Reference #2: Esposito AC, Gige TC, Miot HA. Syndrome in question: antisynthetase syndrome (anti-PL-7). An Bras Dermatol. 2016;91(5):683-685. DOI:10.1590/abd1806-4841.20164449 Reference #3: Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. DOI:10.1097/CPM.0000000000000171 DISCLOSURES: No relevant relationships by Anas Alameh, source=Web Response No relevant relationships by Ansaam Daoud, source=Web Response No relevant relationships by Sujith Modugula, source=Web Response No relevant relationships by Lokesh Venkateshaiah, source=Web Response No relevant relationships by Elizabeth Verghese, source=Web Response

OMICs AND AI APPROACHES FOR MUSCLE DISEASES: O.08 Deep convolutional-neural-network can differentiate twelve major muscular diseases better than human

Muscle pathology plays an important role in the diagnosis of muscle disease even in the molecular era, as most muscle diseases have been classified or even partly defined by pathological features. Nevertheless, availability of experts is limited especially in underserved areas of the world. This study aims to establish the algorithm to assist muscle pathology diagnosis using deep convolutional neural networks (CNNs), which can differentiate major muscle diseases only by hematoxylin and eosin (H&E)-stained pathological images. Target diseases were dystrophinopathy (DYST), limb-girdle muscular dystrophy (LGMD) 2A (LG2A), LGMD2B (LG2B), Ullrich congenital muscular dystrophy (CMD) (UCMD), Fukuyama CMD (FCMD), congenital myopathy (CM), GNE myopathy (GNEM), dermatomyositis (DM), inclusion body myositis (IBM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and neuropathic disease (NP). All images to train CNNs were taken from slides with CCD cameras via light microscopes. A total of 4041 images were obtained from 1400 slides. The algorithm consists of two steps: 1) to differentiate between idiopathic inflammatory myopathy (IIM) and other conditions, and 2) to subclassify each category. For the first step, images of DM, IBM, IMNM, and ASS were combined to create the IIM group. Meanwhile, those of DYST, FCMD, LG2A, LG2B, UCMD, CM, GNEM, and NP were combined to create another group. At the second step, four subtypes of IIM were analyzed. The first step achieved 0.996 area under the curve (AUC). The accuracy of the CNN and the best pathologist of all were 96.9% and 93.8%, respectively, indicating the CNN outperformed muscle specialists. In the second step, the CNNs classified four subtypes (DM, IBM, IMNM, and ASS) with high AUCs: 0.953 (IMNM), 0.969 (IBM), 0.965 (DM), and 0.944 (ASS). The algorithm used only a few H&E images obtained by CCD, which does not need a huge financial investment. This system should be helpful in clinical settings especially in underserved regions, where experts are not easily available.

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

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

An exploratory study of contractile force production in muscle fibers from patients with inflammatory myopathies.

The mechanism by which weakness develops in idiopathic inflammatory myopathies (IIMs) is still unclear. In this study we investigated the maximum force of single muscle fibers from patients with IIMs. Permeabilized single muscle fibers from patients with IIMs and healthy controls were subjected to contractility measurements. Maximum force and specific force production (maximum force normalized to fiber size) and fiber type were determined for each isolated fiber. A total of 178 fibers were studied from five patients with IIMs and 95 fibers from four controls. Specific force production was significantly lower in the IIM group for all fiber types. The findings from this exploratory study suggest that weakness in IIMs may, in part, be caused by dysfunction of the contractile apparatus. These findings provide a basis for further studies into the mechanisms underlying weakness in IIMs.

General Paresis in a Child with Unusual Presentation

Introduction: Acute onset quadriparesis can be a manifestation of a variety of neurological, metabolic or autoimmune conditions. Rarely, it could be one of many clinical presentations of juvenile dermatomyositis which belongs to the group of idiopathic inflammatory myopathies of childhood. We report the case of a 9-year old girl who presented with global myopathy over a two-month period. Case report: A 9-year-old girl referred with a 2 months history of generalised muscular pain and weakness. There were no significant history of preceded illness, trauma or excessive strenuous exercises. She had no other systemic complaints such as fever or skin rash. Past medical history was unremarkable except for recurrent tonsillitis. Physical examination revealed a child with normal alertness and behaviour. She has notable generalised swelling of all four limbs. Her neurological examination revealed normal tone however her power was definitely reduced in all four limbs (Graded 3/5). She demonstrated signs of proximal myopathy. Subsequent investigations revealed high Creatinine Kinase (CK) levels of 6470U/L, ESR 84mm/hr with deranged transaminases and positive serum mycoplasma and CMV IgM. Her MRI brain and spine along with lumbar puncture results were normal. She was referred to tertiary centre for further evaluation as her weakness progressed. An MRI muscle demonstrated marked inflammation in all four limbs including paravertebral muscles. Her muscle biopsy showed inflammatory myopathy leading to a diagnosis of juvenile dermatomyositis (JDM). She is now showing sustained clinical improvements following a course of immunoglobulin and corticosteroids therapy. Discussion: The diagnosis of JDM is generally considered in patients with rash-associated muscle weakness. Essentially, it involves assessment of muscle, skin, lung and cardiac involvement on top of baseline list of investigations that has been outline by Single Hub and Access point for pediatric Rheumatology in Europe (SHARE). This case reflects that JDM is possible despite non-existent of skin involvement.