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Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM–ILD–malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM–ILD–malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM–ILD–malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature. [ABSTRACT FROM AUTHOR]

Introduction/Aims: 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. Methods: This was a retrospective study of patients who underwent myositis antibody LB testing for suspected IIM between March 2019 and August 2022. Results: 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). Discussion: 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. [ABSTRACT FROM AUTHOR]

IntroductionIdiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort.MethodsPatients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features.ResultsSeventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected.Discussion:The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.

ObjectivesIdiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP.MethodsThis descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients’ medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia.ResultsA total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan–Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936–5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072–10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974–38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115–0.899, p = 0.031).ConclusionApproximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.

We accumulated the demographic information and analyzed the prevalence of myositis‐specific antibodies (MSAs) in a large cohort across Japan as standard testing for MSAs becomes more widely available. This retrospective, observational, cohort study analyzed the records of individuals aged 0–99 years who are tested for serum MSAs at SRL Incorporation from January 2014 to April 2020 across Japan. An enzyme‐linked immunosorbent assay testing was applied to determine the presence of anti‐aminoacyl tRNA synthetase (anti‐ARS), anti‐Mi‐2, anti‐melanoma differentiation‐associated gene 5 (anti‐MDA5), or anti‐transcriptional intermediary factor 1‐γ (anti‐TIF1γ) (Medical and Biological Laboratories). Anti‐TIF1γ antibody was detected more in male patients than female patients. In contrast, women were predominant in patients with other MSAs. More than half of the anti‐ARS or anti‐TIF1γ antibody‐positive patients were over 60 years old, although anti‐MDA5 or anti‐Mi‐2‐positive patients were mostly under <60 years old. Anti‐MDA5 antibody‐positive patients were mostly aged 40–59 years, while other MSA groups were mostly 60–79 years. Anti‐MDA5 antibody was detected most frequently in the age range of 0–29 years. Anti‐TIF1γ antibody was the second most commonly detected autoantibody in the age range of 0–19 years. Anti‐ARS antibody was the most frequently detected autoantibody after the age of 30 years, and the frequency of anti‐ARS gradually increased at more advanced ages. The second and third most detected autoantibodies were anti‐MDA5 and anti‐TIF1γ, respectively, in ages 30–79 years. We performed a nationwide >3‐year evaluation of MSA detection in a routine diagnostic setting. This paper provides clinical images concerning the relationship between four MSA types and the distribution of sex and age in a large population. [ABSTRACT FROM AUTHOR]

Calcinosis, or the deposition of insoluble calcium salts in the skin, subcutaneous tissue, fascia, tendons, and muscles, is a feared complication of juvenile dermatomyositis. Calcinosis is estimated to affect up to 40% of patients with juvenile dermatomyositis and contributes to significant disease morbidity. Calcinosis can be challenging to treat, and the most effective treatment remains unknown because of a lack of comparative studies. We aim to review the literature published in the last 5 years to summarize updates on the pathogenesis and treatment of calcinosis in juvenile dermatomyositis and describe future areas for research.

Background: Myositis‑specific autoantibodies (MSA) and myositis‑associated autoantibodies (MAA) are clinically useful biomarkers that point to the diagnosis, clinical manifestations, and prognosis of dermatomyositis (DM). Materials and Methods: To estimate the prevalence of MSA as well as MAA and analyze possible clinical correlations of these autoantibodies in patients diagnosed with DM, we conducted a cross‑sectional study of 30 patients who were diagnosed with DM. Results: MSA were positive in 19 patients (63%) in which Mi 2 was positive in 8 (27%) patients, and this was the most frequently found MSA. A total of 11 (36.7%) patients showed positive MAA. AntiPM/Scl 75 and anti‑Ro 52 were positive in 5 (16.7%) patients each and these were the most commonly found MAA. Anti‑La was absent in all our patients. There were 8 (27%) patients in whom both MSA and MAA were positive. Either MSA and/or MAA were positive in 22 (73%) patients. On a bivariate analysis, the patients who were positive for anti‑PM/Scl 75 showed a significant difference in manifesting cutaneous ulcers (P value 0.023). It was also found that anti‑SAE‑positive patients showed a significant difference with malignancy (P value 0.014). Anti‑Ro 52‑positive patients were less likely to have symmetrical proximal muscle weakness (P value 0.006). Conclusions: All patients who were anti‑MDA 5 positive had myositis and none of the anti‑MDA 5‑positive patients had rapidly progressive interstitial lung disease (RPILD). More than one MSA in the same patient was noted in three patients. [ABSTRACT FROM AUTHOR]

Objective Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. Methods Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. Results Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. Conclusions Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases characterized mainly by inflammation of muscle tissue. Although IIM traditionally encompasses polymyositis, dermatomyositis (DM), and inclusion body myositis, the disease concept has been changing in association with progress in diagnostic techniques. Thus, the new disease entities of amyopathic DM (ADM) or clinically ADM and immune-mediated necrotizing myopathy have been recognized recently. Because of the variety of symptoms or low prevalence or difficulty in correct evaluation of muscle strength and function in IIM patients, no standard treatment strategies have been established yet. Currently, glucocorticoids remain the first line of treatment of IIMs, but in addition to these, several other immunosuppressive agents or intravenous immunoglobulin have been used in a variety of different combinations. However, due to clinical heterogeneity of these conditions as well as the number of therapeutic target organs, IIM therapy remains challenging, and refractory cases are especially difficult to treat. In recent years, new therapeutic approaches using biologics or Janus kinase inhibitors, plasma exchange therapy, and other agents have been evaluated for IIMs. However, validation of the efficacy of these new treatment options remains an issue to be resolved. In this article, the author reviews current treatment strategies and new emerging therapies for IIM patients.

Objectives This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile. Methods A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included. Results MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n  = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n  = 25) and anti-nuclear matrix protein 2 (NXP2) (n  = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others. Conclusion Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to study and compare the clinical manifestations, auxiliary examinations, and therapeutic responses in patients with different myositis-specific antibody (MSA) types. Method: We retrospectively investigated the medical records of 143 hospitalized dermatomyositis patients, all of whom were tested for MSAs, and performed follow-up. Patients were divided into groups with and without anti-nuclear matrix protein 2 (NXP2) antibodies (17 vs 126 patients). Demographic, clinical manifestation (occurring at any time during the disease course), imaging, laboratory, treatment response, and survival data were collected for statistical analyses. Results: Adult dermatomyositis patients with anti-NXP2 antibodies were more prone to dysphagia (P<0.001), had higher levels of muscle injury markers (CK peak, P=0.007; CK peak>1000 IU/L, P<0.001; CK-MB, P=0.002), were younger at onset (P=0.008), and were less likely to present with interstitial lung disease (P=0.016) than the anti-NXP2 antibody-negative subgroup. Multivariable logistic regression analysis showed that onset age (OR=0.96 CI 95%: 0.924–0.999, P=0.043) and dysphagia (OR=7.088, CI 95%: 1.824–27.536, P=0.005) were independent risk factors for anti-NXP2 antibody positivity. Kaplan-Meier survival analysis did not reveal that dermatomyositis patients with anti-NXP2 antibodies have a relatively worse prognosis. However, the disease course was more frequently polycyclic, and 68.75% of patients had a relapsing-remitting disease course. More than half (52.94%) of those who showed no response to treatment used at least 3 disease-modifying antirheumatic drugs. Conclusions: We show the important clinical features of and risk factors for this unique antibody-mediated form of dermatomyositis. Although these patients had a relatively low mortality rate, they were prone to recurrence, and treatment was challenging. Key points • The clinical features and risk factors for adult dermatomyositis patients with anti-NXP2 antibodies. • The impact of anti-NXP2 antibody on survival outcomes. [ABSTRACT FROM AUTHOR]

Aim: To evaluate myositis line immunoassay (LIA) for diagnosis and sub‐classification of suspected idiopathic inflammatory myopathy (IIM). To investigate if test performance is improved by increasing signal strength cut‐off for myositis‐specific antibody (MSA) or combining MSA with indirect immunofluorescence (IIF). Methods: A retrospective, consecutive case series of patients investigated for MSAs from June 2013 to June 2020 for suspected IIM. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals for diagnosis of IIM. Association of IIM diagnosis with increased signal strength and presence of an expected IIF pattern on Hep‐2 cells was assessed by Fisher's exact test in MSA‐positive patients. Results: A total of 195 patients were evaluated. IIM was diagnosed in 32/195 (16.4%) patients. MSAs were detected in 41/195 (21%) patients, 18/41 (43.9%) patients with an MSA had a diagnosis of IIM. The probability of an IIM diagnosis was increased in MSA‐positive patients with high compared with low signal strength (83.3% vs 43.5%; P = 0.01) and an expected compared with unexpected IIF pattern (61.5% vs 23.8%; P = 0.04). Specificity for IIM was not significantly improved by increasing signal strength cut‐off (85.9% vs 93.8%). Positive predictive value of myositis LIA was only modest and not significantly improved by either increasing signal strength cut‐off or requiring an expected IIF pattern for determination of MSA positivity (43.9% vs 60% vs 61.5%). Sub‐classification of IIM correlated closely for respective MSAs (88.9%). Conclusion: Increased MSA signal strength on myositis LIA and the presence of an expected IIF pattern were associated with IIM diagnosis. Test performance was non‐significantly improved by these methods. Prevalence of IIM in this patient cohort was low; it is not excluded that LIA performance could be improved by these methods in a higher prevalence cohort. [ABSTRACT FROM AUTHOR]

Myositis-related interstitial lung disease presents with a wide variety of lesions, ranging from chronic to acute. It can be divided into two main forms by the types of onsets, namely, chronic to subacute type showing nonspecific interstitial pneumonia (NSIP) or NSIP with an organizing pneumonia (OP)/fibrosing OP (FOP) pattern and acute type showing acute lung injury (ALI) to diffuse alveolar damage (DAD) pattern. Anti-aminoacyl tRNA Synthetase antibody-positive cases mainly show an NSIP or FOP pattern, whereas anti-melanoma differentiation-associated gene 5 antibody-positive cases show ALI to DAD pattern. Bilateral consolidation with or without groundglass opacification with lower lobe predominance is common as a major pattern in all types, but the distribution or extent is sometimes different. The early detection of findings that indicate a rapid progressive course is vital. Diffuse cranio-caudal distribution and multiple ground-glass opacifications with random distribution might indicate a poorer prognosis. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is a systemic idiopathic inflammatory disease affecting skeletal muscle and skin, clinically characterized by symmetrical proximal muscle weakness and typical skin lesions. Recently, myositis‐specific autoantibodies (MSA) became of utmost importance because they strongly correlate with distinct clinical manifestations and prognosis. Antibodies against transcription intermediary factor 1γ (TIF‐1γ) are frequently associated with increased risk of malignancy, a specific cutaneous phenotype and limited response to therapy in adult DM patients. Anti‐Mi‐2 autoantibodies, in contrast, are typically associated with classic DM rashes, prominent skeletal muscle weakness, better therapeutic response and prognosis, and less frequently with cancer. Nevertheless, the sensitivity of autoantibody testing is only moderate, and alternative reliable methods for DM patient stratification and prediction of cancer risk are needed. To further investigate these clinically distinct DM subgroups, we herein analyzed 30 DM patients (n = 15 Mi‐2+ and n = 15 TIF‐1 γ+) and n = 8 non‐disease controls (NDC). We demonstrate that the NanoString technology can be used as a very sensitive method to clearly differentiate these two clinically distinct DM subgroups. Using the nCounter PanCancer Immune Profiling Panel™, we identified a set of significantly dysregulated genes in anti‐TIF‐1γ+ patient muscle biopsies including VEGFA, DDX58, IFNB1, CCL5, IL12RB2, and CD84. Investigation of type I IFN‐regulated transcripts revealed a striking type I interferon signature in anti‐Mi‐2+ patient biopsies. Our results help to stratify both subgroups and predict, which DM patients require an intensified diagnostic procedure and might have a poorer outcome. Potentially, this could also have implications for the therapeutic approach. [ABSTRACT FROM AUTHOR]

The Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA). To evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM. Adult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed. MSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age [40 (30–49), 13 (7.5–16) years] and disease duration [ 7 (3–17), 6 (2–17) months] comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children. Myositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort., Methods: Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features., Results: Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM ( n  = 23), DM ( n  = 21), ASS ( n  = 23), and IBM ( n  = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA ( n  = 53), myositis-associated antibodies, MAA ( n  = 33), both MSA + MAA ( n  = 24), MSA only ( n  = 29), MAA only ( n  = 9), no MSA, or MAA ( n  = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected., Discussion: The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Marklund, Hanna, Jin and Pullerits.)

Aims: Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear. Methods: In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios. Results: In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively. Conclusion: In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases characterized mainly by inflammation of muscle tissue. Although IIM traditionally encompasses polymyositis, dermatomyositis (DM), and inclusion body myositis, the disease concept has been changing in association with progress in diagnostic techniques. Thus, the new disease entities of amyopathic DM (ADM) or clinically ADM and immune-mediated necrotizing myopathy have been recognized recently. Because of the variety of symptoms or low prevalence or difficulty in correct evaluation of muscle strength and function in IIM patients, no standard treatment strategies have been established yet. Currently, glucocorticoids remain the first line of treatment of IIMs, but in addition to these, several other immunosuppressive agents or intravenous immunoglobulin have been used in a variety of different combinations. However, due to clinical heterogeneity of these conditions as well as the number of therapeutic target organs, IIM therapy remains challenging, and refractory cases are especially difficult to treat. In recent years, new therapeutic approaches using biologics or Janus kinase inhibitors, plasma exchange therapy, and other agents have been evaluated for IIMs. However, validation of the efficacy of these new treatment options remains an issue to be resolved. In this article, the author reviews current treatment strategies and new emerging therapies for IIM patients. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most frequent malignancy in men worldwide and the fifth leading cause of death. Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by musculocutaneous manifestations. However, DM can also present as a paraneoplastic syndrome of an underlying neoplasm. We report a case of a 65-year-old man diagnosed with prostate adenocarcinoma in the setting of severe dysphagia, muscle weakness and a facial erythematous rash. At first, the DM-related symptoms resolved with the initial treatment for the underlying malignancy. Yet, they flared up as the tumor progressed. To sum up, DM is a rare systemic disorder with unknown etiology. There is a well-established association between DM and malignancy. Malignancy-headed therapy can improve DM manifestations and the recurrence of DM symptoms may act as an early warning of malignancy relapse. [ABSTRACT FROM AUTHOR]

Objectives: Idiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP., Methods: This descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients' medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia., Results: A total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan-Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p  = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936-5.392, p  = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072-10.017, p  = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974-38.157, p  = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115-0.899, p  = 0.031)., Conclusion: Approximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Sun, Yu, Du and Ye.)

Calcinosis, or the deposition of insoluble calcium salts in the skin, subcutaneous tissue, fascia, tendons, and muscles, is a feared complication of juvenile dermatomyositis. Calcinosis is estimated to affect up to 40% of patients with juvenile dermatomyositis and contributes to significant disease morbidity. Calcinosis can be challenging to treat, and the most effective treatment remains unknown because of a lack of comparative studies. We aim to review the literature published in the last 5 years to summarize updates on the pathogenesis and treatment of calcinosis in juvenile dermatomyositis and describe future areas for research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pinotti, Cannon, Dvergsten and Wu.)

We aimed to study the prevalence and clinical associations of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in a large cohort of Indian patients with idiopathic inflammatory myositis (IIM). Clinical details and serum samples were collected from patients with IIM (satisfying Bohan and Peter Criteria, 1975) and CTD-associated myositis. Sera were analysed for antibodies against SRP, Mi2, Jo1, PL7, PL12, EJ, OJ, Ro52, Ku, Pm-Scl 75 and PM-Scl 100, using immunoblot assay. The cohort comprised 124 patients with IIM (M:F = 1:3.6). Fifty-five of them had dermatomyositis (DM), 22 had juvenile dermatomyositis (JDM), 25 had polymyositis (PM) and 22 had connective tissue disease-associated myositis (CTD myositis). Mean disease duration was 10.9 months. ANA was positive in 84 (68.9 %), and MSAs in 61 (49.2 %) patients. Among MSAs, autoantibodies to Mi2, synthetase (Jo1, PL7, PL12, EJ) and SRP were present in 26 (20.9 %), 29 (23.4 %) and 6 (4.8 %) patients, respectively. Prevalence of MAAs was as follows: antibodies to Ro52 in 45 (36.3 %), Ku and PM-Scl 75 in 13 (10.5 %) and PM-Scl 100 in 5 (4 %) patients. Anti-Mi2 antibodies were positively associated with DM (21/55, 38.2 %; p < 0.0001) and pharyngeal weakness (13/34, 38.2 %; p = 0.004) and negatively associated with ILD (0/28; p = 0.001). ILD and mechanics' hands were significantly more in patients with anti-synthetase antibodies (16/28, 57 % and 14/22, 63.6 %; p < 0.0001). Four of six patients with anti-SRP antibody showed poor response to multiple drugs. Higher prevalence of anti-Mi2 is probably related to higher proportion of patients with DM. Absence of ILD in patients with anti-Mi2 antibody suggests that it may protect against ILD. In Indian population also, anti-synthetase antibodies are associated with ILD, and anti-SRP antibodies with poor response to treatment. [ABSTRACT FROM AUTHOR]

Background: Myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) are clinically useful biomarkers that point to the diagnosis, clinical manifestations, and prognosis of dermatomyositis (DM)., Materials and Methods: To estimate the prevalence of MSA as well as MAA and analyze possible clinical correlations of these autoantibodies in patients diagnosed with DM, we conducted a cross-sectional study of 30 patients who were diagnosed with DM., Results: MSA were positive in 19 patients (63%) in which Mi 2 was positive in 8 (27%) patients, and this was the most frequently found MSA. A total of 11 (36.7%) patients showed positive MAA. AntiPM/Scl 75 and anti-Ro 52 were positive in 5 (16.7%) patients each and these were the most commonly found MAA. Anti-La was absent in all our patients. There were 8 (27%) patients in whom both MSA and MAA were positive. Either MSA and/or MAA were positive in 22 (73%) patients. On a bivariate analysis, the patients who were positive for anti-PM/Scl 75 showed a significant difference in manifesting cutaneous ulcers ( P value 0.023). It was also found that anti-SAE-positive patients showed a significant difference with malignancy ( P value 0.014). Anti-Ro 52-positive patients were less likely to have symmetrical proximal muscle weakness ( P value 0.006)., Conclusions: All patients who were anti-MDA 5 positive had myositis and none of the anti-MDA 5-positive patients had rapidly progressive interstitial lung disease (RPILD). More than one MSA in the same patient was noted in three patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Dermatology Online Journal.)

Patients with muscle disorders can present a diagnostic challenge to physicians because of the different ways they can present and the large number of different underlying causes. Recognition of the 'myopathic phenotype' coupled with investigations usually including electrodiagnostic and histological investigations have been essential for diagnosing the underlying cause of a myopathy. Despite these standard investigations, some patients can remain undiagnosed. New tests including more specific antibody tests for immune-mediated myopathies and the introduction of next-generation sequencing promise to revolutionise diagnostic approaches for immune and inherited myopathies, but clinical expertise remains essential to choose the most appropriate tests and interpret the results. The aim of this review is to provide an overview of the different presentations to the neuromuscular clinic and the latest investigations that can be helpful in the diagnosis of muscle disorders. [ABSTRACT FROM AUTHOR]

Introduction: Immune-mediated myopathies are a heterogeneous group of chronic autoimmune disorders. Autoantibodies associated with this disease complex are classified into myositis-associated and myositis-specific. Anti-tRNA synthetase antibodies are the most well known of the myositis-specific antibodies. Previous reports have revealed an association of tRNA synthetase autoantibodies with systemic connective tissue disorders. Methods: Our case report involved a 49-year-old man who developed difficulty walking and climbing stairs 5 months prior to his initial visit. No rash or skin changes were observed. Results: Laboratory testing was positive for anti-PL12 autoantibody with a negative evaluation for connective tissue disorder (CTD). The patient was found to have necrotizing myopathy associated with anti-PL12 antibodies in the absence of inflammatory changes on biopsy, significant derangement of muscle enzymes, or findings characteristic of a typical CTD. Conclusion: A high index of suspicion must be maintained for immune-mediated necrotizing myopathy despite the absence of an identifiable CTD and milder symptoms. Muscle Nerve 46: 282-286, 2012 [ABSTRACT FROM AUTHOR]

A small proportion of patients with rheumatoid arthritis (RA) develop idiopathic inflammatory myopathies (IIM); however, the clinical and immunological characteristics of these patients have not been elucidated. In the present study, we evaluate the frequency of autoantibodies and the accompanying clinical features in patients with IIM overlapped to RA (IIM-RA) and in patients with IIM without RA. Twelve patients with IIM-RA were selected from 142 patients with IIM who were admitted to our hospital. Clinical and laboratory data, including autoantibody test results, were collected from patient medical records. Myositis-specific antibodies (MSAs) were analyzed by immunoprecipitation. Clinically, patients with IIM-RA were more likely to be male, to have polymyositis, and to be older at the time of IIM onset than patients with IIM without RA. Patients with IIM-RA had been treated for 2-25 years prior to the onset of IIM with more than two disease-modifying antirheumatic drugs (DMARDs). Patients with IIM-RA had a high frequency (75.0%) of positivity for MSAs, including anti-Jo-1, anti-PL-7, anti-PL-12, or anti-signal recognition particle (SRP) antibodies; anti-Jo-1 antibody was detected in 4 patients (33.3%). In addition, 2 out of 12 patients with IIM-RA were concurrently positive for two different MSAs, anti-Jo-1, and anti-PL-7 antibodies. In 3 other patients with IIM-RA, anti-Jo-1 antibody, or anti-PL-7 antibody was detected in serum samples collected 6-18 months prior to development of myositis. High frequency and coexistence of MSAs were detected in patients with IIM-RA. MSAs detected in patients with RA even without symptoms of myositis may indicate possible future development of myositis. [ABSTRACT FROM AUTHOR]

We encountered a 30-year-old woman who developed dermatomyositis during pregnancy and was positive for anti-Mi-2 antibodies. She was successfully treated with prednisolone and tacrolimus and delivered a healthy child. We reviewed the cases of idiopathic inflammatory myositis (IIM) that developed during pregnancy that were published after the year 2000 to elucidate the profile of myositis-specific antibodies (MSAs) in them and to evaluate their obstetric outcomes. In cases with IIM that developed during pregnancy, anti-Mi-2, anti-TIF1-g, anti-Jo-1, and anti-EJ antibodies was detected in one case each. The obstetric outcomes of the IIM-complicated pregnancies were poor, especially when complicated with active maternal myositis. Further studies focusing on the possible causal relationships between MSAs and cases with IIM that developed during pregnancy are needed. For better obstetric outcomes, appropriate suppression of the maternal disease activity using immunosuppressants and vigilance regarding the patient's requirement of Caesarean section is important.

Myositis-related interstitial lung disease presents with a wide variety of lesions, ranging from chronic to acute. It can be divided into two main forms by the types of onsets, namely, chronic to subacute type showing nonspecific interstitial pneumonia (NSIP) or NSIP with an organizing pneumonia (OP)/fibrosing OP (FOP) pattern and acute type showing acute lung injury (ALI) to diffuse alveolar damage (DAD) pattern. Anti-aminoacyl tRNA Synthetase antibody-positive cases mainly show an NSIP or FOP pattern, whereas anti-melanoma differentiation-associated gene 5 antibody-positive cases show ALI to DAD pattern. Bilateral consolidation with or without ground-glass opacification with lower lobe predominance is common as a major pattern in all types, but the distribution or extent is sometimes different. The early detection of findings that indicate a rapid progressive course is vital. Diffuse cranio-caudal distribution and multiple ground-glass opacifications with random distribution might indicate a poorer prognosis.

Dermatomyositis (DM) is a systemic idiopathic inflammatory disease affecting skeletal muscle and skin, clinically characterized by symmetrical proximal muscle weakness and typical skin lesions. Recently, myositis-specific autoantibodies (MSA) became of utmost importance because they strongly correlate with distinct clinical manifestations and prognosis. Antibodies against transcription intermediary factor 1γ (TIF-1γ) are frequently associated with increased risk of malignancy, a specific cutaneous phenotype and limited response to therapy in adult DM patients. Anti-Mi-2 autoantibodies, in contrast, are typically associated with classic DM rashes, prominent skeletal muscle weakness, better therapeutic response and prognosis, and less frequently with cancer. Nevertheless, the sensitivity of autoantibody testing is only moderate, and alternative reliable methods for DM patient stratification and prediction of cancer risk are needed. To further investigate these clinically distinct DM subgroups, we herein analyzed 30 DM patients (n = 15 Mi-2 + and n = 15 TIF-1 γ + ) and n = 8 non-disease controls (NDC). We demonstrate that the NanoString technology can be used as a very sensitive method to clearly differentiate these two clinically distinct DM subgroups. Using the nCounter PanCancer Immune Profiling Panel™, we identified a set of significantly dysregulated genes in anti-TIF-1γ + patient muscle biopsies including VEGFA, DDX58, IFNB1, CCL5, IL12RB2, and CD84. Investigation of type I IFN-regulated transcripts revealed a striking type I interferon signature in anti-Mi-2 + patient biopsies. Our results help to stratify both subgroups and predict, which DM patients require an intensified diagnostic procedure and might have a poorer outcome. Potentially, this could also have implications for the therapeutic approach., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)