Myositis-specific Antibodies Research Articles

Case Report: IVIG causing bilateral papilledema and increased intracranial hypertension in patients with anti-TIF-1γ antibody-positive JDM

Juvenile dermatomyositis is a systemic autoimmune disease characterized by progressive proximal muscle weakness, pathognomonic rashes, and often the presence of myositis-specific antibodies. Consensus treatment plans for pediatric patients with juvenile dermatomyositis recommend steroids and methotrexate as initial therapy. Patients with anti-transcription intermediary factor 1 gamma (anti-TIF-1γ) antibodies tend to have more refractory disease requiring more aggressive treatment with intravenous immunoglobulin, which is typically well tolerated. We describe two pediatric patients diagnosed with anti-TIF-1γ antibody-positive juvenile dermatomyositis who developed persistent increased intracranial pressure following intravenous immunoglobulin treatment. These cases suggest a potential association between treatment with intravenous immunoglobulin and increased intracranial pressure, a side effect that is not readily known. The shared anti-TIF-1γ positivity in both patients may suggest a possible concern for intracranial hypertension among juvenile dermatomyositis patients with this myositis-specific antibody.

The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort

Background Inflammatory idiopathic myopathies (IIM) are a heterogeneous group of complex connective tissue diseases (CTD), primarily characterized by inflammatory involvement of skeletal muscles. Several other organs may also be affected, including lungs, heart, skin, gastrointestinal tract, and joints. Objective Describe the clinical and immunological characteristics of IIM among Tunisian patients. Method A retrospective study conducted in the internal medicine department at the Rabta Hospital over 22 years, including adult patients with IIM according to the ACR/EULAR classification criteria, and anti-synthetase syndrome (ASS) according to Connors’ criteria. Inclusion body myositis was excluded. Demographic, clinical, and immunological characteristics were analyzed. Results Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). The ACR/EULAR criteria enabled the inclusion of 88% of the patients. Dermatomyositis (DM) was the most frequent entity (47%), followed by Polymyositis (PM) (36%) and Amyotrophic dermatomyositis (ADM) (4%). Connors criteria allowed the inclusion and classification with ASS of 33 patients, including those excluded by the ACR/EULAR criteria (12%). Muscular involvement was present in 88% of patients, affecting locomotor (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) muscles. Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. ILD was reported across all subgroup: ASS (85%), PM (57%), DM (17%), and ADM (100%). NSIP was the most common radiologic pattern (59%). Skin involvement (85%), consistently present in DM and ADM, affected 91% of ASS patients. Joint involvement (48%) was predominantly polyarticular (68%). Myositis-specific antibodies (MSAs) were detected in 52% of patients, with a predominance of anti-synthetase antibodies (ASAs). Another CTD was noted in 24% of patients and cancer in 17% of patients. Conclusion Our study underscored the clinical diversity among IIM patients and the systemic nature of these diseases, where muscular involvement is not always uniform.

Anti-MDA5 positivity: describing the frequency and spectrum of clinically evident MDA5 disease.

To evaluate experience in a tertiary rheumatology service with melanoma differentiation-association-protein-5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti-MDA5 positivity was detected in 2% of myositis-specific antibody tests. Of these, 29% did not have features consistent with anti-MDA5 disease. However, when present, MDA5 disease is severe with a high mortality.

Prognostic value of myositis-specific antibodies in patients with idiopathic interstitial pneumonia

BackgroundPatients with idiopathic interstitial pneumonia (IIP) often exhibit positivity for myositis-specific antibodies (MSA). However, the significance of this finding remains unclear. In this study, we investigated the association of MSA with the prognosis and risk of acute exacerbation in patients with IIP.MethodsWe retrospectively reviewed the medical records of patients with IIP and examined the effect of each MSA subtype on survival and acute exacerbation.ResultsOf 240 patients with IIP, 48 (20%) exhibited positivity for MSA. The MSA subtypes included: PL-7 (antithreonyl; n = 16, 6.7%); signal recognition particle (n = 13, 5.4%); PL-12 (antialanyl; n = 9, 3.8%); Mi-2 (n = 8, 3.3%); OJ (anti-isoleucyl; n = 7, 2.9%). During the 382 days (382 ± 281 days) of observation, 32 (13%) patients expired, and 27 (11%) experienced an acute exacerbation. Cox proportional hazards regression analysis demonstrated that age at the initial visit (hazard ratio [HR]: 1.072; 95% confidence interval [CI]: 1.017–1.131; P = 0.01), PL-7 (HR: 4.785; 95% CI: 1.528–14.925; P = 0.007), and PL-12 (HR: 3.922; 95% CI: 1.198–12.82; P = 0.024) were independent predictors of survival time. PL-7 (HR: 3.268; 95% CI: 1.064–10; P = 0.039) and PL-12 (HR: 5.747; 95% CI: 1.894–7.544; P = 0.002) were independent predictors of time from first visit to acute exacerbation.ConclusionDetecting MSA in patients with interstitial lung disease may be useful in predicting prognosis and providing a rationale for intensive treatment.

Over Activation of IL-6/STAT3 Signaling Pathway in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM. Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells. IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ(TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells. IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.

Comparison of Lineblot and Immunoprecipitation Methods in the Detection of Myositis-Specific and Myositis-Associated Antibodies in Patients with Idiopathic Inflammatory Myopathies: Consistency with Clinical Diagnoses.

Background: the reference method for detection of myositis-specific and myositis-associated antibodies (MSAs and MAAs) is considered immunoprecipitation (IP), but it is routinely replaced by semi-automated methods, like lineblot (LB). Few data are available on the consistency with clinical diagnoses; thus, we aim at analysing these aspects. Methods: sixty-nine patients with idiopathic inflammatory myopathies (IIM) were studied via LB (Myositis Antigens Profile 3 EUROLINE, Euroimmun) and IP (RNA and protein antigens). The degree of concordance between methods was calculated using Cohen's coefficient. Results: a substantial concordance was found for anti-Ku and anti-PM/Scl and a moderate concordance was found for anti-Jo1 and anti-Mi-2, while a fair concordance was found for anti-EJ, anti-SRP, and anti-Ro52 antibodies. The concordance could not be calculated for anti-OJ, anti-PL-7, anti-PL-12, anti-NXP2, anti-TIF1ɣ, and anti-MDA5, because they were only detected with one method. Multiple MSAs were found only with LB in 2/69 sera. Anti-MDA5, TIF1ɣ, NXP2 (detected via IP), and anti-Jo1 in anti-synthetase syndrome (both LB and IP) had the best concordance with clinical diagnosis. Conclusions: LB and IP show substantial concordance for PM/Scl and Ku, and moderate concordance for Jo1 and Mi-2, with a good concordance with clinical diagnoses. IP shows a high performance for DM-associated MSAs. LB seems to be more sensitive in detecting anti-Ro52 antibodies, but it identified multiple MSAs, unlike IP.

Mini review of diagnostic and therapeutic approaches in myositis-associated interstitial lung disease

Myositis-associated interstitial lung disease (ILD) presents a significant challenge in terms of diagnosis and management due to its heterogeneity and potential for rapid progression. This review outlines the current strategies for diagnosing and managing myositis-associated ILD, focusing on mild to moderate and severe or rapidly progressive cases. Initial diagnosis involves comprehensive clinical evaluation, high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and serological testing for myositis-specific antibodies and myositis-associated antibodies. Management of mild to moderate ILD includes using corticosteroids and steroid-sparing agents, supported by oxygen therapy, pulmonary rehabilitation, and preventive vaccinations. Regular monitoring through PFTs, HRCT, and clinical assessments is essential to ensure effective management and detect disease progression. In cases of severe or rapidly progressive ILD, aggressive treatment with high-dose corticosteroids, additional immunosuppressive agents such as cyclophosphamide, rituximab, and calcineurin inhibitors, and the use of anti-fibrotic agents like Nintedanib and Pirfenidone are crucial. Supportive care measures, including oxygen therapy and mechanical ventilation, may be necessary for patients with severe respiratory failure. Implementing structured algorithms for diagnosis and management helps streamline the process and improve patient outcomes. Continuous research and advancements in immunology and pharmacology are essential for developing more effective treatments for this challenging condition.

14-month-old female with anti-MDA5 juvenile dermatomyositis complicated by liver disease: a case report

BackgroundJuvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy.Case presentationA previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her bilateral elbows, forearms, arms, and knees, arthritis, Gottron’s sign, and hepatomegaly. The patient was admitted, and symptoms progressed to include hypoxemia. Subsequent workup was notable for ground glass opacities of bilateral lung fields on chest CT, myositis visualized on MRI and confirmed with muscle biopsy, and liver biopsy showing nonspecific signs of liver injury. After a thorough infectious disease workup to rule out concomitant infection, the patient was started on high-dose steroids and induction with cyclophosphamide. She responded well with disease remission maintained with tofacitinib in the outpatient setting.Discussion and conclusionsOur patient is notable due to her young age at presentation, histopathologically confirmed liver injury, and response to treatment. The case adds to the growing body of literature supporting tofacitinib for anti-MDA5 JDM in the pediatric population. Future research can better standardize effective treatment protocols and define the mechanism of liver involvement. For patients with nonspecific liver injury, muscular, and cutaneous disease, anti-MDA5 JDM should be considered in the differential diagnosis with treatment options including tofacitinib for confirmed cases.

Pharmacological Strategies in Dermatomyositis: Current Treatments and Future Directions.

Dermatomyositis (DM) is a complex and rare autoimmune disease characterized by muscle weakness and distinctive skin rashes. Its pathogenesis involves a combination of genetic susceptibility, environmental triggers, and immunological factors, with interferon pathways and specific gene upregulations playing crucial roles. Diagnosis is based on clinical presentation, laboratory findings, and imaging, with particular emphasis on myositis-specific antibodies and characteristic muscle and skin changes. The clinical heterogeneity of DM, including variants such as clinically amyopathic DM and DM-associated interstitial lung disease, necessitates a personalized diagnostic and therapeutic approach. Current pharmacological treatments for DM include glucocorticoids, which remain the first-line therapy despite their long-term adverse effects. Immunosuppressants, such as azathioprine, methotrexate, and mycophenolate mofetil, are commonly used in combination with glucocorticoids to enhance efficacy and reduce steroid dependence. Biologics, such as rituximab and intravenous immunoglobulin, have shown effectiveness in refractory cases. Emerging therapies, particularly Janus kinase inhibitors, offer promise for treatment-resistant DM, although they present significant safety concerns, including increased risks of infections and cardiovascular events. Despite significant advancements, managing DM remains challenging due to its rarity and variability. Future research should prioritize the development of precision medicine approaches tailored to individual genetic and pathological features. Additionally, integrated treatment strategies combining pharmacological and non-pharmacological interventions are crucial to improving patient outcomes and quality of life. Understanding the etiology and pathogenesis of DM more deeply will be vital for developing more effective and targeted treatments, ultimately leading to better disease management and prognosis.

Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

Idiopathic Inflammatory Myopathies-associated Interstitial Lung Disease in Adults.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases characterized by muscle involvement and various extramuscular manifestations. Interstitial lung disease (ILD) is one of the most common extramuscular manifestations of IIM and is associated with significant mortality and morbidity. The clinical phenotypes, treatment responses, and prognosis of IIM-ILD are significantly related to myositis-specific antibody (MSA) profiles, with some racial differences. The features associated with MSA in IIM-ILD could also be relevant to cases of ILD where MSA is present but does not meet the criteria for IIM. The anti-melanoma differentiation-associated gene 5 antibody is highly associated with rapidly progressive ILD (RP-ILD), especially in Asian populations, and with characteristic cutaneous manifestations, such as skin ulcers. Radiologically, ground-glass opacities, consolidations, and nonsegmental linear opacities were more predominant than reticular opacities and honeycombing. While the mortality rate is still around 30%, the prognosis can be improved with early intensive therapy with corticosteroids and multiple immunosuppressants. In contrast, anti-aminoacyl-tRNA synthetase (ARS) antibodies are associated with chronic ILD, although RP-ILD is also common. Patients with anti-ARS antibodies often show lung-predominant presentations, with subtle muscle and skin involvement. Radiologically, reticular opacities, with or without consolidation, are predominant and may progress to honeycombing over time. Combination therapy with corticosteroids and a single immunosuppressant is recommended to prevent relapses, which often lead to a decline in lung function and fatal long-term outcomes. Significant advances in immunology and genetics holds promise for fostering more personalized approaches to managing IIM-ILD.

The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort

Background Idiopathic inflammatory myopathies (IIM) encompass a heterogenous group of auto-immune diseases. The identification of myositis specific antibodies (MSA) and their associations with distinct phenotypes has improved the categorization of these conditions. Objective The aim of this study was to describe and report the clinical and immunological characteristics of IIM among Tunisian patients. Method A retrospective study conducted in the internal medicine department at the Rabta University Hospital Center over 22 years, including adult patients with IIM according to the American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria and Connors’ criteria for anti-synthetase syndrome (ASS). Inclusion body myositis and myositis associated with other conditions were excluded. Demographic, clinical, and immunological characteristics were analyzed and compared. Results Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). Muscular involvement was present in 88% of patients, affecting locomotor muscles (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) systems. Muscle weakness was primarily noted in the pelvic girdle (81%), scapular region (74%), axial muscles (20%), and distal muscles (5%). Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. Diffuse interstitial pneumonia (DIP) was present in 45% of patients, cutaneous involvement in 85%, and articular involvement in 48%. MSAs were detected in 52% of patients. Analysis revealed significantly higher frequencies of amyopathic forms, DIP, palmar hyperkeratosis, and articular involvement in the ASS group. The DM group exhibited higher frequencies of gastrointestinal signs, Gottron’s papules, heliotrope rash, photosensitive rashes, ulcerations, and skin necrosis. The NAM group had higher frequencies of gastrointestinal signs, myolysis, and lower frequencies of DIP and cutaneous involvement. Conclusion Our findings corroborate previously established clinico-immunological associations reported in the literature underscoring the need for a combined clinico-serological approach in classifying IIM.

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.

Clinical characteristics of idiopathic inflammatory myopathies patients with anti-PM/Scl antibodies

ObjectivesTo analyze the clinical features of idiopathic inflammatory myopathies (IIMs) patients with anti-PM/Scl antibodies. MethodsIn this retrospective cohort study, we compared the clinical manifestations between patients who were solely positive for anti-PM/Scl antibodies (isolated anti-PM/Scl group) and those with a coexistence of anti-PM/Scl antibodies and myositis-specific antibodies (MSAs) (double-positive group). ResultsSixty-five IIMs patients positive for anti-PM/Scl antibodies were included, among whom 51 (78.5 %) were females, with a mean age of 49.1 years. Thirty-four (52.3 %) patients coexisted with MSAs. Compared to the double-positive group, the isolated anti-PM/Scl group demonstrated a higher proportion of women (90.3 % vs 67.6 %, p = 0.026) and a higher incidence of sclerodactyly (16.1 % vs 0, p = 0.021). Although there were no differences in the incidence of muscular weakness, dysphagia, or creatine kinase levels, thigh magnetic resonance imaging (MRI) revealed less muscle edema, atrophy, and fatty replacement in the isolated anti-PM/Scl group (p < 0.05). Interstitial lung disease (ILD) occurred in 80 % of patients, more frequently in the double-positive group (90.6 % vs 67.9 %, p = 0.028). According to HRCT, non-specific interstitial pneumonia (NSIP) was the most common pattern among anti-PM/Scl antibodies positive IIMs patients. The double-positive group exhibited higher ferritin levels, and a lower peripheral lymphocyte count (p < 0.05). The mortality rate in the double-positive group was higher than that in the isolated anti-PM/Scl group (20.6 % vs 0, p = 0.034). ConclusionAmong IIMs patients who tested positive for anti-PM/Scl antibodies, ILD emerged as the predominant clinical feature, particularly when combined with MSA. Notably, patients with isolated anti-PM/Scl antibodies exhibited a favorable prognosis following immunotherapy.

Characterization of scalp involvement in dermatomyositis based on myositis-specific antibody subsets

Characterization of scalp involvement in dermatomyositis based on myositis-specific antibody subsets

Clinical characteristics and prognostic factor in juvenile dermatomyositis: data of the Spanish registry

BackgroundJuvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients.MethodsWe retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity.ResultsOne hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5–10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22–47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5–34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6–22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications.ConclusionsWe describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication.

Muscle biopsy practices in the evaluation of idiopathic inflammatory myopathies: An international survey of expert clinicians

BackgroundMuscle biopsy is an important test in the evaluation of individuals with suspected myopathy, including those with suspected idiopathic inflammatory myopathy (IIM). Various approaches, including open surgical biopsy, needle biopsy and conchotome forceps, have been reported. However the real-world utilisation of these approaches remains unclear. There are no established guidelines for the use of muscle biopsy, or selection of biopsy technique, in investigating IIM and international practices are not well-documented. This study describes current approaches to muscle biopsy amongst clinicians with expertise in IIM. MethodsA survey regarding muscle biopsy practices was disseminated among members of the International Myositis Assessment and Clinical Studies (IMACS) group. Data were analysed using descriptive statistics. ResultsOne-hundred and sixteen clinicians completed the survey, primarily rheumatologists. Open surgical biopsy was the most commonly employed technique (74.5 %), followed by needle (11.3 %) and conchotome (9.4 %) approaches. Clinical examination was the most common method of muscle selection, with 85.2 % of respondents reporting they ‘always or almost always’ relied on it. MRI and electromyography were also frequently utilised for muscle selection (51.9 %, 45.4 % respectively). There was variability in the perceived utility of muscle biopsy in certain clinical contexts, such as presence of myositis specific antibodies or cutaneous manifestations of dermatomyositis. While respondents generally reported low complication rates following muscle biopsy, non-diagnostic histopathology was commonly reported, regardless of procedural approach. ConclusionClinicians managing IIM report muscle biopsy to be well tolerated however, non-diagnostic results are common. Substantial heterogeneity regarding perceived indications for biopsy, procedural approaches, and muscle selection strategies were observed within this expert group. Future research is needed to establish best practice and determine the role of muscle biopsy in the context of continued advancements in serological profiling of IIM.

A Review of Myositis-Associated Interstitial Lung Disease.

There is a well-established relationship between different subsets of idiopathic inflammatory myopathies (IIMs, myositis) and interstitial lung disease (ILD), with lung complications sometimes presenting prior to myopathic manifestations. The subtypes of myositis include those that are strongly associated with ILD, such as polymyositis (PM) and dermatomyositis (DM). Research has shown that in certain patients, these can then be further divided into subtypes using myositis-specific antibodies (MSAs), which are specific for myositis, and myositis-associated antibodies (MAAs), which can be found in myositis in overlap syndromes with other connective tissue diseases (CTDs). Notably, certain MSAs and MAAs are associated with ILD in patients with myositis. The clinical presentations of ILD in patients with myositis can vary widely and can be insidious in onset and difficult to diagnose. As ILD can progress rapidly in some cases, it is essential that clinicians are able to identify and diagnose ILD in patients with myositis. For this reason, the aim of this review is to highlight the clinical features, diagnostic criteria, important histopathologic, laboratory, and radiographic features, and treatment modalities for those patients with myositis-associated ILD.

High Prevalence of Myositis-Specific and Associated Antibodies in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time.

Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report

BackgroundNecrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.Case presentationWe describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3–4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.ConclusionsIdentifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.