Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.

OBJECTIVES: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. METHODS: Serum samples from patients within the MyoCite cohort, a well-characterised retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patient serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against Immunoprecipitation as the reference standard, measuring sensitivity, specificity, and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific MSA. RESULTS: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83, and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and Immunoprecipitation, and κ values for LIA's for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2, and anti-SAE ranged between 0.21-0.60. CONCLUSION: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5, and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor.

Mental health in paediatric and adult myositis-related diseases: current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group.

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking.Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Digital Health and Self-Management in Idiopathic Inflammatory Myopathies: A Missed Opportunity?

PURPOSE OF REVIEW: This paper explored the potential of digital health in idiopathic inflammatory myopathies (IIMs), with a focus on self-management. Digital self-management technology includes tailored treatment plans, symptom tracking, educational resources, enhanced communication, and support for long-term planning. RECENT FINDINGS: After arguing the importance of digital health in IIMs management, from diagnosis until treatment, our literature review revealed a notable gap in research focusing on the efficacy of digital self-management interventions for individuals with IIMs, with no randomised controlled trials or observational studies addressing this topic. Our review further highlighted the significant unmet need for research in self-management interventions for individuals with IIMs. The absence of studies underscores the necessity for collaborative efforts to address this gap and develop personalised, effective strategies for managing IIMs using digital technology. Individuals with IIMs deserve tailored self-management approaches akin to those available for other rheumatic and musculoskeletal diseases.

COVID-19 severity, breakthrough infections and vaccine safety in young individuals with autoimmune diseases: insights from the COVAD study.

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Breakthrough SARS-CoV-2 infection in fully vaccinated patients with systemic lupus erythematosus: results from the COVID-19 Vaccination in Autoimmune Disease (COVAD) study.

OBJECTIVE: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). METHODS: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models. RESULTS: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89-6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04-5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively. CONCLUSION: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

CAse-BAsed REview sTandards (CABARET): Considerations for Authors, Reviewers, and Editors.

The publication landscape for case reports has undergone a significant shift, with many high-impact journals deprioritizing or ceasing their publication altogether. This trend has led to the emergence of case-based reviews as an alternative to traditional case reports. Several factors drive this shift. Case-based reviews offer a more comprehensive synthesis of the literature compared to single case reports. They employ systematic search methodologies, reducing the risk of excluding relevant data, and providing robust evidence. From a publisher's perspective, case-based reviews have a greater potential for citation. While recommendations exist for writing traditional case reports, such as the CAse REports (CARE) guidelines, there is a lack of published recommendations for composing case-based reviews. This review aims to address this gap by providing guidance on drafting high-quality case-based reviews.

The curious case of subcutaneous dirofilariasis mimicking a fibroma - Report of a rare disease from North India.

ABSTRACT: Human dirofilariasis is a rare arthropod-borne zoonotic infection caused by a filarial nematode of the genus Dirofilaria. It typically manifests in humans as pulmonary, ocular, or subcutaneous lesions. In India, the disease is predominantly seen in the southern states, especially Kerala. Cases documented from India are mostly of ocular infection, and very few cases of subcutaneous dirofilariasis (SD) are reported. We hereby present a case of SD in a 25-year-old male, clinically diagnosed to have fibroma of the left forearm. Histopathology confirmed the diagnosis of SD. We present this case to reiterate that SD, though very rare in North India, should always be considered as a differential for subcutaneous swellings.

Idiopathic pulmonary haemosiderosis.

In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.

Prompt engineering: The next big skill in rheumatology research.

Large language models (LLMs) like GPT-4 and Claude are catalyzing transformation across medical research including rheumatology. This review examines their applications, highlighting the pivotal role of prompt engineering in effectively guiding LLMs. Key aspects explored include literature synthesis, data analysis, manuscript drafting, coding assistance, privacy considerations, and generative artificial intelligence integrations. While LLMs accelerate workflows, reliance without apt prompting jeopardizes accuracy. By methodically constructing prompts and gauging model outputs, researchers can maximize relevance and utility. Locally run open-source models also offer data privacy protections. As LLMs permeate rheumatology research, developing expertise in strategic prompting and assessing model limitations is critical. With proper oversight, LLMs markedly boost scholarly productivity.

"Cell blocking" the parasitic imposter: In a rare case of isolated pulmonary cysticercosis.

Isolated pulmonary cysticercosis is a rare manifestation of human cysticercosis which mainly affects central nervous system, skeletal muscles, eyes and subcutaneous tissues. Pulmonary involvement is usually a part of disseminated disease and mainly presents as bilateral pulmonary nodules. We report a rare case of isolated pulmonary cysticercosis presenting as lung cyst with pleural effusion. The diagnosis was made on pleural fluid cytology and cell block preparation. Herein we wish to recapitulate the importance of cell block as a diagnostic aid for parasitic infections, where morphological features and architectural patterns are as clearly discernable as in histopathology.

Idiopathic inflammatory myopathies: current insights and future frontiers.

Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle injury. Until recently, there was little insight into the pathogenesis of idiopathic inflammatory myopathies, which challenged the recognition of the breadth of heterogeneity of this group of diseases as well as the development of new therapeutics. However, the landscape of idiopathic inflammatory myopathies is evolving. In the past decade, advances in diagnostic tools have facilitated an enhanced understanding of the underlying disease mechanisms in idiopathic inflammatory myopathies, enabling the expansion of therapeutic trials. The fields of transcriptomics, prot§eomics, and machine learning offer the potential to gain greater insights into the underlying pathophysiology of idiopathic inflammatory myopathies. Harnessing insights gained from these sophisticated tools could contribute to the identification of differences at a molecular level among patients, accelerating the development of targeted, tailored therapies. Bolstered by the validation and standardisation of robust outcome measures, many promising therapies are in clinical trial development. Although challenges remain, there is great optimism in the field due to the progress in innovative diagnostics, outcome measures, and therapeutic approaches. In this Review, we discuss the expanding landscape of idiopathic inflammatory myopathies as the frontier of precision medicine becomes imminent.

Content analysis of patient support groups related to myositis on Facebook.

INTRODUCTION: Idiopathic inflammatory myopathies (IIM) are heterogeneous and complex, and routine consultation can be overwhelming for patients, or sometimes so rushed that patients feel unable to discuss their needs and wishes adequately. As a result, online patient support groups (PSGs) on social media platforms like Facebook may help provide them with information they are seeking, and the support of the patient community who are living with this condition. Our goal is to explore the current landscape of PSGs in IIM to discuss the future of such groups and their role in supporting patient-driven self-management of complex connective tissue diseases. METHODS: We investigated factors that influence engagement in publicly accessible support groups on Facebook for patients with myositis. We analysed posts from myositis-related Facebook groups and pages between July 10, 2022, and October 2022. Data were extracted from each post, including presentation format (text, picture, video or mixed media) and content type (news, personal feelings or information). To gauge the post's impact, we measured engagement metrics, such as likes, comments, shares and reactions. RESULTS: Nearly three-quarters of the groups were private. Among the open ones, most posts seem to comprise pictures with text. Notably, engagement levels were higher for multimedia posts, with the exception of comments in groups, where engagement was comparatively lower. In terms of content, the majority of posts fell under the 'personal' category, followed by 'information' and 'news' posts, with information posts in groups receiving the most interactions. Moreover, groups exhibited higher total engagement compared to pages when considering all posts cumulatively. CONCLUSIONS: Our observations indicate that patients with myositis seek information on the condition online, and the multimedia nature of content presentation significantly influences engagement. These digital forums serve as valuable platforms for fostering connections among diverse individuals, providing a perceived safe space for sharing their personal experiences and varied perspectives, and potentially mitigating social isolation. Key Points • Patient support groups on myositis are a key source of support and information for patients. • Public posts with multimedia content garner the most engagement. • The majority of posts are personal in nature, with a smaller proportion of content providing news or information.