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Journal of Clinical Rheumatology :... Mar 2022Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) are sometimes associated with autoantibodies, but we do not know how frequently or whether...
BACKGROUND
Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) are sometimes associated with autoantibodies, but we do not know how frequently or whether these autoantibodies are present before ICI initiation. Our aim was to determine the positivity rate of autoantibodies in patients with organ-specific ICI-associated irAEs and determine their value as pretreatment biomarkers.
METHODS
We searched for all English, peer-reviewed publications from MEDLINE, Embase, and Cochrane Library through February 20, 2020, and included any publication describing patients with irAEs and reporting results of any autoantibody investigation. Three reviewers independently extracted data, and 1 reviewer verified all data for accuracy and quality of reporting.
RESULTS
We identified 515 publications. Most reports described endocrine, rheumatic, gastrointestinal/hepatic, and myositis/myasthenia/myocarditis irAEs. Autoantibodies were present in close to 50% of patients with ICI-associated endocrinopathies. Anti-BP180 was found in more than 50% of patients with skin irAEs. Antibodies were also common in patients with the triad of myositis/myasthenia/myocarditis including striational antibodies (49%), acetylcholine receptor antibodies (40%), and myositis-associated antibodies (27%). Only 11% of patients with arthritis had either rheumatoid factor or cyclic citrullinated peptide antibodies, and only 30% of patients with sicca had Sjögren antibodies. Autoantibodies were also relatively uncommon in patients with hepatitis (antinuclear antibody, 18%) and colitis (perinuclear antineutrophil cytoplasmic antibody, 19%). Some cohort studies analyzing pre-ICI seropositivity suggest there may be a role for autoantibodies as biomarkers of irAEs.
CONCLUSIONS
Reported autoantibody positivity is high in irAEs involving the endocrine organs, skin, and muscle, but lower in irAEs affecting other organ systems. Autoantibody investigations in pre-ICI treatment patients have yielded mixed results regarding their utility as a biomarker of irAEs.
Topics: Autoantibodies; Humans; Immune Checkpoint Inhibitors; Myositis; Neoplasms; Rheumatoid Factor
PubMed: 34371516
DOI: 10.1097/RHU.0000000000001777 -
Seminars in Arthritis and Rheumatism Feb 2024The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear. Serum ferritin (SF) is a potential candidate and this systematic review and meta-analysis aimed to reveal the clinical significance of SF in IIM-ILD.
METHODS
Eligible English studies were selected from PubMed, Embase, Web of science and Scopus up to 9 June 2023. The SF levels in patients with IIM-ILD were extracted and pooled. Subgroup analysis was performed based on disease types, sensitivity analysis was conducted by excluding one class of literature at a time, and publication bias was assessed by funnel plot and Egger's test.
RESULTS
Pooled analysis of 1,933 patients with IIM from 19 studies showed that SF levels were significantly higher in IIM-ILD group (WMD=263.53ng/mL, 95% CI: 146.44-380.62, p<0.001) than IIM without ILD, subgroup analysis showed that SF levels in DM-ILD (WMD = 397.67ng/mL, 95% CI:142.84-652.50, p = 0.002) and PM/DM-ILD (WMD = 117.68 ng/mL, 95% CI: 86.32-149.04, p < 0.001) were significantly higher compared to those without ILD. SF levels were significantly higher in rapidly progressive interstitial lung disease group (RP-ILD)(WMD = 484.99 ng/mL, 95% CI: 211.12-758.87, p= 0.001) than chronic ILD(C-ILD) group, subgroup analysis showed that SF levels in DM-RP-ILD (WMD= 509.75 ng/mL, 95% CI: 215.34-804.16, p=0.001) were significantly higher than those in DM-C-ILD group. SF levels were significantly higher in death group (WMD= 722.16 ng/mL, 95% CI: 572.32-872.00, p< 0.001) compared to the survival group, subgroup analysis showed that death patients with DM-ILD(WMD= 735.62 ng/mL, 95% CI:574.92-896.32, p<0.001) and PM-ILD (WMD= 632.56 ng/mL, 95% CI:217.92-1047.19, p=0.003) had significantly higher SF levels than survival group respectively.
CONCLUSION
Increased SF levels can serve as a biomarker for predicting the occurrence, progression and death of patients with IIM-ILD, which can provide early warning sign for intervention and prognosis evaluation for IIM-ILD patients.
Topics: Humans; Myositis; Lung Diseases, Interstitial; Biomarkers; Prognosis; Ferritins; Retrospective Studies
PubMed: 38086199
DOI: 10.1016/j.semarthrit.2023.152350 -
Frontiers in Immunology 2022The SARS-CoV-2 infection has been advocated as an environmental trigger for autoimmune diseases, and a paradigmatic example comes from similarities between COVID-19 and...
INTRODUCTION
The SARS-CoV-2 infection has been advocated as an environmental trigger for autoimmune diseases, and a paradigmatic example comes from similarities between COVID-19 and the myositis-spectrum disease associated with antibodies against the melanoma differentiation antigen 5 (MDA5) in terms of clinical features, lung involvement, and immune mechanisms, particularly type I interferons (IFN).
CASE REPORT
We report a case of anti-MDA5 syndrome with skin manifestations, constitutional symptoms, and cardiomyopathy following a proven SARS-CoV-2 infection.
SYSTEMATIC LITERATURE REVIEW
We systematically searched for publications on inflammatory myositis associated with COVID-19. We describe the main clinical, immunological, and demographic features, focusing our attention on the anti-MDA5 syndrome.
DISCUSSION
MDA5 is a pattern recognition receptor essential in the immune response against viruses and this may contribute to explain the production of anti-MDA5 antibodies in some SARS-CoV-2 infected patients. The activation of MDA5 induces the synthesis of type I IFN with an antiviral role, inversely correlated with COVID-19 severity. Conversely, elevated type I IFN levels correlate with disease activity in anti-MDA5 syndrome. While recognizing this ia broad area of uncertainty, we speculate that the strong type I IFN response observed in patients with anti-MDA5 syndrome, might harbor protective effects against viral infections, including COVID-19.
Topics: Antigens, Differentiation; Autoimmune Diseases; Autoimmunity; Biomarkers; COVID-19; Humans; Interferon Type I; Interferon-Induced Helicase, IFIH1; Melanoma; Myositis; SARS-CoV-2
PubMed: 35833112
DOI: 10.3389/fimmu.2022.937667 -
Clinical and Experimental Rheumatology Feb 2022Dermatomyositis (DM) and juvenile dermatomyositis (JDM) are idiopathic inflammatory myopathies, which can be resistant and unresponsive to initial treatments, leading to...
OBJECTIVES
Dermatomyositis (DM) and juvenile dermatomyositis (JDM) are idiopathic inflammatory myopathies, which can be resistant and unresponsive to initial treatments, leading to severe complications and impaired quality of life. There are few randomised trials in dermatomyositis and the outcomes reported may not be consistent, which can limit decision-making. The aim of this study is to assess the scope and consistency of outcomes reported in randomised trials in dermatomyositis.
METHODS
MEDLINE, Embase, PsycINFO and clinicaltrials.gov were searched from 1993-2020 for randomised trials in children and adults with dermatomyositis. The frequency and characteristics of the outcomes reported were analysed and classified.
RESULTS
20 trials were included. Across these trials, a total of 743 outcome measures were reported, which were grouped into 34 outcome domains; of which 17 were clinical, 13 were surrogate/biochemical, and 4 were patient-reported outcomes. The top five most frequently reported outcome domains were muscle inflammation (15 trials, 46 outcome measures), physical function (14 trials, 16 outcome measures), muscle strength (13 trials, 30 outcome measures), global health (12 trials, 33 outcome measures) and immunologic marker (11 trials, 91 outcomes).
CONCLUSIONS
The majority of outcomes reported in trials in people with dermatomyositis and JDM are clinical and surrogate outcomes rather than patient-reported outcomes. The outcomes reported are very inconsistent across trials, with wide heterogeneity in the measures used. Standardised reporting of critically important outcomes is needed to strengthen the value of trials for decision-making.
Topics: Adult; Child; Dermatomyositis; Humans; Outcome Assessment, Health Care; Patient Reported Outcome Measures; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35225217
DOI: 10.55563/clinexprheumatol/3izscd -
Reumatismo May 2023The COVID-19 pandemic represents a global health problem, which has been mitigated by the opportune introduction of vaccination programs. Although we already know the...
The COVID-19 pandemic represents a global health problem, which has been mitigated by the opportune introduction of vaccination programs. Although we already know the benefit that vaccines provide, these are not exempt from adverse events which can be mild to deadly, such as idiopathic inflammatory myopathies, in which a temporal association has not been defined. It is for this reason that we carried out a systematic review of all reported cases of vaccination against COVID-19 and myositis. To identify previously reported cases of idiopathic inflammatory myopathies associated with vaccination against SARS-CoV-2 we registered this protocol on the website of PROSPERO with identification number CRD42022355551. Of the 63 publications identified in MEDLINE and 117 in Scopus, 21 studies were included, reporting 31 cases of patients with vaccination-associated myositis. Most of these cases were women (61.3%); mean age was 52.3 years (range 19-76 years) and mean time of symptom onset post-vaccination was 6.8 days. More than half of the cases were associated with Comirnaty, 11 cases (35.5%) were classified as dermatomyositis, and 9 (29%) as amyopathic dermatomyositis. In 6 (19.3%) patients another probable trigger was identified. Case reports of inflammatory myopathies associated with vaccination have heterogeneous presentations without any specific characteristics: as a consequence, it is not possible to ensure a temporal association between vaccination and the development of inflammatory myopathies. Large epidemiological studies are required to determine the existence of a causal association.
Topics: Humans; Female; Infant, Newborn; Infant; Male; SARS-CoV-2; Pandemics; COVID-19; Myositis; Vaccination
PubMed: 37154256
DOI: 10.4081/reumatismo.2023.1548 -
Frontiers in Immunology 2021The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes,...
The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes, muscle biopsy, electromyography and changes on magnetic resonance imaging. However, the hallmark of these IIM, is the development of myositis specific antibodies (MSA) or myositis associated antibodies (MAA). The theories about their presence in the serum of IIM is not known. Some studies have suggested that some of these MSA, such as anti-Mi-2 increases according to the intensity of UV radiation. There is scarce information about the environmental factors that might contribute in order to be considered as triggering factors as UV radiation might be. In this review, we analyzed the reported prevalence of MSAs and MAAs regarding to their geographical location and the possible relation with UV radiation. We collected the prevalence data of fifteen MSA and thirteen MAA from 22 countries around the world and we were able to observe a difference in prevalence between countries and continents. We found differences in anti-PL7, anti-Ro52, anti-La and anti-Ku prevalence according to UV radiation level. Otherwise, we observed that anti-Mi-2 prevalence increases near to the Equator meanwhile anti-MJ/NXP2 and anti-ARS prevalence had an opposite behavior increasing their prevalence in the geographical locations farther to the Equator. Our results highlighted the importance to include the UV radiation and other environmental factors in IIM studies, in order to clarify its association with MSA and MAA prevalence as well as its possible role in the immunopathogenesis of these diseases.
Topics: Autoantibodies; Autoimmune Diseases; Geography; Humans; Myositis; Prevalence
PubMed: 33968081
DOI: 10.3389/fimmu.2021.672008 -
Hellenic Journal of Nuclear Medicine 2021The purpose of current investigation was to evaluate the diagnostic accuracy of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of current investigation was to evaluate the diagnostic accuracy of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for the determination of disease activity of idiopathic inflammatory myopathies (IM) using diagnostic accuracy test.
SUBJECTS AND METHODS
The PubMed and EMBASE database, from the earliest available date of indexing through August 31, 2020, were searched for results investigating the diagnostic accuracy of F-FDG PET/CT for the determination of disease activity of IM. We calculated the pooled sensitivities and specificities of included studies, calculated positive and negative likelihood ratios (LR+ and LR-), and obtained summary receiver operating characteristic (SROC) curves.
RESULTS
Across 4 studies with 5 results (90 patients), the pooled sensitivity was 0.94 (95% CI; 0.87-0.97) without heterogeneity (I=0.0, P=0.8) and a pooled specificity was 0.90 (95% CI; 0.72-0.97) with heterogeneity (I=65.1, P=0.02). Likelihood ratio (LR) syntheses showed an overall positive likelihood ratio (LR+) of 9.2 (95% CI; 3.1-28.0) and negative likelihood ratio (LR-) of 0.07 (95% CI; 0.03-0.16). The pooled DOR was 131 (95% CI; 26-664). The hierarchical SROC curve shows the areas under the curve of 0.96 (95% CI; 0.94-0.98).
CONCLUSION
Fluorine-18-FDG PET/CT has a good performance for the detection of active disease status in patients with IM. Although there are no guidelines for adopting imaging techniques, more objective and updated criteria for the assessment of disease activity incorporated with F-FDG PET/CT should be introduced and validated. Further studies are necessary to determine if 18F-FDG PET/CT-based treatment of IM can improve outcomes.
Topics: Fluorodeoxyglucose F18; Humans; Myositis; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 34352048
DOI: 10.1967/s002449912353 -
Journal of Autoimmunity Feb 2021The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the...
The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the initial target of SARS-CoV-2 is the respiratory tract, it is becoming increasingly clear that there is a complex interaction between the virus and the immune system ranging from mild to controlling responses to exuberant and dysfunctional multi-tissue directed autoimmune responses. The immune system plays a dual role in COVID-19, being implicated in both the anti-viral response and in the acute progression of the disease, with a dysregulated response represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinflammation. It has been speculated that these immunological changes may induce the loss of tolerance and/or trigger chronic inflammation. In particular, molecular mimicry, bystander activation and epitope spreading are well-established proposed mechanisms to explain this correlation with the likely contribution of HLA alleles. We performed a systematic literature review to evaluate the COVID-19-related autoimmune/rheumatic disorders reported between January and September 2020. In particular, we investigated the cases of incident hematological autoimmune manifestations, connective tissue diseases, antiphospholipid syndrome/antibodies, vasculitis, Kawasaki-like syndromes, acute arthritis, autoimmune-like skin lesions, and neurologic autoimmune conditions such as Guillain-Barré syndrome. We screened 6263 articles and report herein the findings of 382 select reports which allow us to conclude that there are 2 faces of the immune response against SARS-CoV-2, that include a benign virus controlling immune response and a many faceted range of dysregulated multi-tissue and organ directed autoimmune responses that provides a major challenge in the management of this viral disease. The number of cases for each disease varied significantly while there were no reported cases of adult onset Still disease, systemic sclerosis, or inflammatory myositis.
Topics: Animals; Autoimmune Diseases; COVID-19; Chronic Disease; Humans; Immunity; Incidence; Inflammation; Janus Kinases; SARS-CoV-2
PubMed: 33401171
DOI: 10.1016/j.jaut.2020.102592 -
Frontiers in Endocrinology 2020Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive...
Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive radiographic imaging techniques and genetic analyses, bone biopsies are still valuable in the diagnosis of bone diseases. Advanced techniques for the assessment of bone quality in bone biopsies, which have emerged during the last decades, allows in-depth tissue analyses beyond structural changes visible in bone histology. In this review, we give an overview of the application and advantages of the advanced techniques for the analysis of bone biopsies in the clinical setting of various rare metabolic bone diseases. A systematic literature search on rare metabolic bone diseases and analyzing techniques of bone biopsies was performed in PubMed up to 2019 week 34. Advanced techniques for the analysis of bone biopsies were described for rare metabolic bone disorders including Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, Fibrodysplasia ossificans progressiva, X-linked osteoporosis, Loeys-Diets syndrome, osteopetrosis, Erdheim-Chester disease, and Cherubism. A variety of advanced available analytical techniques were identified that may help to provide additional detail on cellular, structural, and compositional characteristics in rare bone diseases complementing classical histopathology. To date, these techniques have only been used in research and not in daily clinical practice. Clinical application of bone quality assessment techniques depends upon several aspects such as availability of the technique in hospitals, the existence of reference data, and a cooperative network of researchers and clinicians. The evaluation of rare metabolic bone disorders requires a repertoire of different methods, owing to their distinct bone tissue characteristics. The broader use of bone material obtained from biopsies could provide much more information about pathophysiology or treatment options and establish bone biopsies as a valuable tool in rare metabolic bone diseases.
Topics: Biopsy; Bone Diseases; Fibrous Dysplasia of Bone; Humans; Loeys-Dietz Syndrome; Myositis Ossificans; Osteitis Deformans; Osteogenesis Imperfecta; Osteopetrosis; Osteoporosis; Rare Diseases
PubMed: 32714279
DOI: 10.3389/fendo.2020.00399 -
Frontiers in Endocrinology 2020Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events,...
Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and NO-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described.
Topics: Adult; Amputation, Surgical; Female; Humans; Leg; Myositis Ossificans; Treatment Outcome
PubMed: 32973683
DOI: 10.3389/fendo.2020.00570