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Journal of Orthopaedic Surgery and... Mar 2023Immune-mediated conditions associated to Corona Virus Disease-19 (COVID-19) have been reported, including vasculitis, antiphospholipid antibody syndrome, myositis, and... (Review)
Review
BACKGROUND
Immune-mediated conditions associated to Corona Virus Disease-19 (COVID-19) have been reported, including vasculitis, antiphospholipid antibody syndrome, myositis, and lupus. Emerging studies have reported the potential occurrence of reactive arthritis in patients previously infected with COVID-19. This systematic review summarised the current evidence on the occurrence of reactive arthritis in patients previously infected by COVID-19.
METHODS
This study was conducted according to the 2020 PRISMA guidelines. All the clinical investigations describing the occurrence of reactive arthritis following COVID-19 were accessed. In September 2022, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. The generalities of the study were extracted: author, year and journal of publication, country of the main author, study design, sample size, mean age, number of women, main results of the study. The following data on COVID-19 severity and management were retrieved: type of treatment, hospitalization regimes (inpatient or outpatient), admission to the intensive care unit, need of mechanical ventilation, pharmacological management. The following data on reactive arthritis were collected: time elapsed between COVID-19 infection to the onset of reactive arthritis symptoms (days), pharmacological management, type of arthritis (mono- or bilateral, mono- or polyarticular), extra-articular manifestations, presence of tenosynovitis or enthesitis, synovial examination at microscopic polarised light, imaging (radiography, magnetic resonance, sonography), clinical examination, laboratory findings.
RESULTS
Data from 27 case reports (54 patients) were retrieved, with a mean age of 49.8 ± 14.5 years. 54% (29 of 54 patients) were women. The mean time span between COVID-19 infection and the occurrence of reactive arthritis symptoms was 22.3 ± 10.7 days. Between studies diagnosis and management of reactive arthritis were heterogeneous. Symptoms resolved within few days in all studies considered. At last follow-up, all patients were minimally symptomatic or asymptomatic, and no additional therapy or attentions were required by any patient.
CONCLUSION
Poor evidence suggests that COVID-19 could target the musculoskeletal system causing reactive arthritis at its post infectious stage. COVID-19 can act as a causative agent or as a trigger for development of reactive arthritis even without presence of antibodies of rheumatological disorders. Treating physicians should have a high index of suspicion while treating post infectious COVID-19 patient with arthralgia.
LEVEL OF EVIDENCE
Level IV, systematic review.
Topics: Humans; Female; Adult; Middle Aged; Male; COVID-19; SARS-CoV-2; Arthritis, Reactive; Inpatients; Antibodies; COVID-19 Testing
PubMed: 36922870
DOI: 10.1186/s13018-023-03651-6 -
Vaccines Oct 2023A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking.... (Review)
Review
A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking. Therefore, we investigated the demographics, management, and prognosis of new R-IMIDs in adults following SARS-CoV-2 vaccinations. A systematic literature search of Medline, Embase, Google Scholar, LitCovid, and Cochrane was conducted. We included any English-language study that reported new-onset R-IMID in adults following the post-COVID-19 vaccination. A total of 271 cases were reported from 39 countries between January 2021 and May 2023. The mean age of patients was 56 (range 18-90), and most were females (170, 62.5%). Most (153, 56.5%) received the Pfizer BioNTech COVID-19 vaccine. Nearly 50% of patients developed R-IMID after the second dose of the vaccine. Vasculitis was the most prevalent clinical presentation (86, 31.7%), followed by connective tissue disease (66, 24.3%). The mean duration between the vaccine's 'trigger' dose and R-IMID was 11 days. Most (220, 81.2%) received corticosteroids; however, 42% (115) received DMARDs such as methotrexate, cyclophosphamide, tocilizumab, anakinra, IV immunoglobulins, plasma exchange, or rituximab. Complete remission was achieved in 75 patients (27.7%), and 137 (50.6%) improved following the treatment. Two patients died due to myositis. This SR highlights that SARS-CoV-2 vaccines may trigger R-IMID; however, further epidemiology studies are required.
PubMed: 37896974
DOI: 10.3390/vaccines11101571 -
Rheumatology International Jul 2023A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and...
A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and the development of new-onset ACTDs. The "population" was adults with disease terms for ACTDs, including systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), anti-synthetase syndrome, mixed CTD and undifferentiated CTD, and "intervention" as COVID-19 and related terms. Databases were searched for English-language articles published until September 2022. We identified 2236 articles with 28 ultimately included. Of the 28 included patients, 64.3% were female, with a mean age was 51.1 years. The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including four dermatomyositis); 7 (25%) SLE; four (14.3%) anti-synthetase syndrome; four (14.3%) SSc; two (7.1%) other ACTD (one lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) had lupus nephritis. The average time from COVID-19 to ACTD diagnosis was 23.7 days. A third of patients were admitted to critical care, one for treatment of haemophagocytic lymphohistiocytosis in SLE (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. 80% of patients went into remission of ACTD following treatment, while three (10%) patients died-one due to macrophage activation syndrome with anti-synthetase syndrome and two from unreported causes. Our results suggest a potential association between COVID-19 and new-onset ACTDs, notably in young females, reflecting more comprehensive CTD epidemiology. The most common diagnosis in our cohort was IIM. The aetiology and mechanisms by which ACTDs emerge following COVID-19 remain unknown and require further research.
Topics: Adult; Humans; Female; Middle Aged; Male; Mixed Connective Tissue Disease; Incidence; COVID-19; Connective Tissue Diseases; Autoimmune Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Prognosis; Lupus Nephritis; Myositis
PubMed: 36786873
DOI: 10.1007/s00296-023-05283-9 -
Frontiers in Neurology 2022Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase use of ICIs, incidence of nirAEs is...
BACKGROUND
Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase use of ICIs, incidence of nirAEs is growing, among which ICI related MG (irMG) is causing high fatality rate. Given the limited evidence, data from a large cohort of patients with irMG is needed to aid in recognition and management of this fatal complication.
OBJECTIVE
This study aimed to summarize clinical characteristics of irMG and explore predictors of irMG clinical outcome.
METHODS
We summarized our institution's patients who were diagnosed as irMG between Sep 2019 and Oct 2021. We systematically reviewed the literature through Oct 2021 to identify all similar reported patients who met inclusion criteria. As the control group, patients with idiopathic MG were used. We collected data on clinical features, management, and outcomes of both irMG and idioMG cases. Further statistical analysis was conducted.
RESULTS
Sixty three irMG patients and 380 idioMG patients were included in the final analysis. For irMG patients, six were from our institution while the rest 57 were from reported cases. The average age of irMG patients is 70.16 years old. Forty three were male. Average time from first ICI injection to symptom onset was 5.500 weeks. Eleven patients had a past history of MG. Higher MGFA classification and higher QMGS rates were observed in irMG patients compared to idioMG patients. For complication, more irMG patients had myositis or myocarditis overlapping compared to idioMG patients. The most commonly used treatment was corticosteroids for both idioMG and irMG. Twenty one patients (35%) with irMG had unfavorable disease outcome. Single variate and multivariate binary logistic regression proved that association with myocarditis, high MGFA classification or QMGS rates at first visit were negatively related to disease outcome in irMG patients.
CONCLUSION
irMG is a life-threatening adverse event. irMG has unique clinical manifestations and clinical outcome compared to idioMG. When suspicious, early evaluation of MGFA classification, QMGS rates and myositis/myocarditis evaluation are recommended.
PubMed: 35463153
DOI: 10.3389/fneur.2022.858628 -
Journal of Scleroderma and Related... Oct 2022Severe digital ischemia, including digital ulcers and gangrene, is considered rare in patients with antisynthetase antibodies. This study aimed to elucidate the clinical...
OBJECTIVE
Severe digital ischemia, including digital ulcers and gangrene, is considered rare in patients with antisynthetase antibodies. This study aimed to elucidate the clinical features of antisynthetase-positive patients complicated with digital ulcers and/or gangrene using a systematic literature review and case series in a single-center cohort.
METHODS
A systematic literature review was conducted to identify reports describing antisynthetase-positive cases with digital ulcers and/or gangrene. Our cohort of consecutive patients with antisynthetase antibodies was stratified by the history of severe digital ischemia. Demographic and clinical features and outcomes in patients with severe digital ischemia identified in the systematic literature review and our cohort were compared with those in patients without severe digital ischemia in our cohort.
RESULTS
The systematic literature review revealed 12 antisynthetase-positive patients with severe digital ischemia from one case series and eight case reports. Seven (7%) of 100 patients with antisynthetase antibodies in our cohort had a record of severe digital ischemia. Severe digital ischemia was often found at presentation and was associated with the classification of systemic sclerosis with or without myositis overlap. Clinical features associated with severe digital ischemia in antisynthetase-positive patients included Raynaud's phenomenon ( < 0.001), digital pitting scars ( = 0.001), and nailfold capillary abnormality ( = 0.02). Outcomes of severe digital ischemia were generally favorable with vasodilators.
CONCLUSION
Severe digital ischemia is an overlooked complication in antisynthetase-positive patients. Antisynthetase antibodies should be measured in patients presenting with digital ulcers or gangrene, especially in those with systemic sclerosis phenotype and features associated with antisynthetase antibodies in the absence of systemic sclerosis-specific autoantibodies.
PubMed: 36211206
DOI: 10.1177/23971983221090857 -
Frontiers in Immunology 2021The effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only in isolated case reports and small series. This paper aims to review the current evidence regarding rituximab (RTX) use in the treatment of ILD related to anti-MDA5 DM (anti-MDA5 DM-ILD).
METHODS
We conducted a review by searching PubMed, Web of Science, Embase, and Cochrane for articles with information on patients with anti-MDA5 DM and RTX treatment, published until August 2021, in English language. The selected studies listed variation in chest high-resolution computed tomography (HRCT) and/or pulmonary function test (PFT) as a primary outcome, in patients with anti-MDA5 DM-related ILD after using RTX.
RESULTS
Of the 145 potentially eligible articles, 17 were selected. The information gathered from a total of 35 patients with anti-MDA5 DM-ILD was reviewed, including 13 men and 22 women. Patient age at onset was 47.60 ± 13.72 years old. A total of 11.43% (4/35) of the patients were found to have chronic ILD (C-ILD) and 88.57% (31/30) exhibited rapidly progressive ILD (RP-ILD). Most patients (29/30) had typical DM rashes. Prior to RTX administration, the majority of patients (27/35) were treated with medium- or high-dose glucocorticoids and at least one additional immunotherapeutic agent. With regard to RTX efficacy for ILD in anti-MDA5 DM, 71.43% (25/35) of the patients responded to treatment. Skin rash also improved in more than half of the patients after RTX treatment. The most common side effects were infections, reported by 37.14% (13/35) of the patients after using RTX.
CONCLUSION
As a CD20 targeting drug, RTX is a promising therapeutic tool for anti-MDA5 DM-ILD, although the risk of infections should be considered before treatment. Further prospective controlled studies are required to evaluate the optimal RTX treatment regimen.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289714, identifier CRD42021289714.
Topics: Adult; Aged; Antirheumatic Agents; Biomarkers; Dermatomyositis; Disease Management; Disease Susceptibility; Female; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Middle Aged; Molecular Targeted Therapy; Rituximab; Treatment Outcome
PubMed: 35116041
DOI: 10.3389/fimmu.2021.820163 -
Clinical and Experimental Rheumatology Feb 2022Juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogeneous group of systemic autoimmune diseases. Juvenile dermatomyositis (JDM) is the predominant form of...
OBJECTIVES
Juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogeneous group of systemic autoimmune diseases. Juvenile dermatomyositis (JDM) is the predominant form of JIIMs, and is a rare, chronic autoimmune illness characterised by symmetric, proximal muscle damages and involvement of the skin. In the last two decades, the use of monoclonal antibodies has also been expanded to JIIMs; however, there is limited evidence on use of these treatments. We assessed the efficacy/effectiveness and safety of biologic agents in JIIMs.
METHODS
A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process and Cochrane library to identify studies on biologics agents in JIIMs published in English language as full-text articles (1975 to December 2020) or conference abstracts (2000 to December 2020). Databases were searched with the key words regarding chronic myositis crossed with "biologic agents OR tocilizumab OR rituximab OR adalimumab OR infliximab OR anti-TNF OR etanercept". Of note, we did not include children, age, or age limits in the search as medical subject headings terms because we may have been able to extract a sub cohort of children from studies including both children and adults.
RESULTS
Of the 1633 retrieved publications, 18 articles were identified for a total of 165 patients. In real-world studies, definition of complete (CR) or partial response (PR) varied. JIIMs patients were most often treated with anti-TNF (88 pts); patients received etanercept (ETA), 48 patients infliximab (IFX), 4 patients received adalimumab (ADA). In other 15 patients IFX was followed by ADA. Rituximab (RTX) was used in 73 children. A single case series reported the use of abatacept (ABA) in 4 patients. Despite the reduced number of treated patients, complete response on myositis was reported in 29.6% (8/26) patients treated with at least one anti-TNF and in 38% (10/26) treated by RTX. Complete response of skin vasculitis has been reached in 33% (4/12) children on anti-TNF and in 36% on RTX (21/58). Anti-TNF agents might be efficient in treating calcinosis lesions.
CONCLUSIONS
Currently, the available evidence regarding the use of biologic treatment in JIIMs results quite limited but suggest a promising the use of anti-TNF agents and RTX in treating active JIIMs. Anti-TNF treatment might have a role in treating calcinosis. However, an overall very low quality of the available studies and multiple confounding factors hamper to suggest a treatment over another. Thus, randomised clinical trials are urgently required to attempt the optimal treatment in real-world setting.
Topics: Adalimumab; Adult; Antirheumatic Agents; Biological Products; Biological Therapy; Child; Etanercept; Humans; Infliximab; Myositis; Precision Medicine; Tumor Necrosis Factor Inhibitors
PubMed: 34905479
DOI: 10.55563/clinexprheumatol/ltrj4l -
Frontiers in Immunology 2024We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM).
METHODS
Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493.
RESULTS
According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events.
DISCUSSION
In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.
Topics: Humans; Dermatomyositis; Immunosuppressive Agents; Janus Kinase Inhibitors; Polymyositis; Skin
PubMed: 38576610
DOI: 10.3389/fimmu.2024.1382728 -
Seminars in Arthritis and Rheumatism Aug 2024Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug... (Review)
Review
Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug exposure. The spectrum of drugs causing DIDM has evolved over time, originally implicating hydroxyurea, penicillamine, and statins as causative agents. Tumor necrosis factor α inhibitors and immune checkpoint inhibitors have also been associated with such conditions. To bridge the gap between current literature and clinical practice, and therefore guide clinicians, we conducted a comprehensive review of English literature from Pubmed, EMBASE, and MEDLINE. Our analysis included demographic data, clinical features, laboratory findings, therapeutic outcomes, and extant research pertaining to the probable pathogenesis of DIDM induced by various drugs. Furthermore, we categorized the drugs involved in DIDM cases into biologics and traditional agents for subsequent statistical analysis. Over time, there has been a gradual accumulation of reported DIDM cases. A total of 69 published DIDM cases were documented in our study, among which 33 should be attributed to biologics and the remaining 36 to traditional drugs. Interestingly, 41 of all DIDM cases had a previous history of malignancies. Additionally, DIDM cases exhibited similar cutaneous and muscular manifestations to classic DM, with the exception of cases induced by hydroxyurea, which did not entail muscle damage. Positive antinuclear antibodies and anti-TIF1-γ autoantibodies have been predominantly observed in biologics-induced cases, while positive anti-TIF1-γ antibodies were merely reported in the cases that were primarily diagnosed with malignant diseases and exposed to ICIs afterwards. Anti-TIF1-γ antibodies may potentially serve as a red flag in the identification of co-existing malignant diseases in DM patients. We also provided a comprehensive summary and exploration of potential mechanisms lying behind drug-induced dermatomyositis. In conclusion, our review consolidates the current literature on DIDM, highlighting the evolving spectrum of medications and elucidating the differences in clinical manifestations, laboratory findings, and underlying mechanisms.
Topics: Dermatomyositis; Humans; Biological Products
PubMed: 38833729
DOI: 10.1016/j.semarthrit.2024.152478 -
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