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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 -
Sarcoidosis, Vasculitis, and Diffuse... Mar 2024Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent...
BACKGROUND AND AIM
Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent manifestation of ASSD and is closely associated with morbidity and mortality, few studies have been conducted on its characteristics on high-resolution computed tomography (HRCT). In this study, we clarified the HRCT findings in patients with anti-ARS antibody-positive ILD (ARS-ILD). Methods: The HRCT findings at the time of the ILD diagnosis in 24 ARS-ILD patients were retrospectively evaluated by 2 pulmonologists and one radiologist. We also assessed the clinical symptoms, physical examination findings, and laboratory data including the type of anti-ARS antibodies. For a further analysis, the data of patients were divided into two groups: the polymyositis (PM)/dermatomyositis (DM) group and the non-PM/DM group.
RESULTS
The ratio of men to women was almost 1:1. The median age at the time of the diagnosis was 53 years old. Anti-glycyl (anti-EJ) and anti-histidyl (anti-Jo-1) antibodies were more common than others. An analysis of the HRCT patterns of 23 ARS-ILD patients showed that the most common pattern was the nonspecific interstitial pneumonia (NSIP) pattern. The second most common pattern was the usual interstitial pneumonia (UIP) pattern. Between the PM/DM and non-PM/DM groups, no clear trends were noted in the age, sex ratio, proportion of HRCT patterns, or type of anti-ARS antibodies.
CONCLUSIONS
This retrospective study demonstrated that ARS-ILD patients, regardless of myositis symptoms, most often showed the NSIP pattern on HRCT, as previously reported. However, unlike previous reports, the UIP pattern on HRCT was not rare.
PubMed: 38567566
DOI: 10.36141/svdld.v41i1.14144 -
Frontiers in Immunology 2024Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically...
Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
BACKGROUND
Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement.
METHODS
Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels.
RESULTS
Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls.
CONCLUSION
This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
Topics: Humans; Antibodies, Antinuclear; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Dermatomyositis; Killer Cells, Natural; Lupus Erythematosus, Systemic; Lupus Nephritis; Receptors, Tumor Necrosis Factor, Type I
PubMed: 38562920
DOI: 10.3389/fimmu.2024.1327255 -
Journal of Medical Case Reports Apr 2024To our knowledge, there is no previous report in the literature of non-traumatic neglected complete cervical spine dislocation characterized by anterior spondyloptosis...
BACKGROUND
To our knowledge, there is no previous report in the literature of non-traumatic neglected complete cervical spine dislocation characterized by anterior spondyloptosis of C4, extreme head drop, and irreducible cervicothoracic kyphosis.
CASE PRESENTATION
We report the case of a 33-year-old Caucasian man with a 17-year history of severe immune polymyositis and regular physiotherapy who presented with severe non-reducible kyphosis of the cervicothoracic junction and progressive tetraparesia for several weeks after a physiotherapy session. Radiographs, computed tomography, and magnetic resonance imaging revealed a complete dislocation at the C4-C5 level, with C4 spondyloptosis, kyphotic angulation, spinal cord compression, and severe myelopathy. Due to recent worsening of neurological symptoms, an invasive treatment strategy was indicated. The patient's neurological status and spinal deformity greatly complicated the anesthetic and surgical management, which was planned after extensive multidisciplinary discussion and relied on close collaboration between the orthopedic surgeon and the anesthetist. Regarding anesthesia, difficult airway access was expected due to severe cervical angulation, limited mouth opening, and thyromental distance, with high risk of difficult ventilation and intubation. Patient management was further complicated by a theoretical risk of neurogenic shock, motor and sensory deterioration, instability due to position changes during surgery, and postoperative respiratory failure. Regarding surgery, a multistage approach was carefully planned. After a failed attempt at closed reduction, a three-stage surgical procedure was performed to reduce displacement and stabilize the spine, resulting in correct spinal realignment and fixation. Progressive complete neurological recovery was observed.
CONCLUSION
This case illustrates the successful management of a critical situation based on a multidisciplinary collaboration involving radiologists, anesthesiologists, and spine surgeons.
Topics: Male; Humans; Adult; Cervical Vertebrae; Spinal Cord Compression; Spinal Injuries; Radiography; Kyphosis
PubMed: 38556889
DOI: 10.1186/s13256-024-04446-x -
Tomography (Ann Arbor, Mich.) Mar 2024(1) Background: The intravoxel incoherent motion (IVIM) model can provide information about both molecular diffusion and blood flow for the evaluation of skeletal muscle...
(1) Background: The intravoxel incoherent motion (IVIM) model can provide information about both molecular diffusion and blood flow for the evaluation of skeletal muscle inflammation. MRI-based fat quantification is advantageous for assessing fat infiltration in skeletal muscle. (2) Purpose: We aimed to quantitatively measure various parameters associated with IVIM diffusion-weighted imaging (DWI) and fat quantification in the muscles of patients with polymyositis and dermatomyositis using magnetic resonance imaging and to investigate the relationship between these parameters and electromyography (EMG) findings. (3) Material and methods: Data were retrospectively evaluated for 12 patients with polymyositis and dermatomyositis who underwent thigh MRI, including IVIM-DWI and fat quantification. The IVIM-derived parameters included the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (). Fat fraction values were assessed using the six-point Dixon technique. Needle EMG was performed within 9 days of the MRI. (4) Results: The values (19.02 ± 4.87%) in muscles with pathological spontaneous activity on EMG were significantly higher than those (14.60 ± 5.31) in muscles without pathological spontaneous activity ( < 0.027). There were no significant differences in D, D*, ADC, or fat fraction between muscles with and without pathologic spontaneous activity. Significant negative correlations were observed between fat fraction and amplitude ( = -0.402, < 0.015) and between fat fraction and duration ( = -0.360, < 0.031). (5) Conclusion: The current study demonstrates that IVIM-DWI and fat quantification using 3.0 T MRI may aid in predicting EMG findings in patients with polymyositis and dermatomyositis and promote the pathophysiological study of idiopathic inflammatory myopathies.
Topics: Humans; Electromyography; Dermatomyositis; Retrospective Studies; Diffusion Magnetic Resonance Imaging; Polymyositis; Myositis
PubMed: 38535771
DOI: 10.3390/tomography10030029 -
Frontiers in Immunology 2024Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of...
OBJECTIVE
Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.
METHODS
This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.
RESULTS
Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4 T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8 T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8 T cells and multiple cytokines than Endotype1.
CONCLUSION
Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
Topics: Humans; Interferon-Induced Helicase, IFIH1; Dermatomyositis; CD8-Positive T-Lymphocytes; Viremia; Lung Diseases, Interstitial; Cytomegalovirus Infections
PubMed: 38533498
DOI: 10.3389/fimmu.2024.1349611 -
Anais Brasileiros de Dermatologia 2024Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes...
BACKGROUND
Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes clinical diagnosis and treatment of DM very challenging.
OBJECTIVES
Unsupervised classification in DM patients and analysis of key factors related to clinical outcomes.
METHODS
This retrospective study was conducted between 2017 and 2022 at the Department of Rheumatology, Xiangya Hospital, Central South University. 162 DM patients were enrolled for unsupervised hierarchical cluster analysis. In addition, we divided the clinical outcomes of DM patients into four subgroups: withdrawal, stabilization, aggravation, and death, and compared the clinical profiles amongst the subgroups.
RESULTS
Out of 162 DM patients, three clusters were defined. Cluster 1 (n = 40) was mainly grouped by patients with prominent muscular involvement and mild Interstitial Lung Disease (ILD). Cluster 2 (n = 72) grouped patients with skin rash, anti-Melanoma Differentiation Associated protein 5 positive (anti-MDA5), and Rapid Progressive Interstitial Lung Disease (RP-ILD). Cluster 3 (n = 50) grouped patients with the mildest symptoms. The proportion of death increased across the three clusters (cluster 3 < cluster 1 < cluster 2).
STUDY LIMITATIONS
The number of cases was limited for the subsequent construction and validation of predictive models. We did not review all skin symptoms or pathological changes in detail.
CONCLUSIONS
We reclassified DM into three clusters with different risks for poor outcome based on diverse clinical profiles. Clinical serological testing and cluster analysis are necessary to help clinicians evaluate patients during follow-up and conduct phenotype-based personalized care in DM.
Topics: Humans; Dermatomyositis; Female; Retrospective Studies; Male; Middle Aged; Phenotype; Adult; Cluster Analysis; Aged; Lung Diseases, Interstitial; Serologic Tests; Outcome Assessment, Health Care; Autoantibodies; Interferon-Induced Helicase, IFIH1; Severity of Illness Index
PubMed: 38522973
DOI: 10.1016/j.abd.2023.06.005 -
Cureus Feb 2024The sigmoid colon is an uncommon site for the origin of primary malignant lymphomas in the GI tract. Additionally, immunosuppressive agents, widely used in treating...
The sigmoid colon is an uncommon site for the origin of primary malignant lymphomas in the GI tract. Additionally, immunosuppressive agents, widely used in treating autoimmune diseases, have been associated with the induction of malignancies, including lymphoproliferative disorders. In this report, we present a rare case of GI perforation suggesting a link between immunosuppressive therapy, particularly tacrolimus treatment, and diffuse large B-cell lymphoma (DLBCL). A 75-year-old female patient presented with abdominal pain to our ER. She had a medical history of polymyositis and interstitial pneumonia, treated with the immunosuppressant tacrolimus. An abdominal CT scan revealed free gas in the abdominal cavity, leading to a diagnosis of GI perforation. The patient exhibited generalized peritonitis and underwent emergency surgery the same day. During surgery, a perforation in the sigmoid colon was identified, and a Hartmann procedure was performed. Postoperative pathology showed CD20+, CD30+, CD5-, CD10-, BCL6+, MUM1+, and MIB-1 LI of 50-60%. The diagnosis of DLBCL was confirmed, classified as EBV-positive diffuse large B-cell lymphoma, not otherwise specified (NOS), in the sigmoid colon, with positive EBER-ISH, LMP-1, and EBNA2 findings. Given her history of immunosuppressant use, she was categorized as having other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), according to the WHO Classification of 2017. This case highlights the importance for clinicians to consider the risk of oncogenesis associated with the prolonged use of immunosuppressive agents.
PubMed: 38516454
DOI: 10.7759/cureus.54571 -
Anti-SAE dermatomyositis: clinical and histologic characteristics from a monocentric Italian cohort.Clinical and Experimental Rheumatology Feb 2024Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered...
OBJECTIVES
Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered the least studied subset. Our study aimed to evaluate the clinical and histological characteristics of DM patients with anti-SAE antibodies. As reference, patients with anti-Mi2 antibodies associated DM, representing a well-characterised subset, were analysed.
METHODS
We recorded data from our DM cohort in the INflammatory MYositis REgistry (INMYRE). Patients were divided into two groups: those positive for anti-SAE and those positive for anti-Mi2 antibodies. Clinical characteristics, including skin, muscle, and extra-muscular involvements, were recorded. Available muscle biopsies were compared between the two groups.
RESULTS
Of 92 DM patients, 10 (10.9%) were positive for anti-SAE and 17 (18.5%) for anti-Mi2. Anti-SAE positive DM patients showed classic DM findings but were characterised by a higher prevalence of skin itching (60% vs. 11.8%, p<0.01), shawl sign (40% vs. 5.9%, p<0.05) and lung involvement (30% vs. 0%, p<0.05) compared to anti-Mi2 positive patients. Furthermore, anti-SAE positive DM patients showed lower creatine kinase levels than those with anti-Mi2 (median [IQR]: 101 [58-647] vs. 1984 [974-3717], p<0.05) and a lower percentage of muscle fibre degeneration and necrosis (1.5%±1.7 vs. 5.9%±3.2, p<0.05) in muscle biopsies. No other differences were observed.
CONCLUSIONS
Anti-SAE DM represents a disease subset characterised by classic cutaneous involvement often associated with itching, less severe muscle involvement, but potential pulmonary involvement that should always be investigated in these patients.
Topics: Humans; Dermatomyositis; Autoantibodies; Myositis; Pruritus; Italy
PubMed: 38488098
DOI: 10.55563/clinexprheumatol/110r0p -
Clinical and Experimental Rheumatology Feb 2024To investigate the prevalence and characteristics of typical polymyositis (PM) in Chinese patients with idiopathic inflammatory myopathy (IIM).
OBJECTIVES
To investigate the prevalence and characteristics of typical polymyositis (PM) in Chinese patients with idiopathic inflammatory myopathy (IIM).
METHODS
Patients diagnosed with IIM according to the 2017 EULAR/ACR criteria were included. Serological aspects including myositis-specific antibodies (MSA) and pathological data were re-evaluated. The diagnosis of typical PM was strictly done using the pathological criteria, while excluding other IIM subtypes such as dermatomyositis (DM), immune-mediated necrotising myopathies (IMNM), anti-synthetase syndrome (ASS), and sporadic inclusion body myositis (sIBM), based on their respective diagnostic criteria.
RESULTS
A total of 544 IIM patients with muscle biopsy were involved, and 129 of them were diagnosed with initial PM according to the 2017 EULAR/ACR criteria. Only 6 (1.1%, 6/544) patients met the strict definition of typical PM after re-evaluation. Patients with typical PM were MSA-negative (100% vs. 35.7%, p=0.003) and had CD8+ T cells surrounding or invading non-necrotic muscle fibres in muscle biopsies (100% vs. 7.8%, p<0.001) compared to the initially diagnosed PM patients. All typical PM patients achieved clinical remission at the second-year follow-up. Typical PM patients had a favourable prognosis compared to MSA-negative IMNM and unspecific myositis patients.
CONCLUSIONS
Strictly defined typical PM is a rare clinical subtype in Chinese IIM patients. Typical PM patients with classical pathology were MSA-negative and responded well to treatment and had a favourable prognosis. It is crucial for clinicians to combine clinical, serological, and pathological features to properly distinguish PM from other IIM subtypes.
Topics: Humans; Myositis; Polymyositis; Myositis, Inclusion Body; Antibodies; Autoimmune Diseases; China; Autoantibodies
PubMed: 38488095
DOI: 10.55563/clinexprheumatol/7v9d2x