-
Arthritis & Rheumatology (Hoboken, N.J.) Apr 2022To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ)...
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
OBJECTIVE
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
METHODS
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
CONCLUSION
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Topics: Arthritis, Juvenile; Humans; Quality of Life; Rheumatology; Temporomandibular Joint; Temporomandibular Joint Disorders; United States; Uveitis
PubMed: 35233993
DOI: 10.1002/art.42037 -
Arthritis Care & Research Apr 2022To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ)...
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
OBJECTIVE
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
METHODS
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
CONCLUSION
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Glucocorticoids; Humans; Quality of Life; Rheumatology; Temporomandibular Joint; Temporomandibular Joint Disorders; United States; Uveitis
PubMed: 35233986
DOI: 10.1002/acr.24853 -
Frontiers in Immunology 2022Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that...
Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.
Topics: Endoplasmic Reticulum Stress; Epithelial Cells; Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Nephrolithiasis; Reactive Oxygen Species
PubMed: 35154136
DOI: 10.3389/fimmu.2022.818625 -
Cureus Oct 2021Among the autoimmune (AI) diseases, systemic lupus erythematosus (SLE) is known to mimic various disease processes and this can lead to under-diagnosis of macrophage... (Review)
Review
Among the autoimmune (AI) diseases, systemic lupus erythematosus (SLE) is known to mimic various disease processes and this can lead to under-diagnosis of macrophage activation syndrome (a dire complication). We aimed at performing a systematic review to identify trigger factors that could lead to the development of macrophage activation syndrome (MAS) in patients with SLE as well as identify factors that can affect mortality. We searched the following databases to extract relevant articles: PubMed, ScienceDirect, Cochrane library, Pro-Quest, and Google Scholar. We used search terms including but not limited to hemophagocytic syndromes OR hemophagocytic lymphohistiocytosis OR macrophage activation syndrome OR HLH OR secondary hemophagocytic lymphohistiocytosis AND systemic lupus erythematosus OR SLE. We screened the articles first by titles and abstracts and later by full text. After the application of our eligibility criteria, we identified eight studies to include in our final synthesis. The studies showed that lupus flare itself, as well as, time to onset and high systemic lupus erythematosus disease activity index (SLEDAI) scores, were major risk factors that led to the development of MAS. In addition, infections followed by drugs, underlying malignancy, and pregnancy were other potential trigger factors identified. Studies also detected that MAS development led to high intensive care unit (ICU) admissions and in-hospital mortalities with C-reactive protein (CRP) levels, age, presence of infection, leukopenia, thrombocytopenia, MAS throughout the hospital stay, and high liver function tests (LFTs) as signs of poor prognosis. Additionally, ferritin levels, LFTs, and triglyceride levels formed an important part of diagnostic criteria. However, our review was limited due to the absence of prospective studies and heterogeneity in the studies seen. More studies need to be done to identify various factors leading to hemophagocytic lymphohistiocytosis (HLH) in autoimmune diseases with validated criteria for MAS secondary to autoimmune diseases.
PubMed: 34804679
DOI: 10.7759/cureus.18822 -
Clinical Immunology (Orlando, Fla.) Sep 2021The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate...
INTRODUCTION
The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe COVID-19, however clinical outcome data is inconclusive.
OBJECTIVE
To evaluate the clinical outcomes of BTK inhibitors (BTKinibs) in patients with COVID-19.
EVIDENCE REVIEW
We searched PubMed, Embase, and Web of Science:Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.
FINDINGS
125 articles were identified, 6 of which met inclusion criteria. The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs.
CONCLUSIONS AND RELEVANCE
BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration.
PubMed: 34352390
DOI: 10.1016/j.clim.2021.108816 -
Frontiers in Medicine 2021Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not...
Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not considered as a frequent complication of pSLE; however, its occurrence could be under-estimated and the diagnosis can be challenging. In order to address this issue, we performed a systematic review of the available medical literature, aiming to retrieve all those papers providing diagnostic (clinical/laboratory) data on patients with pSLE-related MAS, in individual or aggregated form. The selected case reports and series provided a pool of 46 patients, accounting for 48 episodes of MAS in total. We re-analyzed these patients in light of the diagnostic criteria for MAS validated in systemic Juvenile Idiopathic Arthritis (sJIA) patients and the preliminary diagnostic criteria for MAS in pSLE, respectively. Five clinical studies were also selected and used to support this analysis. This systematic review confirms that MAS diagnosis in pSLE patients is characterized by several diagnostic challenges, which could lead to delayed diagnosis and/or under-estimation of this complication. Specific criteria should be considered to diagnose MAS in different rheumatic diseases; as regards pSLE, the aforementioned preliminary criteria for MAS in pSLE seem to perform better than the sJIA-related MAS criteria, because of a lower ferritin cut-off.
PubMed: 34150813
DOI: 10.3389/fmed.2021.681875 -
Research Square Mar 2021ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against...
ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.
PubMed: 33791689
DOI: 10.21203/rs.3.rs-319342/v1 -
Journal of Musculoskeletal & Neuronal... Mar 2021Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown.
METHODS
To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG's PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores.
RESULTS
The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma.
CONCLUSIONS
This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Neoplasms; Databases, Genetic; Gene Regulatory Networks; Humans; Immunity, Cellular; Macrophages; Osteosarcoma; Prognosis; Protein Array Analysis; Receptors, Cell Surface; Tumor Microenvironment
PubMed: 33657763
DOI: No ID Found -
SN Comprehensive Clinical Medicine 2021With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are...
UNLABELLED
With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries ( < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C.
SUPPLEMENTARY INFORMATION
The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.
PubMed: 33432304
DOI: 10.1007/s42399-020-00690-6 -
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