Palindromický revmatismus (PR) je klinický syndrom charakterizovaný opětovnými epizodami vzplanutí bolesti, otoku a zarudnutí kloubu/ů a přilehlých tkání s kompletní remisí bez zbytkového poškození. Ultrasonografickým zobrazováním se zjistilo, že u těchto epizod jde hlavně o extrakapsulární zánět. Epizodická vzplanutí jsou u PR zpravidla monoartikulární a postihují nejčastěji tytéž klouby jako revmatoidní artritida (RA), tj. hlavně proximální interfalangeální, metakarpofalangeální a zápěstní klouby. Klinická zkušenost nabízí hodnotit PR jako neobvyklou vstupní formu RA. Genotypové studie, recentně zvláště sekvenování kompletního exomu, však ukázaly rozdíly mezi PR a RA; u části PR byla zjištěna také mutace MEFV genu. Nejčastější prognózou PR je vyústění do RA; platí to hlavně pro PR s protilátkami proti citrulinovaným peptidům. Konečnou diagnózou u PR ale může být i jiné systémové autoimunitní revmatické onemocnění, např. systémový lupus erythematodes. Rekurentní zánětlivá vzplanutí mohou přetrvávat beze změny i po léta, nebo naopak dojde k dlouhodobé remisi, ale opětovné vzplanutí se nedá vyloučit. Terapie PR napodobuje léčbu RA; úspěšnou blokaci rekurencí extrakapsulárního zánětu u PR je možné hodnotit obdobně jako léčebné „okno příležitosti“ u RA.
Palindromic rheumatism (PR) is a clinical syndrome characterized by recurrent, transient episodes of joint pain, erythema, and swelling, typically without resulting in permanent joint damage. Ultrasonographic studies have shown that extra-capsular inflammation is a distinctive feature of this condition. PR flares are frequently monoarticular and commonly involve joints also affected in rheumatoid arthritis (RA), particularly the proximal interphalangeal, metacarpophalangeal, and wrist joints. Although clinical experience has long suggested that PR may represent an atypical form or precursor of RA, recent genetic analyses, particularly whole-exome sequencing, have revealed notable distinctions between the two diseases. In some patients with PR, mutations in the MEFV gene have been identified, further supporting its heterogeneous nature. RA remains the most frequent definitive diagnosis in patients with PR, especially in those positive for anti-citrullinated peptide antibodies. However, a subset of PR cases may evolve into other systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus. In many patients, PR persists for years with recurrent flares or may enter remission, which may be prolonged but not necessarily permanent. Lifelong monitoring is essential, as flares can recur unpredictably. Management strategies for PR often mirror those of RA. Early and effective suppression of extra-capsular inflammation during PR flares may be as crucial as the "window of opportunity" concept in RA, potentially influencing long-term outcomes
- Keywords
- palindromický revmatismus,
- MeSH
- Genotype MeSH
- Humans MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Prospective Studies MeSH
- Rheumatic Diseases * diagnosis drug therapy pathology MeSH
- Arthritis, Rheumatoid MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.
- MeSH
- Adalimumab therapeutic use MeSH
- Spondylitis, Ankylosing * drug therapy mortality MeSH
- Antirheumatic Agents * therapeutic use MeSH
- Adult MeSH
- Etanercept * therapeutic use MeSH
- Infliximab therapeutic use MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Arthritis, Psoriatic * drug therapy mortality MeSH
- Registries * MeSH
- Arthritis, Rheumatoid * drug therapy mortality MeSH
- Aged MeSH
- Propensity Score * MeSH
- Tumor Necrosis Factor-alpha * antagonists & inhibitors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
Biologická a cílená léčba zásadně proměnila terapeutický přístup k pacientům se zánětlivými revmatickými onemocněními, mezi něž patří revmatoidní artritida (RA), axiální spondyloartritidy (axSpA), psoriatická artritida (PsA) a nověji také systémový lupus erythematodes (SLE) či systémová sklerodermie (SSc). Díky cílené modulaci klíčových struktur imunitní odpovědi vykazují biologická léčiva ve srovnání s konvenčními syntetickými chorobu-modifikujícími antirevmatiky (csDMARDs) vyšší terapeutickou účinnost a často i příznivější bezpečnostní profil. Biologická a cílená syntetická terapie však není prostá rizik. Spektrum a charakter nežádoucích účinků se v mnoha ohledech liší od tradičních imunosupresiv a vyžadují specifický přístup v rámci monitorace a komplexní strategie léčby. Tento přehledový článek se zaměřuje na bezpečnostní profil všech v současnosti dostupných biologických a cílených syntetických DMARDs (bDMARDs, tsDMARDs) používaných v terapii zánětlivých revmatických onemocnění, a to s důrazem na jejich praktické uplatnění. Mezi tyto léčivé přípravky patří inhibitory TNFα, inhibitory IL-6, blokátory kostimulačního signálu, anti-CD20 protilátky, inhibitory IL-17, IL-23, IL-12/23, inhibitory BLYS a léčiva cílená na interferony typu I. Znalost potenciálních nežádoucích účinků a jejich včasná identifikace a řešení představují základní předpoklad úspěšné, bezpečné a dlouhodobě udržitelné biologické léčby v klinické praxi.
Biological and targeted synthetic agents have fundamentally transformed the therapeutic approach to patients with inflammatory rheumatic diseases, including rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and more recently also systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). By targeting key components of the immune response, biologic therapies demonstrate superior efficacy and often a more favorable safety profile compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). However, biologic and targeted synthetic therapies are not without risks. The spectrum and nature of adverse events differ substantially from those associated with traditional immunosuppressants and require specific strategies for monitoring and management. This review focuses on the safety profiles of all currently available biological and targeted synthetic DMARDs (bDMARDs, tsDMARDs) used in the treatment of inflammatory rheumatic diseases, with an emphasis on practical clinical application. These agents include TNFα inhibitors, IL-6 inhibitors, co-stimulation blockers, anti-CD20 monoclonal antibodies, IL-17, IL-23, and IL-12/23 inhibitors, as well as agents targeting B-lymphocyte stimulator (BLYS) and type I interferons. Awareness of potential adverse effects, along with timely identification and management, are essential prerequisites for the safe, effective, and sustainable use of biologic therapies in clinical practice.
- MeSH
- Antirheumatic Agents pharmacology classification adverse effects therapeutic use MeSH
- Biological Therapy * methods adverse effects MeSH
- Interleukin-6 Inhibitors pharmacology classification adverse effects therapeutic use MeSH
- Janus Kinase Inhibitors pharmacology adverse effects therapeutic use MeSH
- Tumor Necrosis Factor Inhibitors pharmacology classification adverse effects therapeutic use MeSH
- Interleukin-17 antagonists & inhibitors MeSH
- Humans MeSH
- Rheumatic Diseases * drug therapy MeSH
- Rituximab pharmacology adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
PURPOSE: Surgical mesh, often made from polypropylene, is commonly recommended to enhance hernia repair outcomes in adults. Concerns about polypropylene, as a cause of allergy and/or autoimmune disease prompted this study to evaluate immunological parameters in patients with mesh and healthy controls. METHODOLOGY: A case-control cohort study was conducted at a university hospital. Electronic patient records of hernia repairs using polypropylene mesh (January 2018-April 2022) were analysed. Blood samples from patients and healthy controls were assessed using various methods, including enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunoblotting, and flow cytometry. RESULTS: The database search identified 1544 participants. After applying the exclusion criteria 33 patients remained in the polypropylene mesh group. Patients with mesh had lower median IgG3 levels (p = 0.02) and Rheumatoid factor (RF) IgM (p = 0.018) compared to the control group. Although both IgG3 and RF IgM levels were in the normal reference range. In addition, 5 patients in the mesh group tested positive for serum ANCA levels compared to none in the control group (p = 0.053). No other differences in immunoglobulins, autoantibodies, complement, or immune cell subtypes were observed. CONCLUSION: Patients with polypropylene mesh exhibited median IgG3 and RF IgM serum levels that were within the normal reference range but slightly lower compared to the control group. Among patients with polypropylene mesh, five displayed positive serum ANCA levels without autoimmune-related symptoms. Overall, no definitive signs of autoimmunity caused by polypropylene mesh. A larger, prospective study is warranted to further explore potential immune responses to polypropylene mesh.
- MeSH
- Surgical Mesh * adverse effects MeSH
- Adult MeSH
- Immunoglobulin G blood MeSH
- Immunoglobulin M blood MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Herniorrhaphy * instrumentation MeSH
- Polypropylenes * adverse effects MeSH
- Rheumatoid Factor blood MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.
- MeSH
- Flavonoids * pharmacology chemistry therapeutic use metabolism MeSH
- Humans MeSH
- Neoplasms drug therapy metabolism pathology MeSH
- Neurodegenerative Diseases drug therapy metabolism MeSH
- Oxidative Stress * drug effects MeSH
- Inflammation * drug therapy metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: To our knowledge, limited information is available about the differences in the characteristics of rheumatoid factor (RF)-negative polyarticular juvenile idiopathic arthritis (JIA) throughout the world. This study was aimed to compare the demographic and clinical features of patients with RF-negative polyarthritis across the world. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment regimens, and disease status in patients from different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and collection of ongoing medications. RESULTS: Among the 9081 patients enrolled in the EPOCA study, 2141 patients (23.6%) with RF-negative polyarthritis were included in the present analysis. The prevalence of RF-negative polyarthritis was highest in North America and lowest in Southeast Asia (12.7%). The age at disease onset was lower in Northern and Southern Europe, where the highest prevalence of uveitis was found. Uveitis was rare in Southeast Asia, Africa & Middle East and Latin America. Patients from Eastern Europe, Latin America and Africa and Middle East presented with the highest prevalence of active joints at the visit. The combination of early onset, ANA positivity, and uveitis was observed mainly in Southern Europe (39%). CONCLUSIONS: Our results confirm the wide heterogeneity of the clinical presentation and outcome of children with RF-negative polyarticular JIA throughout the world. In particular, relevant differences in the onset age were observed across geographic areas. The group of children with early onset polyarthritis, ANA positivity, and risk of uveitis is remarkably frequent in Southern Europe.
- MeSH
- Antirheumatic Agents therapeutic use MeSH
- Global Health MeSH
- Child MeSH
- Arthritis, Juvenile * epidemiology diagnosis MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Prevalence MeSH
- Cross-Sectional Studies MeSH
- Retrospective Studies MeSH
- Rheumatoid Factor * blood MeSH
- Uveitis epidemiology diagnosis MeSH
- Age of Onset MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
- MeSH
- Acetazolamide therapeutic use MeSH
- Biological Therapy methods adverse effects MeSH
- Adrenal Cortex Hormones therapeutic use MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Arthritis, Juvenile * drug therapy complications MeSH
- Cataract drug therapy complications therapy MeSH
- Humans MeSH
- Methotrexate adverse effects therapeutic use MeSH
- Therapeutic Occlusion methods MeSH
- Child, Preschool MeSH
- Disease Progression MeSH
- Risk MeSH
- Uveitis * diagnosis drug therapy complications pathology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Case Reports MeSH
Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
- MeSH
- Spondylitis, Ankylosing blood diagnosis immunology MeSH
- Axial Spondyloarthritis blood diagnosis MeSH
- Biomarkers * blood MeSH
- C-Reactive Protein analysis metabolism MeSH
- HLA-B27 Antigen genetics immunology MeSH
- Inflammatory Bowel Diseases * blood immunology diagnosis complications MeSH
- Leukocyte L1 Antigen Complex blood MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
- MeSH
- Biomarkers blood MeSH
- Cytokines blood MeSH
- Adult MeSH
- Glucocorticoids * administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Inflammation Mediators * blood metabolism MeSH
- Arthritis, Rheumatoid * drug therapy blood immunology MeSH
- Aged MeSH
- Inflammation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH