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ID PMID Title PublicationDate abstract
35605432 Leurieus quinquestriatus scorpion venom ameliorates adjuvant-induced arthritis in rats: Mo 2022 May 20 Leurieus quinquestriatus (LQ) is a type of Egyptian scorpions. Prior studies have established the potential use of scorpion venoms in treating several autoimmune diseases. Therefore, the current study investigates the possible pharmacological effect of LQ venom in CFA-induced arthritis - through different mechanisms - by assessing different serum and tissue parameters. This study was divided into two phases: phase I was conducted to determine the lowest therapeutic dose of LQ scorpion venom, whereas phase II investigated the potential therapeutic effect of the chosen dose of LQ venom on induced arthritis through different mechanisms. The Wistar albino rats were divided equally and randomly into normal control group, LQ control group, arthritis control group, infliximab-treated group, and LQ-treated group. On day 20, blood and tissue samples were collected for further analysis of serum and tissue biomarkers as well as histopathological examination. The results revealed a potential therapeutic effect of LQ venom on arthritic-induced rats through a significant decrease in Rheumatoid Factor, Janus Kinase, Signal transducers and activators of transcription, Receptor activator of nuclear factor Kappa-B ligand, Tumor Necrosis Factor-alpha, Interleukin-6, Nuclear factor kappa-light-chain-enhancer of activated B cells and Malondialdehyde by 57%, 66%, 64%, 62%, 75%, 59%, 38%, and 69%, respectively as well as a significant increase in reduced glutathione, and Nuclear factor erythroid 2-related factor 2 by 102% and 360%, respectively. Histopathological examination of knee joint and spleen also revealed a substantial improvement, indicating the possible utilization of LQ venom in the treatment of rheumatoid arthritis.
34283454 Upadacitinib. 2022 Jan Upadacitinib is FDA approved for the treatment of moderate to severe rheumatoid arthritis (RA) that is unresponsive to first-line therapy. It is a second-generation selective Janus Kinase (JAK) inhibitor targeting the JAK1 enzyme. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to interprofessional team members in the management of patients with moderate to severe rheumatoid arthritis (RA) that is unresponsive to first-line therapy.
35124596 Anti-inflammatory effect of baicalin in rats with adjuvant arthritis and its autophagy- re 2022 BACKGROUND: It has been found that baicalin have anti-inflammatory effects since it reduces the elevated levels of pro-inflammatory cytokines. Meanwhile, it has also been shown that baicalin brings positive effects against rheumatoid arthritis (RA). However, little is observed on its beneficial effects on adjuvant arthritis. OBJECTIVE: To consider the anti-inflammatory influence of baicalin on adjuvant arthritis rats and its related autophagy mechanism. METHODS: In this research, there are six groups of rats, each has 10 rats in it. These groups are normal group (normal saline), model group (normal saline), dexamethasone group (0.125 mg/kg dexamethasone), low-dose baicalin group (50 mg/kg baicalin), medium-dose baicalin group (100 mg/kg baicalin) and high-dose baicalin group (200 mg/kg baicalin). The degrees of adjuvant-induced swelling in rats' feet were measured every 4 days and the arthritis scores were calculated every 7 days. The inflamed joint tissues were taken after rats were sacrificed. The rat' joints showed pathological changes, which were observed by HE staining. The relative expression levels of inflammatory factors IL-6, IL-1, IL-17, TNF-α, COX2, and COX1 in the rats' snovial tissues were detected by RT-PCR. As for the expression levels of autophagy markers Beclin1, Atg5, Atg7, Atg12, microtubule-associated protein-light chain3-II (LC3-II), Bcl-2, and Bax in the synovial tissue, they were discoverd by Western blot. RESULTS: Baicalin could significantly inhibit the inflammatory response of adjuvant arthritis rats. CONCLUSIONS: RT-PCR studies showed that the different doses of baicalin could inhibit the expression of TNF-a, IL-6, IL-1, IL-17, COX2 and COX1 in the synovial tissue (P< 0.05 or P< 0.01). Western blot studies showed that the different doses of baicalin could reduce the expression of Atg5, Atg7, Atg12, LC3-II, Beclin1 and Bcl-2 proteins, and increase the expression of Bax proteins in the synovial tissue.
30085534 Arthritis. 2022 Jan Arthritis is derived from the Greek term “disease of the joints.” It is defined as an acute or chronic joint inflammation that often co-exists with pain and structural damage.  Arthritis is not synonymous with arthralgia, which refers to pain localized to a joint, regardless of the origin of the pain (which may or may not be due to joint inflammation). Arthritis affected both the Neanderthals and ancient Egyptians, but It was not until 1886 that Dr. John K. Spencer coined the term “osteoarthritis.” More than 100 different types of arthritis have been described, the most common being osteoarthritis or degenerative arthritis which is non-inflammatory arthritis. Inflammatory arthritis can occur in several settings, and inflammation can be caused by autoimmune processes (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, etc.), crystal deposition induced inflammation (gout, pseudogout, basic calcium phosphate disease) or infections (septic arthritis, Lyme's arthritis).  Inflammatory arthritis can also accompany other autoimmune connective tissue diseases such as systemic lupus erythematosus, Sjogren syndrome, scleroderma, myositis, inflammatory bowel disease, celiac disease, etc.  The goal of this activity is to provide a general overview of the most common arthritides and briefly touch on key aspects of the different major disease types.
35385615 [Sjögren's syndrom: clinical, diagnostic and therapeutic innovations]. 2022 Apr 6 Sjögren's syndrome (SS) is a systemic autoimmune disease affecting the lacrimal and salivary glands. In up to one third of patients, SS may be complicated by potentially severe extra-glandular visceral involvement, which can be life-threatening. Diagnosis is often difficult based on a combination of clinical and biological evidence. The development of new imaging techniques can now help the clinician in his diagnostic approach. Long considered incurable, new medical and surgical treatments are being studied and are potentially promising. Paramedical management and regular physical activity are also essential and contribute to the improvement of patients' fatigue. The objective of this article is to review the main clinical manifestations as well as the diagnostic and therapeutic novelties developed in recent years.
34351609 Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Dispo 2022 Jan BACKGROUND AND OBJECTIVE: Infliximab, an anti-tumour necrosis factor (TNF)-α monoclonal antibody, has been approved in chronic inflammatory disease, including rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. This study aimed to investigate and characterise target-mediated drug disposition of infliximab and antigen mass turnover during infliximab treatment. METHODS: In this retrospective cohort of 186 patients treated with infliximab for rheumatoid arthritis, Crohn's disease or ankylosing spondylitis, trough infliximab concentrations were determined from samples collected between weeks 0 and 22 after treatment initiation. Target-mediated pharmacokinetics of infliximab was described using target-mediated drug disposition modelling. Target-mediated elimination parameters were determined for rheumatoid arthritis and Crohn's disease, assuming ankylosing spondylitis with no target-mediated elimination. RESULTS: The quasi-equilibrium approximation of a target-mediated drug disposition model allowed a satisfactory description of infliximab concentration-time data. Estimated baseline TNF-α amounts were similar in Crohn's disease and rheumatoid arthritis (R0 = 0.39 vs 0.46 nM, respectively), but infliximab-TNF complex elimination was slower in Crohn's disease than in rheumatoid arthritis (k(int) = 0.024 vs 0.061 day(-1), respectively). Terminal elimination half-lives were 13.5, 21.5 and 16.5 days for rheumatoid arthritis, Crohn's disease and ankylosing spondylitis, respectively. Estimated amounts of free target were close to baseline values before the next infusion suggesting that TNF-α inhibition may not be sustained over the entire dose interval. CONCLUSIONS: The present study is the first to quantify the influence of target antigen dynamics on infliximab pharmacokinetics. Target-mediated elimination of infliximab may be complex, involving a multi-scale turnover of TNF-α, especially in patients with Crohn's disease. Additional clinical studies are warranted to further evaluate and fine-tune dosing approaches to ensure sustained TNF-α inhibition.
35286798 Fatal multiorgan dysfunction following repeated iodinated radiocontrast injection in a pat 2022 Jun BACKGROUND: Methotrexate is an antimetabolite drug that blocks dihydrofolate reductase and impairs cellular DNA synthesis. Administration of intravenous iodinated radiocontrast agents can cause life-threatening toxicity in patients receiving methotrexate. CASE: A 60-year-old female patient with rheumatoid arthritis underwent a craniotomy and clipping of a distal anterior cerebral artery aneurysm. The patient had been on low-dose oral methotrexate for the previous 5 years, which was discontinued two days before surgery. The patient received the first intravenous contrast agent injection (iohexol) during diagnostic cerebral angiography one day prior to surgery (50 ml) and the second contrast dose on the first postoperative day (60 ml). The patient developed severe methotrexate toxicity, leading to fatal multiorgan failure and death following repeated contrast imaging with intravenous iohexol. CONCLUSIONS: Even though low-dose oral methotrexate has minor adverse effects, life-threatening toxicity can be precipitated in the presence of iodinated contrast agents.
35126146 Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphoc 2021 Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA). Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared. Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group. Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.
35207306 Frequency of Renal Function Parameter Abnormalities in Patients with Psoriatic Arthritis a 2022 Feb 16 OBJECTIVE: Patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) commonly develop renal dysfunction due to either systemic inflammation or drug-related nephrotoxicity. This study compared renal function parameters in patients with PsA versus those with RA and examined the impact of clinical remission or disease relapse on renal function. METHODS: This single-center retrospective study was conducted at the University Hospital of Messina, Italy. Adult patients (aged ≥18 years) with PsA or RA who attended the rheumatology clinic within the past 6 months were identified from electronic medical records. RESULTS: In total, 45 patients with PsA (n = 23) or RA (n = 22) were included. The mean (standard deviation) age was 55.6 (15.9) years, and 78% of participants were female. Patient age, renal function, and medical history were generally similar between the two disease groups, although significantly more RA patients were smokers, and more PsA patients had comorbid hypertension. The prevalence of estimated glomerular filtration rate [eGFR] ≤90 mL/min/1.73 m(2) at 1, 6, and 12 months of treatment ranged from 38.5% to 58.3% in the PsA group and from 45.5% to 54.5% in the RA group and did not significantly differ between disease groups. Clinical remission did not appear to affect renal function parameters in either disease group; however, relapse was associated with significantly higher serum creatinine levels in PsA patients at the same timepoint. CONCLUSION: In this study, patients with PsA and RA had a similar prevalence of renal function parameter abnormalities over 12 months of treatment. Disease relapse may impact renal function in patients with PsA.
35275765 Biomarkers for the diagnosis and treatment of rheumatoid arthritis - a systematic review. 2022 Mar 16 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. AIM: To systematically explore the role of the biomarkers: C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η protein, and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. METHODS: A systematic review of the English literature using four different databases was carried out. RESULTS: CRP >7.1 mg/L predicted poor conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL, and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η protein with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity but was associated with increased radiographic damage (r = 0.46, p = 0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. The 14-3-3η protein significantly correlated with inflammation, bone rremodeling, and osteoporosis in RA patients (p < 0.05). In addition, the 14-3-3η protein positively correlated with RA duration (p = 0.003), disease aactivity, and positive RF (p = 0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity after 6 and 12 weeks of treatment (p < 0.05). The MBDA score was able to differentiate between small differences in disease activity, predicted remission over 1-year pperiod, and was a strong predictor of radiographic progression of RA. CONCLUSION: The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment, and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area.
35653787 Plumbagin relieves rheumatoid arthritis through nuclear factor kappa-B (NF-κB) pathway. 2022 May This study aimed to explore the effects of plumbagin on rheumatoid arthritis (RA) and its mechanism. The RA cell model was simulated following the treatment of interleukin-1β (IL-1β). After the treatment of various concentrations of plumbagin, the impact of plumbagin on the cell viability was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The collagen-induced arthritis (CIA) model was established using the solution of bovine type II collagen. Hematoxylin-eosin staining was used to observe the changes of ankle joint tissue, while enzyme-linked immunosorbent assay and western blot were applied to detect the level of inflammatory cytokines. Plumbagin inhibited the viability of human fibroblast-like synoviocytes (HFLS) at the concentration of 1 ~ 3.5 μM. The inhibitory effect of 1 μM plumbagin on cell proliferation was similar to that of methotrexate, the drug used as the positive control. Plumbagin downregulated the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) in IL-1β-treated HFLS, and suppressed the activation of IκB and nuclear factor kappa-B (NF-κB) as well as the entry of p65 into the nucleus. It was also demonstrated in animal experiments that plumbagin inhibited the activation of NF-κB pathway, down-regulated the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and MMPs, and alleviated joint damage in CIA-modeled mice. Collectively speaking, plumbagin might down-regulate the levels of inflammatory cytokines and MMPs through inhibiting the activation of the NF-κB pathway, thereby attenuating RA-induced damage to cells and joints.Abbreviations: CIA: Collagen-induced arthritis; ELISA: Enzyme-linked immuno sorbent assay; HFLS: Human fibroblast-like synoviocytes; IL-6: Interleukin-6; IL-1β: Interleukin-1β; NF-κB: nuclear factor kappa-B; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MMPs: Matrix metalloproteinase; OD: Optical density; RA: Rheumatoid arthritis; SDS: Sodium dodecyl sulfate; SD: Standard deviation; TNF-α: Tumor necrosis factor-α; PVDF: Polyvinylidene fluoride.
35147481 In silico molecular docking study of Andrographis paniculata phytochemicals against TNF-α 2022 Feb 11 Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine which plays a crucial role in controlling inflammatory responses. The pathway of Rheumatoid arthritis (RA) leading to TNF-alpha is activated by macrophages and quite often by natural killer cells and lymphocytes. In the inflammatory phase, it is believed to be the main mediator and to be anchored with the progression of different diseases such as ankylosing spondylitis, Crohn's disease, and Rheumatoid arthritis (RA). The major goal of this study is to use in silico docking studies to investigate the anti-inflammatory potential of a bioactive molecule from the medicinal plant Andrographis paniculata. The three-dimensional structures of different phytochemicals of A. paniculata were obtained from PubChem database, and the receptor protein was derived from PDB database. Docking analysis was executed using AutoDock vina, and the binding energies were compared. Bisandrographolide A and Andrographidine C revealed the highest score of -8.6 Kcal/mol, followed by, Neoandrographolide (-8.5 Kcal/mol). ADME and toxicity parameters were evaluated for these high scoring ligands and results showed that Andrographidine C could be a potent drug, whereas Neoandrographolide and Bisandrographolide A can be modified in in vitro and can lead to a promising drug. Further, the top scorer (Andrographidine C) and control drug (Leflunomide) were subjected to 100 ns MD Simulation. The protein complex with Andrographidine C had more stable confirmation with lower RMSD (0.28 nm) and higher binding energy (-133.927 +/- 13.866 kJ/mol). In conclusion, Andrographidine C may be a potent surrogate to the disease-modifying anti-rheumatic drugs (DMARD's) & Non-steroidal anti-inflammatory drugs (NSAID's) that has fewer or minor adverse effects and can aid in RA management.
35096912 Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis. 2021 Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.
35054471 COVID-19-A Trigger Factor for Severe Immune-Mediated Thrombocytopenia in Active Rheumatoid 2022 Jan 6 Thrombocytopenia is defined as a platelet count below 150,000/mm(3) for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm(3) to 150,000/mm(3) should be classified as having genuine thrombocytopenia or borderline thrombocytopenia. Thrombocytopenia is considered mild when the platelet count is between 70,000 and 150,000/mm(3) and severe if the count is less than 20,000/mm(3). Thrombocytopenia in rheumatoid arthritis is a rare complication, with an incidence estimated between 3 and 10%. The main etiological aspects include drug-induced thrombocytopenia and immune thrombocytopenic purpura. The most common hematological abnormalities in SARS-CoV-2 infection are lymphopenia and thrombocytopenia. It has been observed that the severity of thrombocytopenia correlates with the severity of the infection, being a poor prognosis indicator and a risk factor for mortality. COVID-19 can stimulate the immune system to destroy platelets by increasing the production of autoantibodies and immune complexes. Autoimmunity induced by viral infections can be related to molecular mimicry, cryptic antigen expression and also spreading of the epitope. During the COVID-19 pandemic, it is of great importance to include the SARS-CoV-2 infection in differential diagnoses, due to the increased variability in forms of presentation of this pathology. In this review, our aim is to present one of the most recently discovered causes of thrombocytopenia, which is the SARS-CoV-2 infection and the therapeutic challenges it poses in association with an autoimmune disease such as rheumatoid arthritis.
35543863 Role of booster with BNT162b2 mRNA in SARS-CoV-2 vaccination in patients with rheumatoid a 2022 May 11 Only case reports and small clinical series report the effects of booster vaccination with BNT162b2 in patients with rheumatoid arthritis (RA). We studied 200 patients with RA in clinical remission evaluated with the DAS28. All patients were vaccinated for SARS CoV-2 with the BNT162b2 mRNA vaccine. The value of anti-SARS-CoV 2 Spike RBD IgG antibodies was determined at T1 (3 weeks after first vaccination) and T2 (3 weeks after booster). In addition, patients underwent assessment of lymphocyte subpopulations by flow cytometry analysis before starting the vaccination cycle (T0). Furthermore, the serum antibody levels of 96 health care workers (HCWs) were analyzed for comparison. DAS28 values at T0, T1, and T2 indicated remission or low disease activity in all patients. Levels of anti-SARS CoV-2 IgG at T1 were higher in HCWs than in patients' groups: 1562.00 BAU WHO/mL [975.00-1632.00] vs 416.00 BAU WHO/mL [110.00, 1581.00], p <0.001. Anti-SARS COV2 IgG levels at T1 and at T2 were slightly lower in patients taking b/tsDMARDs than in patients under csDMARDs. Regression analysis evidenced age, treatment with abatacept (ABA), JAK inhibitors, and rituximab (RTX) as negative predictors of higher anti-SARS CoV-2 IgG levels at T1. Moreover, treatment with anti-IL6, anti-JAK, and anti-tumor necrosis factor (TNF) emerged as positive predictors of higher levels of anti-SARS CoV-2 IgG at T2. Our data show that despite the booster vaccine with BNT162b2, seroconversion in patients with rheumatoid arthritis is influenced by the background therapy, particularly for patients being treated with ABA and RTX.
35474094 Clinical characteristics and treatment of elderly onset adult-onset Still's disease. 2022 Apr 26 Adult-onset Still's disease (AOSD)-a systemic inflammatory disease-often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008-December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.
34879027 Updates in childhood Sjogren's syndrome. 2022 Apr 1 PURPOSE OF REVIEW: Childhood Sjogren's syndrome (cSS) is a rare, chronic autoimmune disease characterized by inflammation of the exocrine glands. cSS is underrecognized because of differences in clinical presentation compared with adults. Until recently, publications describing clinical manifestations in cSS were limited to case reports and case series with small numbers of patients. Diagnostic studies to assess glandular symptoms in adults, are less commonly obtained in children. RECENT FINDINGS: Recent cohort studies describe presenting diagnostic clinical features in large populations of cSS and demonstrate how current classification criteria, used in adults, are not applicable to children. Recurrent parotitis is the consistent predominant manifestation that is inversely correlated with age. Novel salivary biomarkers and salivary gland ultrasonography are important objective measure, which may improve diagnosis and disease monitoring. Standardized treatment recommendations are needed. SUMMARY: Findings from large cohort studies provide a framework for the future development of diagnostic criteria for cSS. Such criteria should incorporate objective measures that are easily obtained in children. Future research to improve understanding of the application of novel biomarkers and imaging and developing consensus on treatment recommendations is needed.
35589331 Sjögren's and non-Sjögren's sicca share a similar symptom burden but with a distinct sym 2022 May OBJECTIVES: Given the similarity in symptoms between primary Sjogren's syndrome (SjS) and non-SjS sicca syndrome (sicca), we sought to characterise clinical and proteomic predictors of symptoms in both groups in order to better understand disease mechanisms and help guide development of immunomodulatory treatments. These have not, to date, unequivocally improved symptoms in SjS clinical trials. METHODS: Serum proteomics was performed using O-link inflammation and cardiovascular II panels. SjS (n=53) fulfilled 2016 ACR/European Alliance of Associations for Rheumatology (EULAR) criteria whereas sicca (n=60) were anti-Ro negative, displayed objective or subjective dryness, and either had a negative salivary gland biopsy or, in the absence of a biopsy, it was considered that a biopsy result would not change classification status. Linear regression analysis was performed to identify the key predictors of symptoms. Cluster analysis was completed using protein expression values. RESULTS: EULAR-Sjögren's-Syndrome-Patient-Reported-Index (ESSPRI), EuroQoL-5 Dimension utility values, and anxiety and depression did not differ between SjS and sicca. Correlations between body mass index (BMI) and ESSPRI were found in sicca and to a lesser extent in SjS. Twenty proteins positively associated with symptoms in sicca but none in SjS. We identified two proteomically defined subgroups in sicca and two in SjS that differed in symptom burden. Within hierarchical clustering of the SjS and sicca pool, the highest symptom burden groups were the least distinct. Levels of adrenomedullin (ADM), soluble CD40 (CD40) and spondin 2 (SPON2) together explained 51% of symptom variability in sicca. ADM was strongly correlated with ESSPRI (spearman's r=0.62; p<0.0001), even in a multivariate model corrected for BMI, age, objective dryness, depression and anxiety scores. CONCLUSIONS: Obesity-related metabolic factors may regulate symptoms in sicca. Further work should explore non-inflammatory drivers of high symptom burden in SjS to improve clinical trial outcomes.
35208515 Corticosteroid-Induced Liver Injury in Adult-Onset Still's Disease. 2022 Jan 27 Background and Objectives: Adult-onset Still's disease (AOSD) is a rheumatic disease characterized by systemic inflammatory symptoms, including intermittent spiking fever, polyarthritis and a distinctive salmon-colored rash. Corticosteroids are the first-line treatment for AOSD. However, corticosteroids are potentially hepatotoxic in certain cases and may complicate the course of the disease. Materials and Methods: A 29-year-old female suffering from fever of unknown origin for two weeks was diagnosed with AOSD according to Yamaguchi's criteria. She received corticosteroids as the first-line treatment for AOSD and developed acute severe hepatitis. A diagnostic protocol has been performed. Results: Corticosteroid-induced liver injury was confirmed by clinical observation and rechallenge of the drug in this case. The result of liver biopsy also supported the diagnosis. Mycophenolic acid, a disease-modifying antirheumatic drug (DMARD) was chosen as an alternative treatment. AOSD remission was achieved under this treatment after three months. Conclusions: Severe acute hepatitis induced by corticosteroids, although very rare, may be observed in patients with AOSD. Drug-induced liver injury needs to be kept in mind when unexpected acute hepatitis is found. Mycophenolic acid could be a proper substitute medication in these cases.
33719871 Macrophage activation syndrome in patients with adult-onset Still's disease under tocilizu 2022 Jan 5 OBJECTIVES: Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. METHODS: The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. RESULTS: Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. CONCLUSION: MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.