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ID PMID Title PublicationDate abstract
35567732 The value of ultrasound and magnetic resonance imaging scoring systems in explaining handg 2022 Jun PURPOSE: The goal of this study is to investigate the relationship between joint inflammation and damage of the wrists and hands, measured by semiquantitative ultrasound and magnetic resonance imaging scoring systems, with functional disability and handgrip strength (HGs). MATERIALS AND METHODS: Consecutive adult RA patients with active disease, as defined by a Disease Activity Score 28 joints C-reactive protein (DAS28-CRP) > 3.2, underwent a cross-sectional evaluation comprehensive of a clinimetric assessment, an HGs evaluation, an ultrasound assessment aimed at calculating the UltraSound-CLinical ARthritis Activity (US-CLARA), and a magnetic resonance imaging scored according to the modified Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score (mod SAMIS). The Spearman's rho correlation coefficient was used to test the correlations. RESULTS: Sixty-six patients with RA were investigated (age 55.6 ± 12.2 years). The mod SAMIS total score and the US-CLARA had a weak but significant correlation (rho = 0.377, p = 0.0018). Among the mod SAMIS sub-scores, there was a significant relationship between mod SAMIS bone edema (SAMIS-BME) and US-CLARA (rho = 0.799, p < 0.001) and mod SAMIS synovitis (SAMIS synovitis) and US-CLARA (rho = 0.539, p < 0.001). There were also significant negative relationships between the HGs score and the mod SAMIS total score and US-CLARA (rho = - 0.309, p = 0.011 and rho = - 0.775, p < 0.0001, respectively). CONCLUSIONS: BME and synovitis have an influence on the function of the upper extremities. The US-CLARA and the mod SAMIS total score are intriguing options for semiquantitative assessment of joint inflammation and damage in RA.
34633502 [Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with me 2022 Apr Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF‑α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.
35089382 [What are the indications for a synovectomy?]. 2022 Apr In accordance with the rheumatological concept of "hit hard and early", the timing of synovectomy should also be selected to be as early as possible and should be adjusted to the onset of the effect of biologicals in order to prevent joint destruction. This means that after an early diagnosis of rheumatoid arthritis and start of drug therapy, a low disease activity has been achieved and a rebellious joint is evident, a very prompt synovectomy is indicated.
35039354 Disseminated cutaneous Mycobacterium haemophilum infection in a patient on infliximab for 2022 Jan 17 Mycobacterium haemophilum is a rarely encountered pathogen that is difficult to identify given its unique growth requirements. It is most often seen in adult patients who are immunosuppressed due to advanced HIV or haematological malignancy. Our case highlights a typical presentation of an atypical pathogen in a patient with rheumatoid arthritis receiving anti-tumour necrosis factor therapy. This case represents an important patient population in whom this previously rare infection is increasingly common.
35062897 Epstein-Barr viral corneal stromal keratitis occurring during rheumatoid arthritis treatme 2022 Jan 21 BACKGROUND: A case of Epstein-Barr viral (EBV) corneal stromal keratitis during rheumatoid arthritis (RA) treatment is presented. CASE PRESENTATION: A 74-year-old female undergoing RA treatment was previously treated for bacterial corneal ulcer and herpetic keratitis and healed with antibiotic eye drops and topical anti-herpes ointment. At the first visit to our hospital, she presented with findings of monocular posterior interstitial keratitis with neovascularization mostly located in the inferior cornea with a corneal epithelial defect. The right eye showed no thinning of the corneal periphery and anterior uveitis. Her RA had subsided with oral steroid treatment, and infectious mononucleosis (IM) had not developed. EBV DNA could be detected in her corneal sample. After an extended but ineffective period to antibiotic treatment the corneal infiltrate responded rapidly to topical corticosteroids. CONCLUSION: EBV can cause stromal keratitis without IM during treatment for RA.
34940891 [Latest findings from the RABBIT register]. 2022 Mar Since 2001 rheumatologists throughout Germany have been recruiting patients with rheumatoid arthritis into the biologics register (rheumatoid arthritis: observation of biologics treatment, RABBIT) to investigate the long-term safety and efficacy of modern antirheumatic treatment. Over the past 20 years more than 20,000 patients have been enrolled in the prospective cohort study. This article summarizes the research findings published in 2020/2021, focusing on safety aspects, factors influencing treatment efficacy and patient-reported outcomes. With herpes zoster, facial nerve palsy and psoriasis, several adverse events were investigated that were either reported as a safety signal from clinical trials or through the EudraVigilance database or occurred as a paradoxical reaction under drug treatment. For these events, the influence of biological disease-modifying antirheumatic drug (DMARD) treatment was analyzed. In the publication on herpes zoster, we also considered drug treatment with Janus kinase inhibitors. Severe overweight can influence the success of treatment. There are gender-specific differences and the mode of action of a treatment also determines whether obesity reduces the response to treatment. The majority of patients observed in RABBIT were satisfied with the treatment they have received after 1 year. We were able to show which factors either favor or negatively influence satisfaction with the effectiveness and safety of the treatment. This review article shows that long-term observational studies such as the RABBIT register contribute to the understanding of treatment risks and can identify factors that influence the effects of treatment even after two decades of data collection.
35583063 [Increased expression of inhibitor of differentiation 2 (Id2) in CD4(+)T cells in joint sy 2022 Apr Objective To investigate the effect of inhibitor of differentiation 2 (Id2) on the proportion of CD4(+)T cells by detecting the proportion of CD4(+)T cell subsets and Id2 expression in peripheral blood and joint synovial fluid of patients with rheumatoid arthritis (RA). Methods A total of 51 RA patients (including 18 patients providing synovial fluid) and 31 healthy controls (HCs) were enrolled. The proportions of CD4(+)T cells, Th1 cells, and Th17 cells, and their expression of Id2 in peripheral blood and synovial fluid of RA patients and HCs were detected by flow cytometry. Results Compared with HCs group, the proportions of circulating CD4(+)T cells, Th1 cells, and Th17 cells and their expression of Id2 in RA patients did not change significantly. The proportions of CD4(+)T cells and Th1 cells, and Id2 expression in CD4(+)T cells in synovial fluid of RA patients were significantly higher than those in peripheral blood of RA patients and HCs. The expression rate of Id2 in CD4(+)T cells was positively correlated with the expression of IFN-γ, but not with erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Disease Activity Score 28 (DAS28). Conclusion CD4(+)T cells are enriched in RA synovial fluid, and their Id2 expression may promote Th1 cell differentiation.
34477209 A case of eosinophilic granulomatosis with polyangiitis after prolonged intervals of an an 2022 Jan 7 An 83-year-old woman with a history of asthma complained of left abdominal pain and was admitted to our hospital. She was treated with tocilizumab, an anti-interleukin (IL)-6 receptor antibody, with a prolonged interval for rheumatoid arthritis (RA). Laboratory tests revealed a remarkable increase in eosinophil count and inflammatory markers with negative antineutrophil cytoplasmic antibodies. Echocardiography revealed pericardial fluid retention, and contrast-enhanced computed tomography revealed the thickening of the gastric antrum wall. Upper gastrointestinal endoscopy and biopsy revealed eosinophilic infiltration into the gastric mucosal epithelium. She was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) with pericarditis and eosinophilic gastroenteritis. High-dose glucocorticoids with intermittent intravenous cyclophosphamide (IVCY) were initiated, resulting in remission. As IL-6 is involved in the pathogenesis of allergic diseases such as asthma, our case can provide insights into the pathogenic role of IL-6 in EGPA as the development of EGPA in our case may have been triggered by IL-6 signals enhanced with tocilizumab interval prolongation.
35572409 Far infrared irradiation suppresses experimental arthritis in rats by down-regulation of g 2022 May INTRODUCTION: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear. OBJECTIVES: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA. METHODS: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting. RESULTS: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPβ, c-Fos, GR, HNF-3β, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment. CONCLUSION: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA.
35197363 Waiting for JAK inhibitor safety data. 2022 Feb The US Food and Drug Administration (FDA) has recently added a new 'black box warning' on all currently approved Janus kinase (JAK) inhibitors indicated for the treatment of arthritis and other inflammatory conditions based on results from the ORAL Surveillance study of tofacitinib versus tumour necrosis factor alpha inhibitors in rheumatoid arthritis. This is a warning difficult to ignore because the data, being from a randomised controlled trial, are of high fidelity and hard to reproach. It is especially problematic because safety data for all the other JAK inhibitors will be pending for several years. So how might we proceed, without being bound by our stasis? The lack of absolute certainty seems to require a pragmatic approach to the routine care use of JAK inhibitors. The patients who were at greatest risk were older and had other risk factors for the corresponding adverse events, in keeping with effect modification. This highlights the need to focus on risk stratification when tailoring therapy. In this viewpoint, we propose a simple illustration to guide clinical decision-making. First, identify general risk factors for venous thromboembolic event (VTE), major adverse cardiac event (MACE) and cancer (age>65 years and smoking) and whether there is a previous history of VTE, MACE or cancer. Then, evaluate risk based on the number of other risk factors for VTE and the number of other risk factors for MACE. Ultimately, 'treat-to-target' will in the end always be 'treat-to-agreement'. As we have done in the past, and will do in the future, the optimal treatment strategy will have to be tailored based on individual patient risk factors and preferences in a shared-decision process.
35081065 Midfoot Derotational Osteotomy for Ankylosing Inversion Deformity in Patients with Rheumat 2022 Jan 26 CASE: Ankylosing midfoot inversion deformities in 3 patients with rheumatoid arthritis (RA) treated by midfoot derotational osteotomy to remove the pain due to excessive loading of the fifth metatarsal base and to obtain the plantigrade position are presented. All cases achieved sufficient correction and good clinical and radiographic improvement. CONCLUSION: Midfoot derotational osteotomy seems useful and has the possibility to be a definitive surgical procedure for ankylosing inversion deformity in patients with RA. Osteotomy should be performed from both medial and lateral sides, and careful retraction of soft tissues should always be kept in mind.
34734772 Silicone Implant Arthroplasty for Severe Bony Ankylosis of the Proximal Interphalangeal Jo 2022 Jan Arthrodesis and prosthetic arthroplasty have been used to treat severe proximal interphalangeal (PIP) joint arthritis. Silicone implant arthroplasty is an established treatment for rheumatoid arthritis (RA) of the fingers. However, few studies have reported the application of silicone implant arthroplasty for the treatment of severe ankylosis of the PIP joint in RA patients. The authors report, for the first time, the case of a 46-year-old woman who presented with severe bony ankylosis of the right fourth and fifth PIP joints at greater than 90° of flexion. Proximal interphalangeal silicone arthroplasty in combination with reconstruction of the extensor mechanism was successfully performed in the affected joints. Four years after surgery, active flexion of the fourth and fifth PIP joints was 55° and 75°, respectively, with an extensor lag of only 5° without pain and joint instability. Proper repair of the extensor mechanism with shortening of the central slips and mobilization of the lateral bands dorsally was most important in maintaining the extended position of the PIP joints. Proximal interphalangeal silicone arthroplasty with intensive reconstruction of the extensor mechanism could become a potential treatment option to maintain joint mobility even in severe ankylosis of the PIP joints in RA patients. [Orthopedics. 2022;45(1):e53-e56.].
35029180 Early treatment of rituximab combined with eltrombopag for secondary thrombocytopenic purp 2022 Jan 14 RATIONALE: Secondary immune thrombocytopenic purpura (ITP) is also known as acquired thrombocytopenic purpura, autoimmune disease is usually one of the important causes. There are few reports about treatment of refractory thrombocytopenic purpura in rheumatoid arthritis (RA). We report a case of refractory ITP in which changes in platelet-related markers with therapeutic agents are worthy of the attention of clinicians. PATIENT CONCERNS: A 69-year-old woman admitted for ecchymosis on the neck and arms for 15 days presented to our hospital. She was diagnosed with RA 5 years ago. DIAGNOSIS: The diagnosis met the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria. The disease activity score 28 (DAS-28) was 4.6, indicating that the disease activity was moderate. INTERVENTIONS: Treatment with first-line therapies and second-line treatment--eltrombopag (EPAG) were ineffective. Therefore, we performed rituximab combined with a low dose of EPAG. OUTCOMES: The patient received 2 cycles of rituximab combined with EPAG, and reported no new petechiae on her buccal mucosa and limbs during follow-up. LESSONS: This case suggests that early treatment of rituximab combined with EPAG is beneficial to patients with refractory ITP in RA. In terms of disease dynamic monitoring, immature platelet fraction (IPF) may be an auxiliary indicator for predicting efficacy, but its significance needs further study.
34248117 Immune Reconstitution Inflammatory Syndrome Associated with Pneumocystis jirovecii Pneumon 2022 Jan 15 A 68-year-old woman presenting with rheumatoid arthritis was admitted due to pancytopenia caused by methotrexate. Pneumocystis jirovecii pneumonia was diagnosed based on the abnormal shadows observed on chest computed tomography, the presence of serum β-D-glucan, and positive P. jirovecii-DNA results in a sputum analysis. Subsequently, after treatment with leucovorin and trimethoprim-sulfamethoxazole, lung consolidation was found to be aggravated, along with a rapidly increasing leukocyte count. In addition, cytomegalovirus colitis was diagnosed. Both conditions were associated with immune reconstitution inflammatory syndrome caused by recovery from leukopenia. The patient was successfully treated with intravenous methylprednisolone pulse therapy and ganciclovir.
35324478 The synovial and blood monocyte DNA methylomes mirror prognosis, evolution, and treatment 2022 May 9 Identifying predictive biomarkers at early stages of inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes (MOs) and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) MOs in a prospective cohort of patients with early inflammatory arthritis. DNA methylation profiles of undifferentiated arthritis (UA) blood MOs exhibited marked alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF MOs after comparing patients with UA grouped by their future outcomes, i.e., good versus poor. Patient profiles in subsequent visits revealed a reversion toward a healthy level in both groups, those requiring disease-modifying antirheumatic drugs and those who remitted spontaneously. Changes in disease activity between visits also affected DNA methylation, which was partially concomitant in the SF of UA and in blood MOs of patients with rheumatoid arthritis. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity, and treatment efficacy for the personalized clinical management of early inflammatory arthritis.
34637523 Long-term good outcome of the fibrocavitary form of pulmonary Mycobacterium avium complex 2022 Jan 7 A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.
35234444 Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatm 2022 Mar 18 Selective targeting of TNF in inflammatory diseases such as rheumatoid arthritis (RA) has provided great therapeutic benefit to many patients with chronic RA. Although these therapies show initially high response rates, their therapeutic benefit is limited over the lifetime of the patient due to the development of antidrug antibodies that preclude proper therapeutic benefits. As a result, patients often return to more problematic therapies such as methotrexate or hydroxychloroquine, which carry long-term side effects. Thus, there is an unmet medical need to develop alternative treatments enabling patients to regain the benefits of selectively targeting TNF functions in vivo. The protein kinase TAK1 is a critical signaling node in TNF-mediated intracellular signaling, regulating downstream NF-κβ activation, leading to the transcription of inflammatory cytokines. TAK1 inhibitors have been developed but have been limited in their clinical advancement due to the lack of selectivity within the human kinome and, most importantly, lack of oral bioavailability. Using a directed medicinal chemistry approach, driven by the cocrystal structure of the TAK1 inhibitor takinib, we developed HS-276, a potent (K(i) = 2.5 nM) and highly selective orally bioavailable TAK1 inhibitor. Following oral administration in normal mice, HS-276 is well tolerated (MTD >100 mg/Kg), displaying >95% bioavailability with μM plasma levels. The in vitro and in vivo efficacy of HS-276 showed significant inhibition of TNF-mediated cytokine profiles, correlating with significant attenuation of arthritic-like symptoms in the CIA mouse model of inflammatory RA. Our studies reinforce the hypothesis that TAK1 can be safely targeted pharmacologically to provide an effective alternative to frontline biologic-based RA therapeutics.
34991984 Pre-RA: Can early diagnosis lead to prevention? 2022 Mar Rheumatoid arthritis (RA) is currently diagnosed and treated once an individual displays the clinical findings of inflammatory arthritis (IA). However, growing evidence supports that there is a 'pre-RA' stage that can be identified through factors such as autoantibodies in absence of clinically apparent IA. In particular, biomarkers, including antibodies to citrullinated protein antigens (ACPA), demonstrate a high risk for future IA/RA, and multiple clinical trials have been developed to intervene in individuals in pre-RA to prevent or delay clinically apparent disease. Herein, we will discuss in more depth what is currently known about the natural history of RA, and the emerging possibility that early 'diagnosis' of RA-related autoimmunity followed by an intervention can lead to the delay or prevention of the first onset of clinically apparent RA.
35611484 [CME Rheumatology 26: Rheumatological Cases]. 2022 CME Rheumatology 26: Rheumatological Cases Abstract. Special rheumatological cases are illustrated using various examples. On the one hand we present differential diagnoses and causes of a "Baker's cyst", on the other hand a case of involvement of the cervical spine in rheumatoid arthritis. Usually, the medical history and precise clinical examination will lead us in the right diagnostic direction. Further clarifications such as laboratory analyses or imaging procedures are used in a targeted manner, taking into account the clinic.
35039359 Hereditary haemochromatosis presenting to rheumatology clinic as inflammatory arthritis. 2022 Jan 17 Hereditary haemochromatosis (HH) is the most commonly identified genetic disorder in Caucasians. HH has a wide variety of clinical manifestations. As such, the presenting complaint in new diagnoses of HH can be non-specific such as fatigue; however, joint symptoms such as arthralgia are also common. These joint symptoms closely mimic the features of other musculoskeletal diseases such as rheumatoid arthritis (RA). Early diagnosis of HH is key to prevent long-term irreversible complications such as liver damage, diabetes and degenerative joint disease. We present a case of HH which was initially suspected to be early RA, with ultrasound findings of active synovitis. High clinical suspicion, a raised serum ferritin followed by genetic testing for C282Y mutation confirmed the diagnosis of HH. The synovitis responded to corticosteroids and was suspected to be due to pseudogout a known complication of HH. Early diagnosis and treatment resulted in a favourable outcome.