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ID PMID Title PublicationDate abstract
27493790 Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or establish 2016 INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. METHODS: MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. RESULTS: Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. CONCLUSIONS: Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. TRIAL REGISTRATION NUMBER: NCT01039688; Results.
25848463 Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologi 2015 Mar 27 Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainly focused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.
27407260 Coexistence of rheumatoid arthritis and ankylosing spondylitis. 2015 Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic progressive inflammatory diseases, leading to joint damage and reducing the physical fitness of patients. They are among the most common rheumatic diseases. However, their etiology and symptomatology are different. Formerly, AS was often wrongly diagnosed as RA. Today there are no major diagnostic difficulties in differentiation between these diseases, thanks to modern laboratory tests and imaging. However, a problem may arise when the patient has symptoms typical for both diseases simultaneously. Cases of coexistence of RA with AS - according to our best knowledge - are rare. This study aims to compare our experience in diagnosis and treatment of concomitant RA and AS with the experience of other researchers. Implementation of the proper diagnostic algorithm, allowing for correct diagnosis of both diseases in one patient, may be useful for differential diagnosis of similar cases in the future.
26635790 The Interplay Between Monocytes/Macrophages and CD4(+) T Cell Subsets in Rheumatoid Arthri 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor necrosis factor α (TNFα), interferon γ (IFNγ), interleukin (IL)-1β, IL-6, and IL-17, eventually resulting in damage to the cartilage and underlying bone. The RA joint harbors a wide range of immune cell types, including monocytes, macrophages, and CD4(+) T cells (both proinflammatory and regulatory). The interplay between CD14(+) myeloid cells and CD4(+) T cells can significantly influence CD4(+) T cell function, and conversely, effector vs. regulatory CD4(+) T cell subsets can exert profound effects on monocyte/macrophage function. In this review, we will discuss how the interplay between CD4(+) T cells and monocytes/macrophages may contribute to the immunopathology of RA.
29942838 Comminuted distal humeral fracture treated using the Ilizarov technique in a patient with 2016 Apr The goal of treatment for distal humeral fractures in patients with rheumatoid arthritis (RA) is to obtain sufficient bone union and good elbow function. However, treating comminuted distal humeral fractures in patients with RA and osteoporosis is challenging. We present the case of a 58-year-old woman with RA and osteoporosis who suffered a comminuted distal humeral fracture and was successfully treated with the Ilizarov technique. The Ilizarov technique is minimally invasive compared with conventional open surgery, can obtain good stabilization, and allows earlier rehabilitation, even if the fractured bone is severely osteoporotic. The patient exhibited good elbow function and alignment at the final follow-up examination (18 postoperative months). To the best of our knowledge, the present case is the first in which a comminuted distal humeral fracture in a patient with RA and severe osteoporosis was successfully treated with an Ilizarov external fixator.
26284069 T Cell Migration in Rheumatoid Arthritis. 2015 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies.
25664229 Association of ANCA associated vasculitis and rheumatoid arthritis: a lesser recognized ov 2015 BACKGROUND: ANCA associated vasculitis (AAV) is an autoimmune disease with significant morbidity and mortality, in which diagnostic delay is associated with worse outcomes. AAV is rarely found in association with other immune mediated diseases. Early recognition of such overlaps enables more timely diagnosis and may impact on disease outcome. We reviewed cases of AAV in which there was an overlap with rheumatoid arthritis (RA). METHODS: We performed a retrospective analysis of our vasculitis database for patients who had a diagnosis of AAV and RA, and a literature search to find other reported cases of this overlap syndrome. RESULTS: We found six subjects who had a diagnosis of RA and developed AAV at a median of 10.5 years (range 4-43 years) after the diagnosis of RA. They had been treated with a mean of 2 disease modifying drugs (0-4) and all had evidence of renal involvement with median creatinine of 227 μmol/l (range 128-700 μmol/l). Only one had a diagnosis of granulomatosis with polyangiitis, while the rest had a clinical diagnosis of microscopic polyangiitis. Half of the patients had positive rheumatoid factor (RhF) at the time of vasculitis diagnosis, three had MPO-ANCA, one PR3-ANCA, and two had ANCA-negative pauci-immune vasculitis. Additionally, we found 29 other cases reported of this overlap, which also most frequently presented with vasculitic renal manifestations, and were frequently RhF positive at the time of AAV diagnosis. CONCLUSIONS: AAV occurs in subjects with RA rarely, and often with significant delay from the first rheumatological manifestations. Renal involvement is common.
26688750 Computerised versus conventional methodology of radiographic joint destruction assessment 2015 OBJECTIVES: To compare computerised and conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis (RA). METHODS: We investigated the contribution of the 3rd-to-5th carpometacarpal joints (CMC3-5, which are excluded in computerised assessment so far owing to bone overlapping) to total joint space narrowing (JSN) scores in two cohorts of patients with early RA (n=392). Next, we investigated agreement between JSN scoring using single time point individual joint-based method (individual joint of a single time point (IJSTP), reflecting computerised reading) and conventional JSN scoring using the Sharp-van der Heijde (SvdH) method in a cohort of patients with early RA (n=59). We used intraclass correlation coefficients (ICCs), Bland and Altman plots, and linear mixed modelling to analyse differences in progression between two methods. Radiographs were available at baseline, and at 1 and 2 years of follow-up. RESULTS: Of all joints affected by JSN at baseline or JSN progression during 2 years of follow-up, 3.9% and 6.6% concerned CMC3-5. Exclusion of CMC3-5 resulted in a decrease of 1.9-4.6% in JSN progression scores during 2 years of follow-up. The ICCs for JSN progression scores using IJSTP with or without CMC3-5 compared with SvdH were 0.71-0.81 and 0.69-0.78 at 1 and 2 years of follow-up. Signal-to-noise ratios for IJSTP-based and SvdH scoring were 0.51 and 0.58, respectively. The progression rate for each year was not statistically significantly different between two scoring methods (p=0.59 and 0.89). CONCLUSIONS: This study showed that excluding CMC3-5 has limited influence on JSN (progression) scores and showed the feasibility of using IJSTP-based reading for computerised scoring of JSN (progression) in RA.
26115972 [Kikuchi-Fujimoto's disease and adult-onset Still's disease. A rare co-occurence]. 2015 Dec Kikuchi-Fujimoto's disease and adult-onset Still's disease are rare inflammatory conditions with overlapping clinical features. Adult-onset Still's disease causes high fevers, a typical salmon-colored rash, and joint pain. The principal symptom of Kikuchi's disease is cervical lymphadenopathy with typical histopathological features including extensive necrosis of the involved lymph nodes. Here, we report on a rare case of concurrent adult-onset Still's disease and Kikuchi-Fujimoto syndrome in a young Caucasian patient.
27833370 Management of Amavata (rheumatoid arthritis) with diet and Virechanakarma. 2015 Oct Amavata is a disease in which vitiation of Vata Dosha and accumulation of Ama take place in joint(s), and it simulates rheumatoid arthritis (RA) at modern parlance. Shamana (conservative) and Shodhana (biological purification of the body) treatments are advised in Ayurveda whereas anti-inflammatory, analgesics, steroids, and disease-modifying antirheumatic drugs are required for its management as per modern medicine, which are not free from side effects. A female was suffering from multiple joints pain with swelling, severe morning stiffness, restricted movements, malaise, and Mandagni (poor appetite) for the past 1½ year, which was classified as Amavata/RA (having 7/10 score as per the RA classification criteria, 2010). After Deepana-Pachana and Snehapana, Virechanakarma was done by the administration of Trivrita Avaleha and castor oil. The assessment was made on the basis of relief in signs and symptoms and serological findings of RA factor, C-reactive protein (CRP), immunoglobulin E (IgE), and erythrocyte sedimentation rate. After Virechanakarma, RA factor reduced from 94.0 IU/ml to 50.0 IU/ml, CRP reduced from 22.7 mg/L to 1.8 mg/L, and IgE was reduced from 680 kU/L to 53.7 kU/L, with remarkable reduction in joints pain and swelling. Further, by avoiding specific Nidanas, i.e., known allergens for food, drugs, and inhalants, the patient has relief in almost all signs and symptoms for the past 1 year of follow-up with least medications. This single case report highlights that Amavata/RA can be managed with appropriate diet regimen, Virechanakarma and can be managed effectively with minimum requirement of medicines.
27721779 Anti-Cyclic Citrullinated Peptide Antibody-Positive Meningoencephalitis in the Preclinical 2016 May Rheumatoid meningoencephalitis (RM) is a rare complication of rheumatoid arthritis (RA). This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI) showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces. The patient was diagnosed with RM despite lack of signs suggesting RA. His symptoms drastically improved with intravenous infusion of high-dose methylprednisolone. Two months later, he developed RA. The findings in this patient suggest that RM could develop prior to the onset of RA. Anti-CCP antibody and MRI findings may be useful for the diagnosis of RM, regardless of RA history.
25613167 Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment optio 2015 Feb Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a heterogeneous entity, usually presenting with high fever, arthralgia, skin rash, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. The diagnosis is clinical and empirical, where patients are required to meet inclusion and exclusion criteria with negative immunoserological results. There are no clear-cut diagnostic radiological or laboratory signs. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required. Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control. The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD.
27903264 Adult-onset Still's disease: evaluation of prognostic tools and validation of the systemic 2016 Dec 1 BACKGROUND: Adult-onset Still's disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients. METHODS: This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed. RESULTS: One hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of ≥ 7.0 was reported. CONCLUSIONS: Our study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death.
27886796 Adult-onset Still's disease: Advances in the treatment. 2016 Apr Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder mainly characterized by persistent high spiking fevers, evanescent rash, and joint involvement. The pathogenesis of AOSD is only partially known, but pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-18, and IFN-γ seem to play a major role in this disorder. AOSD is at the crossroad of auto-inflammatory syndromes and autoimmune diseases. It is diagnosed by exclusion to determine the presence of high serum ferritin levels, which is usually >1000 μg/L. AOSD is generally treated with non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs). Although information on biologic therapy in the management of AOSD is scarce, these drugs represent a major breakthrough in the management of patients with AOSD refractory to corticosteroids or conventional DMARDs or in patients presenting life-threatening manifestations. In this regard, TNF-α, IL-1, and IL-6 antagonists had been proved effective in patients with AOSD.
26573883 Discriminant validity study of Achilles enthesis ultrasound. 2016 Jul OBJECTIVE: We want to know if the ultrasound examination of the Achilles tendon in spondyloarthritis is different compared to other rheumatic diseases. MATERIAL AND METHODS: We studied 97 patients divided into five groups: rheumatoid arthritis, spondyloarthritis, gout, chondrocalcinosis and osteoarthritis, exploring six elementary lesions in 194 Achilles entheses examined. RESULTS: In our study the total index ultrasonographic Achilles is higher in spondyloarthritis with significant differences. The worst elementary spondyloarthritis lesions for discriminations against other pathologies were calcification. CONCLUSIONS: This study aims to demonstrate the discriminant validity of Achilles enthesitis observed by ultrasound in spondyloarthritis compared with other rheumatic diseases that may also have ultrasound abnormalities such enthesis level.
28491854 MPO-ANCA-associated necrotizing glomerulonephritis in rheumatoid arthritis; a case report 2017 Mar BACKGROUND: Renal involvement in rheumatoid arthritis (RA) is common and has a negative impact on patient survival. Only few cases have been reported of necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA. CASE PRESENTATION: We report a patient with RA who developed a necrotizing GN associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a 27-year history of RA under secukinumab was referred to our nephrology clinic with worsening renal function associated with microhematuria and proteinuria. Our laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA (615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient was treated with 3 consecutive pulses of methylprednisolone followed by oral prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a 10-month follow-up, the arthritis remains well-controlled, renal function stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL). CONCLUSIONS: Necrotizing GN is a rare but a serious condition and an early diagnosis is essential to treatment. This is the first case of necrotizing GN (without extra-renal manifestations of vasculitis) in a patient with active RA, successfully treated with RTX.
27042404 Contributions of neutrophils to the adaptive immune response in autoimmune disease. 2015 Dec Neutrophils are granulocytic cytotoxic leukocytes of the innate immune system that activate during acute inflammation. Neutrophils can also persist beyond the acute phase of inflammation to impact the adaptive immune response during chronic inflammation. In the context of the autoimmune disease, neutrophils modulating T and B cell functions by producing cytokines and chemokines, forming neutrophil extracellular traps, and acting as or priming antigen presentation cells. Thus, neutrophils are actively involved in chronic inflammation and tissue damage in autoimmune disease. Using rheumatoid arthritis as an example, this review focuses on functions of neutrophils in adaptive immunity and the therapeutic potential of these cells in the treatment of autoimmune disease and chronic inflammation.
27822280 The Influence of Pain, Weakness and Rheumatoid Factor Status on Depression Incidence Among 2016 Sep BACKGROUND: Increased prevalence of depression among patients with Rheumatoid arthritis (RA) has been described previously. However, the impact of depression among Iranian patients has not yet been investigated. OBJECTIVES: Here, the prevalence of depression was assessed and the effect of disease-related characteristics including pain, weakness and rheumatoid factor (RF) status on incidence of depression was evaluated. MATERIALS AND METHODS: Patients with RA, who were referred to rheumatology clinics of Kermanshah University of Medical Sciences and healthy subjects from the general population of Kermanshah participated in this investigation. Depression was assessed using Beck's depression inventory II (BDI II). Pain and weakness were assessed subjectively by patients' self-report. Data was collected during a year between 2012 and 2013. Chi-square test and independent t-test were used. RESULTS: One hundred and seventy-one patients with RA and 198 healthy individuals participated in this investigation. In the RA group, depressive mood was detected in 45.7% of patients, which was significantly higher than healthy subjects (P = 0.008). Depression was more common in elderly patients (> 50 years old) in comparison with healthy subjects at a similar age (P = 0.03). Pain and weakness had no influence on depression incidence (P = 0.14 and 0.19, respectively) whereas patients with negative RF status were significantly more susceptible to severe depression (P: 0.001). CONCLUSIONS: Depression is more common among Iranian patients with RA (45%) than healthy subjects regardless of gender. Depression has a significant association with older age. Negative RF status may predict future risk of depression.
27659057 Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less 2016 Sep 23 BACKGROUND: In patients with rheumatoid arthritis (RA) clinical measures of disease activity may not reliably discriminate between patients with active inflammatory disease and those with concomitant fibromyalgia (FM). Recent work has shown RA patients with a 28 tender joint count (TJC) minus swollen joint count (SJC) of 7 or more (joint count criteria) are more likely to meet classification criteria for FM. This study aimed to determine whether RA patients meeting clinical criteria for FM had lower levels of joint inflammation as determined by ultrasound (US). METHODS: RA patients with DAS28 > 2.6 were recruited. Patients underwent clinical assessment including ultrasound examination of the hands and wrists with quantification of grey scale (GS) and power Doppler (PD) synovitis. Patients completed questionnaires to assess pain, fatigue, disability and psychological comorbidity. RESULTS: Patients meeting either of the FM criteria had higher scores for disease activity, depression, disability and fatigue. Those meeting both the joint count and classification FM criteria had significantly lower levels of GS and PD inflammation on US. CONCLUSIONS: RA patients with concomitant FM, as determined by widespread soft tissue tenderness but fewer clinically inflamed joints, have higher disease activity scores but may have lower levels of synovial inflammation on US. This has implications for the identification and management of these patients who may not respond to conventional therapy and hence be more suitable for alternative approaches to treatment.
26448803 Radiocarpal and Midcarpal Instability in Rheumatoid Patients: A Systematic Review. 2015 BACKGROUND: This study was aimed at identifying the criteria for the diagnosis of Radiocarpal instability in rheumatoid arthritis RA). METHODS: The main databases were searched to identify studies describing the pathophysiology of Radiocarpal instability in patients with RA. We focussed on the epidemiology, radiographic parameters, criteria for instability and on treatment options. Results. In the search 108 articles were found, of these 12 studies were included for this review. Instability occurs in at an average of 35.2% of the rheumatoid wrists. The instability was found between 8 and 13 years after onset of rheumatoid arthritis. A strong correlation was found between instability, duration of RA and Larsen score. Several radiographic methods were described to evaluate Radiocarpal instability in RA. Several treatment options for instability in patients with RA are described. All with their own indications and limitations. CONCLUSION: On a standard AP radiograph deformity can be measured using the carpal height and the ulnar translation index of Chamay. This gives an indication for instability. For describing the deterioration of the joints the Larsen score is most used. If there are more radiographs in time the Simmen classification can be used. For real assessment of instability dynamic radiographs are needed. LEVEL OF EVIDENCE: Level IV.