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ID PMID Title PublicationDate abstract
27936399 Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheum 2017 Jan Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.
27179599 Rheumatoid arthritis and pulmonary nodules: An unexpected final diagnosis. 2017 May We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy.
28273637 FGF21 exerts comparable pharmacological efficacy with Adalimumab in ameliorating collagen- 2017 May Previous studies have reported that Fibroblast growth factor 21 (FGF21) can regulate inflammation and may play an important role in inflammatory and immune-mediated diseases, such as autoimmune diseases. Adalimumab is one of the clinically effective anti-rheumatoid arthritis (RA) drugs. The aim of this study was to compare the therapeutic efficacy of FGF21 and Adalimumab on collagen-induced arthritis (CIA) model mice. Mice with CIA were subcutaneously treated with FGF21 or Adalimumab at dose of 1mgkg(-1)d(-1), respectively. Our results showed that FGF21 significantly alleviated the severity of arthritis by reducing cellular immune responses and exerted the similar anti-inflammatory effects with Adalimumab in decreasing the mRNA and protein expression levels of IL-2, IL-6 and IL-17. However, the expression levels of IL-1β, RANKL and IL-10 in the mice treated with FGF21 were decreased 2.2-fold, 2.5-fold and increased 4.3-fold compared with Adalimumab, respectively. However, the levels of TNF-α in the mice treated with Adalimumab were lower than those in the mice treated with FGF21. Western blotting results demonstrated that FGF21 displayed equivalent effects with Adalimumab by inhibiting NF-κB/IκBα signaling pathway. However, FGF21 could also regulate systematic inflammatory response and the mechanism maybe related to other signal pathway. In summary, FGF21 exerts comparable pharmacological efficacy with Adalimumab by regulating systematic inflammatory response, providing that FGF21 may be a promising therapeutic agent for RA patients.
28441721 Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchyma 2017 Apr 22 Extracellular vesicles (EVs) are important mediators of cell-to-cell communication pathways via the transport of proteins, mRNA, miRNA and lipids. There are three main types of EVs, exosomes, microparticles and apoptotic bodies, which are classified according to their size and biogenesis. EVs are secreted by all cell types and their function reproduces that of the parental cell. They are involved in many biological processes that regulate tissue homeostasis and physiopathology of diseases. In rheumatic diseases, namely osteoarthritis (OA) and rheumatoid arthritis (RA), EVs have been isolated from synovial fluid and shown to play pathogenic roles contributing to progression of both diseases. By contrast, EVs may have therapeutic effect via the delivery of molecules that may stop disease evolution. In particular, EVs derived from mesenchymal stem cells (MSCs) reproduce the main functions of the parental cells and therefore represent the ideal type of EVs for modulating the course of either disease. The aim of this review is to discuss the role of EVs in OA and RA focusing on their potential pathogenic effect and possible therapeutic options. Special attention is given to MSCs and MSC-derived EVs for modulating OA and RA progression with the perspective of developing innovative therapeutic strategies.
27916980 The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. 2017 Jan Patients with rheumatoid arthritis can be divided into two major subsets characterized by the presence versus absence of antibodies to citrullinated protein antigens (ACPAs) and of rheumatoid factor (RF). The antibody-positive subset of disease, also known as seropositive rheumatoid arthritis, constitutes approximately two-thirds of all cases of rheumatoid arthritis and generally has a more severe disease course. ACPAs and RF are often present in the blood long before any signs of joint inflammation, which suggests that the triggering of autoimmunity may occur at sites other than the joints (for example, in the lung). This Review summarizes recent progress in our understanding of this gradual disease development in seropositive patients. We also emphasize the implications of this new understanding for the development of preventive and therapeutic strategies. Similar temporal and spatial separation of immune triggering and clinical manifestations, with novel opportunities for early intervention, may also occur in other immune-mediated diseases.
28114971 Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease ac 2017 Jan 23 BACKGROUND: To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. METHODS: Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation. RESULTS: Compared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1β, IL-8), disability (IL-1β, IL-6), pain (IL-1β, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1β, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05). CONCLUSION: RA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.
28753954 Isoegomaketone Alleviates the Development of Collagen Antibody-Induced Arthritis in Male B 2017 Jul 19 In this study, we attempted to identify and assess effects of isoegomaketone (IK) isolated from Perilla frutescens var. crispa on the development of rheumatoid arthritis (RA). RA was induced in male Balb/c mice by collagen antibody injection. Experimental animals were randomly divided into five groups: normal, collagen antibody-induced arthritis (CAIA), CAIA + IK (5 mg/kg/day), CAIA + IK (10 mg/kg/day), and CAIA + apigenin (16 mg/kg/day) and respective treatments were administered via oral gavage once per day for four days. Mice treated with IK (10 mg/kg/day) developed less severe arthritis than the control CAIA mice. Arthritic score, paw volume, and paw thickness were less significant compared to the control CAIA mice at day seven (73%, 15%, and 14% lower, respectively). Furthermore, histopathological examination of ankle for inflammation showed that infiltration of inflammatory cells and edema formation were reduced by IK treatment. Similarly, neutrophil to lymphocyte ratio (NLR) in whole blood was lower in mice treated with IK (10 mg/kg/day) by 85% when compared to CAIA mice. Taken together, treatment with IK delays the onset of the arthritis and alleviates the manifestations of arthritis in CAIA mice.
28875224 The influence of fibromyalgia on achieving remission in patients with long-standing rheuma 2017 Dec To investigate the influence of fibromyalgia (FM) on achieving remission defined on the basis of the Simplified Disease Activity Index (SDAI) remission criteria in patients with long-standing rheumatoid arthritis (RA). This observational longitudinal cohort consisted of long-standing RA patients being treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs). After 6 months of follow-up, the patients fulfilling or not fulfilling the remission criteria were identified and compared with each other in terms of the presence of FM, neuropathic pain, and other comorbidities. At the end of the 6-month observation period, 24 of the 117 patients (20.4%) met the SDAI remission criteria. Logistic regression analysis showed that the modified Rheumatic Disease Comorbidity Index (mRDCI) (p = 0.0001), the FM presence (p = 0.0001), and the 36-item short-form health survey Mental Component Summary (SF-36 MCS) Score (p = 0.0088) were the strongest predictors of not being in SDAI remission. None of the patients with concomitant FM (17.1%) achieved SDAI remission. In comparison with the non-FM patients, the patients with RA and FM patients had worse scores on the SF-36 MCS (p = 0.011), on the sleep Visual Analogue Scale (VAS) (p = 0.018), on the self-counts of tender joints (p = 0.039), and on the PainDetect Questionnaire (PDQ) (p = 0.001). To avoid over treatment, an assessment of FM should be considered in RA patients who do not fulfil the remission criteria.
29198886 Remaining local subclinical joint inflammation is associated with deteriorated metacarpeal 2018 Oct OBJECTIVES: Bone alterations at the subchondral level during rheumatoid arthritis (RA) remain under investigation. It remains unknown whether subchondral bone damage might still occur in RA patients in clinical remission, which could then infer suggesting that even minor subclinical inflammatory changes in the joint can induce local bone loss. METHODS: Thirty-two RA patients treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) with low disease activity since at least 6 months and having erosion on the second or third metacarpeal head were enrolled in this pilot cross-sectional study. They were divided in two groups according to local inflammation assessed by Doppler-ultrasound exam surrounding the site of erosion. Cortical and trabecular parameters of the metacarpeal head were then assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) and compared in both groups. RESULTS: Twenty and twelve RA patients were enrolled in the "Doppler positive erosion" (DE+) group and Doppler negative erosion (DE-) group, respectively. No difference was observed in their clinical or biological RA characteristics. Both cortical density and thickness were similar among groups. Within the trabecular network, while no difference in bone volume was observed, trabecular density as well as trabecular number were decreased (P<0.001 and P<0.05 respectively), whereas trabecular separation and distribution of trabecular separation were increased in DE+ compared to DE- (P<0.05). CONCLUSION: In RA patients in low disease activity under bDMARDs, persistence of local inflammation was associated with alteration of the trabecular compartment. Trabecular density was the most strongly altered parameter and could be a candidate to assess drug effect on periarticular bone damage.
28615051 The pathway to consultation for rheumatoid arthritis: exploring anticipated actions betwee 2017 Jun 14 BACKGROUND: When people first experience symptoms of rheumatoid arthritis (RA) they often delay seeking medical attention resulting in delayed diagnosis and treatment. This research assesses behaviours people might engage in prior to, or instead of, seeking medical attention and compares these with behaviours related to illnesses which are better publicised. METHODS: Thirty-one qualitative interviews with members of the general public explored intended actions in relation to two hypothetical RA vignettes (with and without joint swelling) and two non-RA vignettes (bowel cancer and angina). The interviews were audio-recorded and transcribed. Analysis focused on intended information gathering and other self-management behaviours in the interval between symptom onset and help-seeking. RESULTS: Participants were more likely to envision self-managing symptoms when confronted with the symptoms of RA compared to the other vignettes. Participants would look for information to share responsibility for decision making and get advice and reassurance. Others saw no need for information seeking, perceived the information available as untrustworthy or, particularly in the case of bowel cancer and angina, would not want to delay seeking medical attention. Participants further anticipated choosing not to self-manage the symptoms; actively monitoring the symptoms (angina/ bowel cancer) or engaging in self-treatment of symptom(s). DISCUSSION: These results help define targets for interventions to increase appropriate help-seeking behaviour for people experiencing the initial symptoms of RA, such as educational interventions directed at allied healthcare professionals from whom new patients may seek information on self-management techniques, or the development of authoritative and accessible informational resources for the general public.
28791449 Incidence of inflammatory joint diseases in Finland: results from a population-based epide 2017 Oct The objective of the study was to assess the incidence of inflammatory joint diseases and possible environmental factors contributing to their occurrence in a defined population in Finland. All rheumatologists practising in the Northern Savo rheumatological outpatient departments collected data on their newly diagnosed patients with an inflammatory joint disease in 2010. Antibodies to Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) were determined from patients with various arthritides. The incidence of all arthritis cases was 141.8/100,000 (95% CI 126.1-159.1). Eighty-six patients, 43 men and 43 women, satisfied the ACR/Eular 2010 classification criteria for rheumatoid arthritis (RA) yielding an annual incidence of 41.6/100,000 (33.3-51.4), 42.5 (30.8-57.3) for men and 40.8 (29.9-56.1) for women. The incidence of chronic spondyloarthritides was 36.3 (28.6-45.5), reactive arthritis 7.8 (4.4-12.6), undifferentiated arthritis 38.7 (30.7-48.2), and crystalline arthritis 15.0 (10.2-21.3). Immunoglobulin A (IgA) antibody levels to Pg were higher among men, patients with anti-cyclic citrullinated peptide antibodies (ACPA) or missing teeth and AaIgA antibody levels in patients with missing teeth. In RA, 67 % of men and 35% of women had a smoking history, p = 0.012. There was no difference between the genders in the incidence of RA, which might be explained by a higher carriage of periodontal bacteria and a higher smoking rate among men. In other disease categories, the incidences were comparable to those earlier reported. By influencing behavioral and environmental factors, it might be possible to reduce the burden of ACPA-positive RA.
27914804 Nutrition and chronic inflammatory rheumatic disease. 2017 Oct Nutrition is a major environmental influence on human health. Epidemiological and interventional studies suggest a pathophysiological or therapeutic role, respectively, for nutrition in inflammatory rheumatic diseases (IRDs). Nevertheless, the associations between nutrition and IRDs are often weak and inconsistent, and the available clinical trials on nutrition are methodologically flawed. Experimental evidence is accumulating that micronutrients in the diet may influence intestinal and systemic immune responses via complex interactions involving the gut microbiota. Micronutrients may, therefore, contribute to the pathogenesis of inflammatory diseases. No interventions targeting these interactions for diagnostic, prophylactic, or therapeutic purposes have been developed to date. Moreover, the relevance to human disease of experimental results obtained in animals or in vitro is unclear. Novel high-throughput technologies (-omics) may prove useful for a systems biology approach to these results that takes the complexity of the interactions into account. Concomitant cohort studies combining clinical and laboratory data collected over time may provide new impetus to research into the connections between nutrition and IRDs.
28545441 Association between antibodies to carbamylated proteins and subclinical atherosclerosis in 2017 May 25 BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor.
28302011 The Pharmacological Mechanisms and Therapeutic Activities of Hydroxychloroquine in Rheumat 2017 Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies. These significant findings on HCQ suggest the potential therapeutic applications of HCQ for treatment of many diseases, such as cancers, skin disease, antiphospholipid syndrome, etc. This review focuses on recent in vitro and clinical trials on its pharmacological mechanisms, therapeutic activities, and potential adverse effects.
27941072 Is it time to revisit the role of ultrasound in rheumatoid arthritis management? 2017 Jan For over a decade, a large number of studies have highlighted the benefits of ultrasound (US) in the diagnosis and management of rheumatic diseases, especially rheumatoid arthritis (RA). However, its benefits in routine practice have been less studied and trials examining US as part of various clinical strategies are just emerging, with recent randomised trials examining the added value of US in tight-control paradigms. The conclusions of these trials have raised questions on the role of US in RA management. This Viewpoint analyses the recent studies, and discusses potential limitations in study designs as well as the methodological challenges of assessing the added value of an imaging technique.
28666478 Cardiovascular risk factors predate the onset of symptoms of rheumatoid arthritis: a neste 2017 Jun 30 BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD). Our aim was to evaluate the impact of factors related to CVD, such as smoking, lipid levels, hypertension, body mass index (BMI) and diabetes, in individuals prior to the onset of symptoms of RA. METHODS: A nested case-control study was performed including data from 547 pre-symptomatic individuals (i.e. individuals who had participated in population surveys in northern Sweden prior to onset of symptoms of RA, median time to symptom onset 5.0 (interquartile range 2.0-9.0) years) and 1641 matched controls. Within the survey, health examinations prior to symptom onset were performed, blood samples were analysed for plasma glucose and lipids, and data on lifestyle factors had been collected with a questionnaire. CVD risk factors were extracted and further analysed with conditional logistic regression models for association with subsequent RA development, including hypertension, apolipoprotein (Apo)B/ApoA1 ratio, BMI, diabetes and smoking habits. RESULTS: Smoking and BMI ≥ 25 (odds ratio (OR) (95% confidence interval (CI)) =1.86 (1.48-2.35) and OR = 1.28 (1.01-1.62), respectively) were associated with increased risk for future RA development. In women, elevated ApoB/ApoA1 ratio (OR = 1.36 (1.03-1.80)) and smoking (OR = 1.82 (1.37-2.41)) were significantly associated with being pre-symptomatic for RA, whilst in men smoking (OR = 1.92 (1.26-2.92)) and diabetes (OR = 3.62 (95% CI 1.13-11.64)) were significant. In older (>50.19 years) individuals, only smoking (OR = 1.74 (1.24-2.45)) was significantly associated with increased risk of future RA, whereas in younger individuals the significant factors were elevated ApoB/ApoA1 ratio (OR = 1.39 (1.00-1.93)), BMI ≥ 25.0 (OR = 1.45 (1.04-2.02)) and smoking (OR = 2.11 (1.51-2.95)). Pre-symptomatic individuals had a higher frequency of risk factors: 41.5% had ≥3 compared with 30.4% among matched controls (OR = 2.81 (1.78-4.44)). CONCLUSIONS: Several risk factors for CVD were present in pre-symptomatic individuals and significantly associated with increased risk for future RA. These factors differed in women and men. The CVD risk factors had a greater impact in younger individuals. These results urge an early analysis of cardiovascular risk factors for proposed prevention in patients with early RA.
28321492 Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients. 2017 May OBJECTIVE: To assess seroprevalence of anti-Toxoplasma gondii antibodies; both IgG and IgM in Egyptian rheumatoid arthritis (RA) patients versus a non-RA group and to compare anti-Toxoplasma antibodies seroprevalence among RA patients receiving traditional treatment and RA patients treated with biologic drug. METHODS: 60 RA patients and 60 healthy controls were enrolled in the study. Patients were categorized into two groups: one group included 30 patients receiving disease modifying anti-rheumatic drugs (DMARDs), while the other group included 30 patients receiving biologic agent, infliximab, a TNF-α antagonist. Serum samples of all investigated persons were examined for anti-Toxoplasma antibodies. RA activity markers including rheumatoid factor, anti-cyclic citrullinated protein antibodies, C reactive protein, ESR in addition to disease activity score 28 (DAS28) of RA patients were also evaluated to explore their association with Toxoplasma seropositivity. RESULTS: Anti-Toxoplasma IgG antibodies were detected among 46/60 RA patients (76.7%) versus 29/60 controls (48.3%), (p = 0.001). Anti-Toxoplasma IgG titre was higher among RA group [median, (range) = 232.940 (8.949-653.242) IU/ml] than among controls [median, (range) = 68.820 (2.450-318.945) IU/ml], (p < 0.001). No difference was detected among RA patients either on traditional or biologic treatment regarding anti-Toxoplasma IgG antibodies. No positive anti-Toxoplasma IgM was detected. A positive correlation was detected between anti-Toxoplasma IgG titre and disease activity markers. CONCLUSION: Higher seroprevalence of anti-Toxoplasma IgG antibodies among RA patients compared to controls reflects an association between latent Toxoplasma infection and RA. Our findings support previous studies and necessitate future large-scale studies to elucidate the exact role of Toxoplasma whether a trigger of autoimmunity in RA or an effect of immunosuppression.
29279493 Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder, Hodgkin Type, f 2018 Apr 15 A 59-year-old man with an 18-year history of rheumatoid arthritis who had been treated with steroids, methotrexate, and infliximab presented with a high-grade fever, cervical lymphadenopathy, and hepatosplenomegaly. Epstein-Barr virus (EBV) hepatitis was diagnosed based on the liver histology and EBV antibody titer. The symptoms improved temporarily, but five months later, the fever, skin rash, jaundice, and thrombocytopenia relapsed. Bone marrow and liver biopsies demonstrated infiltration with Reed-Sternberg cells. Based on these findings, the patient was diagnosed with other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD), Hodgkin lymphoma type. This case followed a rare clinical course, in that acute hepatitis preceded the diagnosis of OIIA-LPD.
28116513 Repeatability and response to therapy of dynamic contrast-enhanced magnetic resonance imag 2017 Sep OBJECTIVES: To determine the repeatability and response to therapy of dynamic contrast-enhanced (DCE) MRI biomarkers of synovitis in the hand and wrist of rheumatoid arthritis (RA) patients, and in particular the performance of the transfer constant K (trans) , in a multicentre trial setting. METHODS: DCE-MRI and RA MRI scoring (RAMRIS) were performed with meticulous standardisation at baseline and 6 and 24 weeks in a substudy of fostamatinib monotherapy in reducing synovitis compared with placebo or adalimumab. Analysis employed statistical shape modelling to avoid biased regions-of-interest, kinetic modelling and heuristic analyses. Repeatability was also evaluated. RESULTS: At early study termination, DCE-MRI data had been acquired from 58 patients in 19 imaging centres. K (trans) intra-subject coefficient of variation (N = 14) was 30%. K (trans) change demonstrated inferiority of fostamatinib (N = 11) relative to adalimumab (N = 10) after 6 weeks (treatment ratio = 1.92, p = 0.003), and failed to distinguish fostamatinib from placebo (N = 10, p = 0.79). RAMRIS showed superiority of fostamatinib relative to placebo at 6 weeks (p = 0.023), and did not distinguish fostamatinib from adalimumab at either 6 (p = 0.175) or 24 (p = 0.230) weeks. CONCLUSION: This demonstrated repeatability of K (trans) and its ability to distinguish treatment groups show that DCE-MRI biomarkers are suitable for use in multicentre RA trials. KEY POINTS: • DCE-MRI biomarkers are feasible in large multicentre studies of joint inflammation. • DCE-MRI K (trans) showed fostamatinib inferior to adalimumab after 6 weeks. • K (trans) repeatability coefficient of variation was 30% multicentre.
29247125 Incidence of hip and knee replacement in patients with rheumatoid arthritis following the 2018 May OBJECTIVES: To study the impact of the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and associated rheumatoid arthritis (RA) management guidelines on the incidence of total hip (THR) and knee replacements (TKR) in Denmark. METHODS: Nationwide register-based cohort and interrupted time-series analysis. Patients with incident RA between 1996 and 2011 were identified in the Danish National Patient Register. Patients with RA were matched on age, sex and municipality with up to 10 general population comparators (GPCs). Standardised 5-year incidence rates of THR and TKR per 1000 person-years were calculated for patients with RA and GPCs in 6-month periods. Levels and trends in the pre-bDMARD (1996-2001) were compared with the bDMARD era (2003-2016) using segmented linear regression interrupted by a 1-year lag period (2002). RESULTS: We identified 30 404 patients with incident RA and 297 916 GPCs. In 1996, the incidence rate of THR and TKR was 8.72 and 5.87, respectively, among patients with RA, and 2.89 and 0.42 in GPCs. From 1996 to 2016, the incidence rate of THR decreased among patients with RA, but increased among GPCs. Among patients with RA, the incidence rate of TKR increased from 1996 to 2001, but started to decrease from 2003 and throughout the bDMARD era. The incidence of TKR increased among GPCs from 1996 to 2016. CONCLUSION: We report that the incidence rate of THR and TKR was 3-fold and 14-fold higher, respectively among patients with RA compared with GPCs in 1996. In patients with RA, introduction of bDMARDs was associated with a decreasing incidence rate of TKR, whereas the incidence of THR had started to decrease before bDMARD introduction.