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ID PMID Title PublicationDate abstract
30987884 Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoi 2021 Jan OBJECTIVES: Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). METHODS: We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3-6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. RESULTS: This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. CONCLUSIONS: Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.
33681846 Rheumatoid arthritis is associated with increased symptomatic acromial and scapular spine 2021 Mar BACKGROUND: The purpose of this study was to determine factors associated with early symptomatic acromial and scapular spine fractures in patients who underwent reverse total shoulder arthroplasty (RTSA). METHODS: We retrospectively evaluated all RTSAs performed by the senior author between 1/1/2013 and 6/1/2019. We evaluated patient demographics including gender, age, prevalence of comorbidities including osteoporosis, inflammatory arthritis, diabetes, and endocrine disorders such as hypothyroidism. We also evaluated preoperative and 2-week postoperative radiographs for center of rotation medialization (CORM) as distance between the center of the humeral head or glenosphere and the line of the deltoid, and distalization via the acromial-greater tuberosity distance (AGT). We evaluated inter- and intra-rater reliability via intraclass correlation coefficients. RESULTS: We included 335 RTSAs with a minimum of 3 months of follow-up in the analysis. Reliability was acceptable with all intraclass correlation coefficients> 0.75. Symptomatic acromial and scapular spine stress fractures were significantly more common in those with inflammatory arthritis than those without (18% vs. 5%, P = 0.016). The rate of fracture was highest in patients with rheumatoid arthritis (24% vs. 5.2%, P = 0.003). There was no statistically significant association between symptomatic fractures and preoperative CORM or AGT (P = 0.557, P = 0.528) or postoperative CORM or AGT (P = 0.56, P = 0.102). There also was no statistically significant correlation between symptomatic stress fracture and patient age, gender, BMI, smoking, osteoporosis, gout, medical comorbidity, or previous shoulder surgery. CONCLUSION: In this retrospective analysis of postoperative RTSA, symptomatic acromial and scapular stress fractures were significantly more common in patients with rheumatoid arthritis and thus precautions should be taken in these patients.
34482531 Disrupted homeostasis of synovial hyaluronic acid and its associations with synovial mast 2021 Dec Hyaluronic acid (HA) is the main component of the extracellular matrix (ECM) of joints, and it is important for a lubricating joint during body movement. Degradation is the main metabolic process of HA in vivo. Hyaluronidases (HAase) were known for HA degradation. The inflammation-induced HA rapid-metabolism can reduce HA viscosity and concentration in joints. Mast cells (MC) containing their specific proteases were found in synovium tissue. It is unclear if MC-proteases could be involved in HA degradation pathways. This study aims to explore the correlations between HA concentration vs mast cell proteases, or matrix metalloproteinase-2/9 (MMP-2/9) and to investigate the association of MC-specific proteases with disrupted synovial HA homeostasis in rheumatoid arthritis (RA) or collagen-induced arthritis rats. The synovial fluid samples from no-RA and RA patients were collected; the collagen-induced arthritis (CIA) rat model was established; HA concentration and the activities of MC-protease and MMP-2/9 in the samples were detected, and the correlations were analyzed. In vitro interaction experiment was carried out by mixing MC-proteases with HA to observe the degradation speed. The HA concentrations in synovial fluids were decreased in RA patients and CIA rats compared with those in no-RA subjects or normal rats respectively. The activities of mast cell proteases in synovial fluids were increased and positively correlated with MMP-9, but negatively correlated with HA concentrations. In vitro study, the addition of MC-chymase and tryptase promoted the speed in HA degradation. MC-proteases may influence HA degradation pathway.
33379867 Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Ta 2021 Jan 13 Rheumatoid arthritis (RA) is an angiogenic and chronic inflammatory disease. One of the most extensively used first-line drugs against RA is methotrexate (MTX), but it shows poor solubility, short in vivo circulation, and off-target binding, leading to strong toxicity. To overcome these shortcomings, the present study loaded MTX into nanoparticles of human serum albumin modified with mannose (MTX-M-NPs) to target the drug to neutrophils. MTX-M-NPs were prepared, and their uptake by neutrophils was studied using laser confocal microscopy and flow cytometry. A chick chorioallantoic membrane assay was used to assess their ability to inhibit angiogenesis. The pharmacokinetics and tissue distribution of MTX-M-NPs were investigated using fluorescence microscopy and high-performance liquid chromatography. Their pharmacodynamics was evaluated in a rat model with arthritis induced by collagen. Neutrophils took up MTX-M-NPs significantly better than the same nanoparticles (NPs) without mannose. MTX-M-NPs markedly suppressed angiogenesis in chick embryos, and the MTX circulation was significantly longer when it was delivered as MTX-M-NPs than as a free drug. MTX-M-NPs accumulated mainly in arthritic joints. The retention of NPs was promoted by mannose-derived coating in arthritic joints. Serum levels of inflammatory cytokines, joint swelling, and bone erosion were significantly decreased by MTX-M-NPs. In conclusion, these NPs can prolong the in vivo circulation of MTX and target it to the sites of inflammation in RA, reducing drug toxicity. MTX-M-NPs allow the drug to exert its intrinsic anti-inflammatory, antiangiogenic, and analgesic properties, making it a useful drug delivery system in RA.
35096892 Anti-citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Pr 2021 Anti-citrullinated protein antibodies (ACPAs) are autoantibodies commonly observed in patients with rheumatoid arthritis (RA). Currently, most of the mechanisms of ACPA formation and bone destruction are well-understood, however, some unknown mechanisms still exist. There have been many new advances in ACPA-related clinical applications and targeted therapies. However, the existence of different ACPA subtypes is a limitation of targeted therapy. Herein, we present an overview of the process of ACPA generation, the underlying pathogenesis, and relevant clinical application and prospects.
34782021 Development of the Rheumatoid Arthritis Distress Scale (RADS): a new tool to identify dise 2021 Nov 16 BACKGROUND: Patients with Rheumatoid Arthritis (RA) may experience psychological distress (depression, anxiety) in addition to their physical symptoms. People with RA may also experience disease-specific distress (DSD), related to the specific burden of living with their life-long condition. DSD is a patient reported outcome in several long-term conditions, including type 1 and 2 diabetes. The aims of this study were to determine whether DSD is experienced by people with RA, and if so, develop a Patient Reported Outcome Measure (PROM) to assess for DSD in people with RA. METHODS: A five-phased qualitative study was conducted which consisted of a secondary data analysis of 61 interviews of people with rheumatological disease (Phase 1), validation of findings via a Patient and Public Involvement (PPI) group of people with RA (n = 4) (Phase 2), item generation for a PROM (Phase 3) and establishing face and content validity of the PROM via PPI group (n = 4) and individual cognitive interviews (n = 9) of people with RA respectively (Phase 4 and 5). The final PROM was presented at a Patient Education Evening for patients with long-term rheumatological conditions, including RA, and carers. RESULTS: Five themes of rheumatological disease distress emerged from Phase 1, which were validated in the Phase 2 PPI group. After Phases 3-5, the Rheumatoid Arthritis Distress Scale (RADS) was formed of 39 items and 3 supplementary questions. Overall participants reported the content of the RADS to be clear and relevant, and that DSD is a valid concept in RA, distinct from other entities like clinical depression or anxiety. CONCLUSIONS: DSD appears to be an important concept in RA. The 39-item RADS demonstrates acceptable face and content validity in this patient group. Further psychometric testing is needed. The RADS may be a useful tool for healthcare professionals to identify RA distress.
33737964 Epidemiology of cardiac or orthopedic procedures in gout versus rheumatoid arthritis: a na 2021 AIMS: To examine the secular trends in the number and rates of in-hospital cardiac and orthopedic procedures in people with gout and rheumatoid arthritis (RA), and the United States (US) general population, from 1998 to 2014. METHODS: We examined the frequency of seven common cardiac and orthopedic procedures in hospitalized people with gout, RA, or the general population using the 1998-2014 US National Inpatient Sample (NIS). Poisson regression evaluated the differences in frequencies in 1998 versus 2014, between gout and RA, and within each cohort. RESULTS: Both in-hospital cardiac and orthopedic procedures increased in gout and RA with time, in contrast with declining cardiac procedures in the general US population. Cardiac procedures were significantly higher in gout versus RA in 1998 (59% higher) and 2014 (92% higher). The rate of cardiac procedures increased from 36.6 to 82.8 in gout and from 20.1 to 33.1 in RA per 100,000 NIS claims from 1998 to 2014. Orthopedic procedures became more common than cardiac procedures in gout and RA by 2014. In RA, the cardiac-orthopedic procedure volume difference was significant in 1998 and 2014. We noted no significant difference between cardiac versus orthopedic procedures in 1998 in gout, but the difference was significant in 2014. Orthopedic procedures in gout were significantly lower than RA in 1998 (33% lower), but were significantly higher than RA in 2014 (5% higher). CONCLUSION: Increasing in-hospital cardiac procedures in gout and RA contrasting with declining general US population rates indicated that optimal management of systemic inflammation and an early diagnosis of gout and RA are needed. The rate of increase in orthopedic procedures exceeded that in cardiac procedures. A much greater volume and rate of increase in common in-hospital cardiac and orthopedic procedures in gout compared to RA indicates that an aggressive approach to treat-to-target in gout is needed to potentially reduce the associated healthcare burden and cost. PLAIN LANGUAGE SUMMARY: Cardiac and orthopedic procedures rising faster for gout compared to rheumatoid arthritis in the United States We performed a national US study of the most common cardiac versus orthopedic procedures from 1998 to 2014. We found that over time, the number and the rate of cardiac procedures increased in people with gout (2.2-fold higher) or rheumatoid arthritis (1.6-fold higher). This was surprising, since during the same time, we noted a decrease in cardiac procedures in the general U.S. population. The rate of cardiac procedures in gout was 2.5-fold higher than that in rheumatoid arthritis, 82.8 vs. 33.1 per 100,000 NIS claims in 2014. Interestingly, orthopedic procedures were more common than cardiac procedures in both gout and RA in all periods. Also, the difference in the numbers of cardiac vs. orthopedic procedures increased over time in both gout and RA. Gout outpaced rheumatoid arthritis for both the total number and the rate of cardiac or orthopedic procedures over time. Therefore, our study provides an understanding of an increasing procedure burden in gout compared to rheumatoid arthritis, and to the general U.S. people with these conditions.
34447906 A Novel Hypothetical Approach to Explain the Mechanisms of Pathogenicity of Rheumatic Arth 2021 Jun The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibodies are deposited in the joint via the activity of highly cationic histones released from neutrophil extracellular traps (NETs) in a phenomenon termed NETosis. The cationic histones function as opsonic agents that bind to negatively charged domains in autoantibodies and complement compounds via strong electrostatic forces, facilitating their deposition and endocytosis by synovial cells. However, eventually the main cause of tissue damage is the plethora of toxic pro-inflammatory substances released by activated neutrophils recruited by cytokines. Tissue damage in RA can also be accompanied by infections which, upon bacteriolysis, release cell-wall components that are toxic to tissues. Some amelioration of the damaged cells and tissues in RA may be achieved by the use of highly anionic heparins, which can neutralize cationic histone activity, provided that these polyanions are co-administrated with anti-inflammatory drugs such as steroids, colchicine, or methotrexate, low molecular weight antioxidants, proteinase inhibitors, and phospholipase A2 inhibitors.
34080972 Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cel 2021 Jun 3 Epstein-Barr virus (EBV) infection is associated with rheumatoid arthritis (RA) in adults, though the nature of the relationship remains unknown. Herein, we have examined the contribution of viral infection to the severity of arthritis in mice. We have provided the first evidence that latent gammaherpesvirus infection enhances clinical arthritis, modeling EBV's role in RA. Mice latently infected with a murine analog of EBV, gammaherpesvirus 68 (γHV68), develop more severe collagen-induced arthritis and a Th1-skewed immune profile reminiscent of human disease. We demonstrate that disease enhancement requires viral latency and is not due to active virus stimulation of the immune response. Age-associated B cells (ABCs) are associated with several human autoimmune diseases, including arthritis, though their contribution to disease is not well understood. Using ABC knockout mice, we have provided the first evidence that ABCs are mechanistically required for viral enhancement of disease, thereby establishing that ABCs are impacted by latent gammaherpesvirus infection and provoke arthritis.
34222666 Knee alterations in rheumatoid arthritis: Comparison of US and MRI. 2021 OBJECTIVE: This study was designed to compare the diagnostic efficacy of ultrasonography (US) and magnetic resonance imaging (MRI) in detecting changes in the knee of patients with rheumatoid arthritis (RA) and discover the possible association between the serological index and bone erosion detected by US. PATIENTS AND METHODS: In this retrospective study, the US images and MRI findings of the knee in patients with RA from December 2017 to January 2020 were evaluated. Diagnostic outcomes were compared. The rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, and anti-cyclic citrullinated peptide antibody (ACPA) levels of the patients were recorded. The relation between laboratory index and US findings was analyzed by multivariable logistic regression. RESULTS: US showed remarkable accuracy, sensitivity, and specificity in diagnosing synovitis, bone erosion, and soft tissue swelling. In terms of reliability, the agreement between US and MRI was moderate to almost perfect. Meanwhile, a positive association between ACPA level and bone erosion was observed in patients with RA. CONCLUSIONS: US may have a role as the initial imaging modality in patients with RA. Patients with higher ACPA levels may need more active treatment because they are more likely to have bone erosion detected by US.
32491741 Sulfasalazine. 2022 Jan Sulfasalazine is a disease-modifying antirheumatic drug (DMARD) used in the treatment and management of autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease. This activity reviews the indications, contraindications, mode of action, adverse events, and other key elements of sulfasalazine therapy in the clinical setting as relates to the essential points needed by members of an interprofessional team managing the care of patients with inflammatory bowel disease and rheumatoid arthritis and its related conditions and sequelae.
35118335 Tracheal laceration causing important post-intubation delayed subcutaneous emphysema and v 2021 A 68-year-old man with a background of severe active rheumatoid arthritis (RA) was admitted to Intensive Care Unit (ICU) for respiratory support due to COVID-19 infection. Two days after an elective and uneventful intubation he developed severe and worsening surgical emphysema affecting his face, neck and both upper limbs. Ventilation was difficult to be achieved. Based on a negative chest X-ray, a CT scan of the chest was organized which showed extensive pneumomediastinum with no obvious cause. Therefore, urgent bronchoscopy was performed which showed a glassy lesion/laceration measuring 2 cm × 2 cm at the level of mid-trachea but no other signs of penetration through the airways were noted. Since events appeared 2 days after intubation, this was perceived as secondary to trauma during intubation on an inflammatory process background from RA and COVID-19 in the airways. The endotracheal tube was progressed beyond the site of laceration and bilateral pectoral fasciotomies were performed with negative suction vacuum dressings, which was successful in decreasing the surgical emphysema and achieving decreased ventilation requirements. Despite multi-organ support the patient continued to deteriorate and unfortunately passed away a week following admission. This scenario hightlighted that endotracheal sequalae should be suspected in patients with similar background and presentation.
34277168 Microbiome in Rheumatoid Arthritis and Celiac Disease: A Friend or Foe. 2021 Jun Rheumatoid arthritis (RA) and celiac disease (CD) are both autoimmune diseases with increasing global prevalence. These two diseases have been connected based on similar HLA mutations, serological markers, rheumatological, and gastrointestinal manifestations. In this review, we discuss the role of the oral and gut microbiome in the development and progression of RA and CD. Here, we highlight similar microbial dysbiosis and how these alterations in composition can lead to worsening disease severity in both CD and RA. Additionally, we analyze the role of probiotics in regulating the microbiome and improving symptoms associated with RA and CD.
34181704 The COVID-19 pandemic: an increased risk of rheumatoid arthritis. 2021 Jun COVID-19 is a respiratory infection similar to viral pneumonia and is caused by SARS-CoV-2. Chloroquine and hydroxychloroquine make up the major part of the treatment regimen for the management of COVID-19 infections, which are also commonly used in treatment of patients with malaria as well as autoimmune diseases like rheumatoid arthritis (RA). In this review, we analyzed the scientific evidences pertaining to any possible association of SARS-CoV-2 infection with RA. We thus believe that people predisposed to RA carry a higher infection risk than the general population both due to the iatrogenic effects of the RA related drug therapy. Thus COVID-19 pandemic may bring a higher risk of health emergency in complex diseases such as RA.
34897497 Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis. 2021 Sep 13 OBJECTIVES: To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). METHODS: Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. RESULTS: Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. CONCLUSIONS: This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.
34865103 Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures. 2021 Dec 3 OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. METHODS: Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. RESULTS: Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015-7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195-33.292; P=0.030). CONCLUSIONS: Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.
34791411 Surgical Treatment of Wrist Joint Dysfunction in Rheumatoid Arthritis: A Report of Two Cas 2021 Nov 18 In rheumatoid arthritis (RA), it is important to actively treat wrist dysfunction to improve patient outcomes. Herein, we report two cases of wrist dysfunction in RA patients who required partial wrist fusion soon after drug initiation. [Case 1] A 38-year-old woman was referred to our hospital because of left wrist joint pain. At the time of examination, swelling and tenderness of the left wrist joint were observed. After 6 months of medication, no improvement in symptoms was noted; therefore, partial wrist fusion was performed. [Case 2] A 38-year-old woman was referred to our hospital because of right wrist joint pain. A plain X-ray image showed fusion of the carpal bones. Due to previous failure of drug treatment, the patient opted for arthrodesis. The postoperative course was good in both cases, and the pain improved. In these cases of monoarthritic RA, synovitis and bone destruction were observed, but blood tests showed no features of active disease, and drug treatment was ineffective. In such cases, early surgical treatment should be considered, rather than continuing conservative treatment, to ensure the best outcomes.
34065413 Iguratimod: Novel Molecular Insights and a New csDMARD for Rheumatoid Arthritis, from Japa 2021 May 20 Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), thereby suppressing the production of immunoglobulin and inhibiting the activity of nuclear factor kappa-light chain enhancer of activated B cells. In Japan, it is one of the most used csDMARDs in daily practice, but it is not recommended as a treatment for RA due to the lack of large-scale evidence established overseas. However, recent reports on the novel pharmacological effects of IGU on lymphocytes and synovial fibroblasts, as well as its efficacy in daily practice, have increased its importance as a drug for the treatment of RA. In this review, we highlighted the basic and clinical studies in IGU and discuss its potential as a new therapeutic agent for the treatment of RA.
34045887 Correlation Between Level of Interleukin-37 and Rheumatoid Arthritis Progression. 2021 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that primarily affects joints. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that is known to suppress immune response and inflammation. The objective of this study is to evaluate the correlation between level of IL-37 and RA progression using the disease activity score in 28 joints (DAS-28). METHODS: A total of 87 RA patients were separated into 4 groups based on the DAS28, referred to as the remission, mild, moderate and severe groups. 18 healthy volunteers were also included. Serum level of IL-37 and IL-37 mRNA expression level in peripheral blood mononuclear cells (PBMCs) in each individual participant as well as IL-37 mRNA expression level in synovial cells were assessed to explore their correlation with RA progression. RESULTS: Serum level of IL-37 and IL-37 mRNA expression levels in both PBMCs and synovial cells were all positively correlated with the severity of RA as reflected by the DAS28. Receiver operating characteristic (ROC) analysis revealed area under curve (AUC) values of 1, 0.5262 and 0.7789 for the three parameters. CONCLUSION: Our results suggest that serum IL-37 level and mRNA expression levels of IL-37 in PBMCs and synovial cells are correlated with the severity of RA in a Chinese population.
34028145 Epstein-Barr virus-related lymphoma in rheumatoid arthritis: implications for long-term us 2021 May 24 BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease where methotrexate (MTX) is widely used as the first-line therapy. The combination of RA and MTX is associated with lymphoproliferative disorders (LPD). RA patients with Epstein-Barr virus (EBV) have impaired T-lymphocyte function, thus allowing an overgrowth of EBV-positive lymphoblastoid cells. We examined the association of EBV with LPD in immunosuppressed RA patients, particularly those treated with MTX. AIM: To review the relationship between RA, EBV-associated LPD and MTX use. METHODS: We reported two cases of RA patients with long-term MTX treatment who subsequently developed EBV-positive LPD, followed by a review of the relevant literature. RESULTS: Compared with normal population, RA patients have a higher risk of lymphoma, with diffuse large B-cell lymphoma being the most common subtype. MTX withdrawal can lead to lymphoma regression. Other biological therapies, such as abatacept and tocilizumab, are not associated with increased EBV-positive lymphoma diagnosis in RA patients. CONCLUSION: The association between EBV, lymphoma and MTX highlights the need to consider reducing or stopping MTX in patients who have had stable RA for many years.