Infection In Rheumatoid Arthritis Patients Research Articles

Nature of the Association between Rheumatoid Arthritis and Cervical Cancer and Its Potential Therapeutic Implications.

It is now established that patients with rheumatoid arthritis (RA) have an increased risk of developing cervical cancer (CC) or its precursor, cervical intraepithelial neoplasia (CIN). However, the underlying mechanisms of this association have not been elucidated. RA is characterized by unresolved chronic inflammation. It is suggested that human papillomavirus (HPV) infection in RA patients exacerbates inflammation, increasing the risk of CC. The tumor microenvironment in RA patients with CC is also marked by chronic inflammation, which aggravates the manifestations of both conditions. Gut and vaginal dysbiosis are also considered potential mechanisms that contribute to the chronic inflammation and aggravation of RA and CC manifestations. Numerous clinical and pre-clinical studies have demonstrated the beneficial effects of various nutritional approaches to attenuate chronic inflammation, including polyunsaturated fatty acids and their derivatives, specialized pro-resolving mediators (SPMs), probiotics, prebiotics, and certain diets. We believe that successful resolution of chronic inflammation and correction of dysbiosis, in combination with current anti-RA and anti-CC therapies, is a promising therapeutic approach for RA and CC. This approach could also reduce the risk of CC development in HPV-infected RA patients.

Incidence Rates of Infections in Rheumatoid Arthritis Patients Treated with Janus Kinase or Interleukin-6 Inhibitors: Results of a Retrospective, Multicenter Cohort Study.

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48-9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87-10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups.

Factors associated with severe infection in rheumatoid arthritis patients: lessons learned from the COVID-19 pandemic.

This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients. Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated. Multivariate analysis identified history of previous serious infection, age > 60years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P < 0.001 and 0.003; respectively). Age > 60years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare.

Effect of tumour necrosis factor-a inhibitors exposure on surgical site infections in rheumatoid arthritis patients undergoing elective orthopaedic surgery: A meta-analysis.

A meta-analysis investigation was executed to evaluate the effect of tumour necrosis factor-a inhibitor exposure on surgical site infections in rheumatoid arthritis patients undergoing elective orthopaedic surgery. A comprehensive literature investigation till October 2023 was applied, and 82 470 individuals with orthopaedic surgery were in the chosen investigations' starting point. Odds ratio (OR) in addition to 95% confidence intervals (CIs) was utilized to compute the value of the effect of tumour necrosis factor-a inhibitors exposure on surgical site infections in rheumatoid arthritis patients undergoing elective orthopaedic surgery by the dichotomous approaches and a fixed or random model. Tumour necrosis factor uses had significantly higher surgical site infections (OR, 1.65; 95% CI, 1.21-2.25, p = 0.001) compared with tumour necrosis factor non-use in rheumatoid arthritis patients undergoing elective orthopaedic surgery. However, no significant difference was found between discontinued and continued tumour necrosis factor on surgical site infections (OR, 0.61; 95% CI, 0.35-1.05, p = 0.07) in rheumatoid arthritis patients undergoing elective orthopaedic surgery.Significantly higher surgical site infections was found comparing tumour necrosis factor uses to non-use; however, no significant difference was found between discontinued and continued tumour necrosis factor on surgical site infections in rheumatoid arthritis patients undergoing elective orthopaedic surgery. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine.

Objectives: We aimed to analyse the incidence and severity of breakthrough infections (BIs) in rheumatoid arthritis (RA) patients after a COronaVIrus Disease 2019 (COVID-19) vaccination booster dose. Methods: We enrolled 194 RA patients and 1002 healthcare workers (HCWs) as controls. Clinical, lifestyle and demographic factors were collected at the time of the third dose, and immunogenicity analyses were carried out in a subgroup of patients at 4-6 weeks after the third dose. Results: BIs were experienced by 42% patients (82/194) with a median time since the last vaccination of 176 days. Older age (>50 years; aHR 0.38, 95% CI: 0.20-0.74), receiving conventional synthetic disease modifying antirheumatic drugs (csDMARDs) (aHR 0.52, 95%CI: 0.30-0.90) and having a titre of neutralising antibodies >20 (aHR 0.36, 95% CI: 0.12-1.07) were identified as protective factors. Conversely, anti-IL6R treatment and anti-CD20 therapy increased BI probability. BIs were mostly pauci-symptomatic, but the hospitalisation incidence was significantly higher than in HCWs (8.5% vs. 0.19%); the main risk factor was anti-CD20 therapy. Conclusions: Being older than 50 years and receiving csDMARDs were shown to be protective factors for BI, whereas anti-IL6R or anti-CD20 therapy increased the risk. Higher neutralising antibody titres were associated with a lower probability of BI. If confirmed in a larger population, the identification of a protective cut-off would allow a personalised risk-benefit therapeutic management of RA patients.

Abstract 17 — Overall Infection Risks of Tofacitinib in Patient with Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials

Background There is an ongoing controversy surrounding whether tofacitinib increases the risk of infections in patients with rheumatoid arthritis (RA). To address this issue, we conducted a meta-analysis using data from randomized clinical trials (RCTs) to assess the overall risk of infection in these patients. Methods We conducted a comprehensive systematic search in EMBASE, MEDLINE, and CENTRAL from their inception until December 2022 to identify relevant RCTs reporting the occurrence of infections in patients with RA who were treated with the standard clinical therapeutic dosage of tofacitinib (5mg twice daily orally). The primary outcomes of the included studies in this review focused on the incidence of total infections, serious infections, non-serious infections, and opportunistic infections (including herpes zoster and tuberculosis). Additionally, we examined secondary outcomes related to the incidence of various sites of infections, including the upper respiratory tract, lower respiratory tract, gastrointestinal tract, hepatobiliary system, urinary tract, skin and soft tissue, blood, dental and oral soft tissue, genital, reproductive tract, bone and joint, and central nervous system infections. Due to the expected anticipation of clinical and methodological heterogeneity across studies, the effect estimate was pooled with a random-effects model, to obtain the RRs and 95% CIs, using Mantel-Haenszel statistical method. Results Twelve eligible RCTs, involving a total of 6,056 patients, were included in the analysis. In comparison to the control group (placebo and other active treatments), tofacitinib exhibited a significant increase in the risk of total infections (RR, 1.21; 95% CI, 1.07-1.37; I2, 28%), serious infections (RR, 1.23; 95% CI, 1.02-1.48; I2, 0%), non-serious infections (RR, 1.20; 95% CI, 1.05-1.36; I2, 29%), and opportunistic infections (RR, 1.66; 95% CI, 1.40-1.97; I2, 0%). Secondary outcomes analyses revealed a significant increase in the risk of lower respiratory infections with tofacitinib (RR, 1.27; 95% CI, 1.10–1.47; I2, 0%). Conclusion Compared with placebo and other active treatments, tofacitinib significantly increased the overall risk of infections (total infections, serious infections, non-serious infections, and opportunistic infections). These findings can help clinicians assess the risk of infections in RA patients treated with tofacitinib.

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis: A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register.

Janus Kinase inhibitors (JAKis) are targeted synthetic disease-modifying antirheumatic drugs and represent an important alternative to treat patients with moderate to high rheumatoid arthritis (RA) disease activity. Safety concerns associated with increased risk for venous thromboembolism (VTE), serious viral infection, and, more recently, major adverse cardiovascular events (MACE) in JAKi users have emerged worldwide. However, as the exact mechanisms to explain these safety concerns remain unclear, the increased risk of VTE, MACE, and serious viral infection in JAKi users is heavily debated. In light of the need to enrich the safety profile of JAKis in real-world data, we aim to quantify the incidence and risk of MACE, VTE, and serious viral infections in RA patients registered in the Danish DANBIO registry, a nationwide registry of biological therapies used in rheumatology. Therefore, we will conduct a population-based cohort study using a prevalent new-user design. We will identify all RA patients in the DANBIO, ≥ 18 years old, receiving a JAKi or a tumor necrosis factor α inhibitor (TNF-αi) from January 2017 to December 2022. Prevalent and new users of JAKis will be matched to TNF-αi comparators with similar exposure history using time-conditional propensity scores (TCPS). We will describe the cumulative incidence of the outcomes (VTE, MACE, serious viral infection) in each exposure group (JAKi users; TNF-αi users), stratified by outcome type. Additionally, the Aalen-Johansen method will be used to estimate the time-to-event survival function stratified by outcome type. We will also estimate the hazard ratio (HR) with 95% confidence interval (CI) of each outcome in both exposure groups using the time-dependent Cox proportional hazards model. Results will enrich the safety profile of JAKis in real-world data.

Study of the Effect of Treatment of Helicobacter pylori Infection in Rheumatoid Arthritis Patients

Objective: To assess the disease activity after treatment of Helicobacter pylori infection in rheumatoid arthritis patients at a tertiary care hospital of Rawalpindi.&#x0D; Study Design: Comparative cross-sectional study.&#x0D; Place and Duration of Study: Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jun to Nov 2021.&#x0D; Methodology: A total of 197 adult patients diagnosed with rheumatoid arthritis and with symptoms of dyspepsia were inducted into this study. First, the disease activity was measured considering parameters such as clinical swollen and tender joints count, disease activity scores 28(DAS-28), visual analogue scale (VAS) and laboratory parameters like erythrocyte sedimentation rate at the start as the baseline. Then, these were repeated after six months, and the differences between the two groups were compared.&#x0D; Results: At the start of the study, patients who were positive for H. pylori had markedly more swollen and tender joint counts and raised ESR values than those in the negative group. In addition, the disease activity score of 28 and pain scores was markedly raised in the positive group. After H. pylori eradication, the H. pylori-positive patients differed significantly (p&lt;0.001) from patients group negative for H. pylori infection in terms of improvement in DAS-28 score, visual analogue score and clinically. Laboratory indices like ESR showed significantly decreased values (p&lt;0.001) in the H. pylori-treated group compared to those not infected with H. pylori.&#x0D; Conclusion: From our results, it is suggested that H. pylori infection has a role in the pathogenesis of rheumatoid arthritis.

Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders

BackgroundOther iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA).MethodsWe investigated the clinicopathological characteristics, Epstein–Barr virus (EBV) infection, genetic findings, therapeutic response, and prognostic factors in 21 RA patients with OIIA TNK-LPDs and compared these with those of 39 with OIIA B-cell LPDs (B-LPDs) and 22 with non-OIIA B-LPDs.ResultsImmunohistologically, 11 patients (52%) showed CD4+ T-LPDs, and 7 had a T follicular helper (TFH) phenotype. The other nine patients (43%) showed CD8+ T-LPDs, and the remaining one (5%) had features of CD3+ CD4− CD8− nasal type TNK-cell lymphoma. CD30+, p53+, and CMYC+ atypical lymphocytes were identified in seven (33%), eight (38%), and five (24%) patients, respectively. In situ hybridisation detected EBV-encoded RNA (EBER) + large atypical lymphocytes in five patients (24%). Nine of 17 patients (53%) showed clonal peaks of TCRγ by polymerase chain reaction. Withdrawal of MTX and biologic drugs was effective in 12 patients (57%), and 8 (38%) received chemotherapies. Two patients with TFH+ or EBV+ CD4+ CD30+ large cell peripheral T-cell lymphoma, one with CD8+ systemic anaplastic large cell lymphoma, and two with systemic EBV+ CD8+ T-cell lymphoma of childhood showed a lethal progressive clinical course within 13 months. Moreover, > 500 U/L LDH, large atypical lymphocytes, expression of CD30, p53, and CMYC, and EBER+ atypical lymphocytes were significantly poor prognostic factors for overall survival (p < 0.05). Median interval from RA onset to OIIA TNK-LPDs was 72 months, which was shorter than 166 months in OIIA B-LPDs (p = 0.003). EBV+ atypical and reactive lymphocytes were frequently found in 15 patients with OIIA TNK-LPDs (71%), in 27 with OIIA B-LPDs (69%), and only in 3 with non-OIIA B-LPDs (14%).ConclusionsOIIA TNK-LPDs occurred in early phase of RA, compared with OIIA B-LPDs, and occasionally showed a lethal progressive clinical course. Detection of OIIA TNK-LPD patients with poor prognostic factors is necessary. EBV infection in immunosuppressed patients due to persistent RA, MTX, and biologic drugs may play a role in forming the tumour microenvironment and lymphomagenesis of TNK-LPDs.

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

Identification of lipopolysaccharide‐binding protein as a novel citrullinated autoantigen in rheumatoid arthritis

AbstractBackgroundA specific feature of the autoimmune response in rheumatoid arthritis (RA) is the presence of anti‐citrullinated protein antibodies (ACPAs) in patient sera. These antibodies can appear several years before disease onset and are involved in the development of RA.ObjectiveWe performed proteomic analysis by mass spectroscopy to identify novel citrullinated antigens and autoantibodies in RA patients.MethodsPolypeptides isolated from the sera of RA patients were identified by Orbitrap high‐precision mass spectrometry and then citrulline‐containing proteins were selected. The levels of ACPAs against these newly identified citrullinated autoantigens in sera of 100 RA patients and 50 healthy controls were determined by enzyme‐linked immunosorbent assays.ResultsA total of 135 proteins were identified in RA patients and the protein profile included 11 citrulline‐containing antigens. Three of the 11 citrullinated proteins had been reported in previous studies. ACPAs against the novel citrullinated epitopes from these proteins were increased in sera from the RA patients compared with those from healthy controls. Autoantibodies against one of the citrullinated antigens, lipopolysaccharide‐binding protein (LBP), was significantly increased in RA patients and associated with disease activities. The titer of anti‐citrullinated LBP antibodies (anti‐cLBP) was closely related to the infection incidence in RA patients.ConclusionSerum protein analysis by high‐precision proteomic technology is a feasible method to identify novel citrullinated epitopes in RA patients. Anti‐cLBP antibodies are associated with disease severity and infection in RA patients.

Association of HLA-G polymorphism and susceptibility to toxoplasmosis infection in rheumatoid arthritis patients.

Association of HLA-G polymorphism and susceptibility to toxoplasmosis infection in rheumatoid arthritis patients.

Acute surgical site infection after total knee arthroplasty in patients with rheumatoid arthritis versus osteoarthritis

Osteoarthritis is the main cause for total knee arthroplasty (TKA), followed by rheumatoid arthritis. Previous studies have reported conflicting results concerning the risk of surgical site infection after TKA for rheumatoid arthritis and osteoarthritis patients. Thus, this study aimed to examine whether rheumatoid arthritis patients had a higher risk of acute surgical site infection after TKA compared to osteoarthritis patients. We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database of the whole population from 2012 to 2015, and collected the medical records of osteoarthritis patients or rheumatoid arthritis patients who underwent TKA. To evaluate the risk of acute surgical site infection in rheumatoid arthritis patients, propensity score matching was implemented for osteoarthritis patients. Acute surgical site infection was observed in 2.58% of TKA cases in rheumatoid arthritis patients and 2.66% of TKA cases in osteoarthritis patients. Rheumatoid arthritis and osteoarthritis patients had comparable risk for 90-day (odds ratio = 0.81, 95% confidence interval: 0.371–1.768) and 1-year (odds ratio = 0.463, 95% confidence interval: 0.121–1.766) surgical site infection. In conclusion, patients with rheumatoid arthritis were not at higher risk of acute surgical site infection after TKA compared to osteoarthritis patients. The current treatment strategy for patients with RA is safe and appropriate if they require TKA.

The Incidence, Prevalence, and Associated Costs of Anemia, Malignancy, Venous Thromboembolism, Major Adverse Cardiovascular Events, and Infections in Rheumatoid Arthritis Patients by Treatment History in the United States.

ObjectiveComorbidities in rheumatoid arthritis (RA) can influence treatment selection, impact treatment persistency, and increase health care costs. This study assessed the magnitude of comorbidity burden via epidemiology (incidence and prevalence) and associated costs of select comorbidities in RA patients: anemia, malignancy, venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and infections, stratified by history of disease‐modifying antirheumatic drug (DMARD) exposure.MethodsFrom the IQVIA PharMetrics® Plus database, we selected adult patients with RA (2 or more RA diagnostic codes at least 30 days apart) at initiation of a new DMARD (DMARD‐naïve), after the first conventional synthetic DMARD (csDMARD) or after the first biologic DMARD (bDMARD). We assessed pre‐index prevalence (percentage) and on‐treatment incidence (per 100 patient‐years [P100PY]) of the aforementioned comorbidities. For patients with versus without incident conditions, we compared total all‐cause health care costs as unadjusted and adjusted for baseline characteristics and health care costs.ResultsPrior to initiating a new treatment, among DMARD‐naïve patients (N = 28,201), csDMARD switchers (N = 7,816), or bDMARD switchers (N = 4,656), the overall prevalence ranged from 14.1% to 16.2% (anemia), from 1.3% to 5.2% (malignancy, evaluated in csDMARD and bDMARD switchers), from 1.5% to 2.1% (VTE), from 1.8% to 2.9% (MACE), and from 66.6% to 76.1% (infections). Once on index treatment, overall incidence (P100PY) among the cohorts ranged from 6.9 to 8.9 (anemia), from 2.0 to 2.3 (malignancy), from 0.7 to 0.9 (VTE), from 1.6 to 2.0 (MACE), and from 77.4 to 87.7 (infections). The incident comorbidities (except herpes zoster) were associated with increased adjusted health care costs.ConclusionAnemia, malignancy, VTE, MACE, and infections affect patients with RA at all stages of their treatment journey and are associated with increased health care costs.

The risk of serious infection in rheumatoid arthritis patients receiving tocilizumab compared with tumor necrosis factor inhibitors in Korea

ObjectivesTo examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. MethodsWe conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. ResultsA total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90–1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02–1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49–0.87) compared to TNFi. ConclusionIn this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.

Severe HepatitisE virus infection in a patient with rheumatoid arthritis treated with baricitinib

Es wurde ein Patient mit rheumatoider Arthritis (RA) vorgestellt, der unter der Therapie mit dem Januskinase-1/2-Inhibitor Baricitinib eine Infektion mit dem Hepatitis-E-Virus (HEV) entwickelte. Unser Patient hatte bei seiner vierteljährlichen Routineuntersuchung deutlich erhöhte Transaminasen bei einer unauffälligen körperlichen Untersuchung. Es fanden sich Antikörper der IgM- und IgG-Klasse gegen HEV und ein erhöhtes C‑reaktives Protein (CRP) sowie HEV-RNA mittels Real-Time-PCR, was auf eine frische HEV-Infektion hinwies. Baricitinib wurde sofort abgesetzt. Die ausführliche Anamnese ergab, dass der Patient Tage vor der Konsultation Rindertartar verzehrt hatte, ohne dass gastrointestinale Symptome oder Fieber aufgetreten waren. Im weiteren Verlauf erholte sich der Patient vollständig, und die Leberfunktionstests und das CRP normalisierten sich innerhalb von 3 Monaten. Baricitinib wurde daraufhin wieder eingenommen. Bisher wurden nur wenige Daten zu HEV-Infektionen bei RA-Patienten, die mit JAK-Inhibitoren behandelt wurden, publiziert.

Immunoglobulin deficiencies in treated patients suffering from rheumatoid arthritis.

Immunoglobulins and antibodies to immunoglobulins (autoimmunoglobulins) have been identified to be implicated in the pathogenesis of rheumatoid arthritis (RA). Immunoglobulin deficiencies have been suggested to account for the increased risk of infections in RA patients. This study was carried out to determine the prevalence of immunoglobulin deficiencies in patients with RA and the identification of putative contributing factors. Immunoglobulin levels in blood samples of patients with rheumatoid arthritis were evaluated by an immunonephelometric assay. Demographic and disease related data (including age, sex, smoking habits, disease duration and activity, inflammatory markers) were assessed, and associations were identified by regression analysis. 539 patients were enrolled between 2011 and 2013. The most common immunoglobulin (Ig) deficiencies were those of IgM (24.5%) and IgG (19.9%). Most frequent deficiencies of subclasses were observed for IgG1 (42.3%), followed by IgG4 (10.4%), IgG2 (7.2%), and IgG3 (5.4%). Regression analyses revealed that deficiencies of IgM, IgG, IgG1, and IgG2 were more prevalent in older patients. In addition, smoking was associated with IgG2 deficiency, and IgA deficiency was associated with female sex. Occurrence of infections was significantly increased in patients with IgG, IgG2, and IgG4 deficiencies. RA patients displayed high rates of IgG and IgM deficiencies. In consequence, the assessment of immunoglobulin status should precede the application of immune modulating drugs to prevent a potential risk of infectious diseases. Prospective studies are needed to investigate the influence of immune modulating drugs on IgG and IgG subclass levels.

Nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in South Korea.

Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area.We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry.Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection.In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.

Screening of dental and sinus infections in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with increased risk of infections. Screening for oral (dental and/or sinus) infection could be proposed before biologic disease-modifying antirheumatic drugs (bDMARDs) initiation but is not systematically recommended. The aim of our study was to assess the prevalence of oral infection in RA patients requiring bDMARDs. This was a monocentric retrospective study. We included patients with RA and active disease requiring bDMARDs. Dental infection and sinusitis were assessed by a stomatologist and otorhinolaryngologist after clinical, panoramic dental X-ray and sinus CT evaluation. Factors associated with oral infections were analysed in uni- and multivariate models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). We included 223 RA patients (79.4% women, mean disease duration 8.9±8.6years). The mean age was 54.4±10.9years and mean Disease Activity Score in 28 joints 5.5±2.6. Systematic dental screening revealed infection requiring treatment before bDMARDs initiation in 46 (20.9%) patients. Sinusitis was diagnosed by the otorhinolaryngologist in 33 (14.8%) patients. Among the 223 patients, 69 (30.9%) had dental and/or sinus infection. On univariate analysis, active smoking was associated with increased probability of oral infection (OR=2.16 [95% CI 1.02-4.57], P=.038) and methotrexate with reduced probability (OR=0.43 [95% CI 0.23-0.81], P=.006). On multivariate analysis, no RA variables were associated with oral infection. In our study, asymptomatic oral infection was confirmed in one third of RA patients.

Comprehensive analysis of multiple cytokines and blood parameters for the diagnosis of bacterial infections in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are more susceptible to infections, which elevate the levels of relative cytokines. However, the ability of the cytokines levels to predicate bacterial infections in RA patients remains unclear. Here, we assessed the ability of the combination of serum cytokine levels and blood parameters to diagnose bacterial infections in RA patients. We measured the levels of a panel of serum cytokine and blood parameters in 168 RA patients and 81 healthy individuals. RA patients were divided into the bacterial infection (INFE) group (n = 76) and RA flare without INFE group (n = 92). Bacterial infection was confirmed by microbial culture, imaging, antibiotic response, and typical clinical symptoms. The discriminative ability of the combination of the cytokine levels and inflammatory parameters was assessed using the receiver-operating characteristic (ROC) curves analysis and a novel bioscore system. The levels of interleukin (IL)-6 (p = 0.006), IL-10 (p = 0.019), interferon (IFN)-γ (p = 0.033), CRP (p < 0.001), and ESR (p < 0.001) were higher in patients of the INFE group than in patients with RA flare, and the absolute numbers of CD19+ B cells (p < 0.001) and CD4+ T cells (p = 0.009) were lower. For discriminating bacterial infection, the combination of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, and CD4+ T cells, provided an area under the curve (AUC) of 0.827 [(95% confidence interval (CI): 0.760–0.881)], which was profoundly larger than that of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, or CD4+ T cells alone. In addition, we also developed a bioscore system based on the combination of these seven biomarkers. Seventeen (100%) patients with a bioscore of 0 were non-infected, while seven (100%) patients with a score of 7 had bacterial infections. The bioscore based on the combination of ESR, CRP, IL-6, IL-10, IFN-γ, CD19+ B cells and CD4+ T cells may be a promising and robust tool to diagnose bacterial infections in RA patients.