Susan M. Goodman

Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis

CD4+ T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1hiCXCR5−CD4+ T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1hiCXCR5− ‘peripheral helper’ T (TPH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hiCXCR5+ T follicular helper cells, TPH cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between TPH cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in TPH cells. TPH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.

Perioperative Management of Medications Used in the Treatment of Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA), an inflammatory arthritis that can destroy joint structures, are often on multiple medications to control disease activity. These medications may have significant toxicities and side effects. Over the course of their lifetime, patients with this disease often require orthopedic procedures, including total joint arthroplasty, and the medications they are taking present management issues specific to the perioperative period. As many of these medications are immunosuppressive, the concern for postoperative infection and delayed wound healing are particularly worrisome. We conducted a review of the available literature pertaining to the perioperative use of the most commonly prescribed medications for RA. Although the existing data directly addressing perioperative complications in orthopedic surgery is sparse, information on relevant complications resulting from the general use of these drugs may be used as a basis for conservative recommendations.

US Trends in Rates of Arthroplasty for Inflammatory Arthritis Including Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, and Spondyloarthritis

Although rates of arthroplasty have increased dramatically, rates among patients with rheumatoid arthritis (RA) are reported to be decreasing. It is not known if this is also the case among patients with other inflammatory arthritides. This study was undertaken to evaluate rates of arthroplasty due to RA, juvenile idiopathic arthritis (JIA), spondyloarthritis (SpA), and a composite group of patients with inflammatory arthritides (IA), compared to arthroplasty rates among patients without inflammatory or autoimmune conditions.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA).

Patterns and Associated Risk of Perioperative Use of Anti-Tumor Necrosis Factor in Patients with Rheumatoid Arthritis Undergoing Total Knee Replacement

Objective. The patterns and risks of perioperative use of anti-tumor necrosis factor (anti-TNF) medication in patients with rheumatoid arthritis (RA) are not well studied. We examined the patterns of perioperative anti-TNF use and risk of postoperative adverse events (AE) in patients undergoing total knee replacement (TKR). Method. Retrospective cohort study with followup. RA cases within a TKR registry were identified by ICD-9 code (714.0) or self-report. Mailed questionnaires queried anti-TNF use and duration of RA. AE were determined by chart review and patient self-report, and included surgical site infection, pulmonary embolus, deep venous thrombosis, pneumonia, and any infection or re-operation within 6 months. Results. There were 268 TKR cases with RA. The stop time for anti-TNF preoperatively correlated with dosing schedule; restart time was after wound healing. There were 7 surgical site infections (3%), one (0.4%) of which was a deep joint infection in bilateral TKA requiring explant. The anti-TNF group had 3.26% (3/92) local site infection versus 2.10% (3/143) in the group without anti-TNF and this difference was not statistically significant (Fisher exact test, p = 0.68). The one deep joint infection was in the anti-TNF group. Six-month AE rate was 7.61% in the anti-TNF group versus 6.99% in the group without anti-TNF (Fisher exact test, p = 1.0). Conclusion. There was a low risk of infection and perioperative adverse events in patients with RA receiving anti-TNF therapy who were undergoing TKR. This raises the question whether it is necessary to stop anti-TNF for a long period prior to surgery. Given the possible risks associated with stopping anti-TNF, including worsening of disease, further study is needed to determine optimal perioperative use of anti-TNF among patients with RA undergoing TKR.

Rheumatoid arthritis: Perioperative management of biologics and DMARDs

OBJECTIVE Arthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares. METHODS Published literature regarding arthroplasty in RA has been reviewed and discussed. RESULTS Some DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined. CONCLUSION This article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.

Rheumatoid Arthritis vs Osteoarthritis in Patients Receiving Total Knee Arthroplasty: Perioperative Outcomes

There is a paucity of data available on perioperative outcomes of patients undergoing total knee arthroplasty (TKA) for rheumatoid arthritis (RA). We determined differences in demographics and risk for perioperative adverse events between patients suffering from osteoarthritis (OA) versus RA using a population-based approach. Of 351,103 entries for patients who underwent TKA, 3.4% had a diagnosis of RA. RA patients were on average younger [RA: 64.3 years vs OA: 66.6 years; P<0.001] and more likely female [RA: 79.2% vs OA: 63.2%; P<0. 001]. The unadjusted rates of mortality and most major perioperative adverse events were similar in both groups, with the exception of infection [RA: 4.5% vs. OA: 3.8%; P<0.001]. RA was not associated with increased adjusted odds for combined adverse events.

Patients with Rheumatoid Arthritis Are More Likely to Have Pain and Poor Function After Total Hip Replacements than Patients with Osteoarthritis

Objective. Total hip replacement (THR) outcomes have been worse for patients with rheumatoid arthritis (RA) compared with those who have osteoarthritis (OA). Whether this remains true in contemporary patients with RA with a high use of disease-modifying and biologic therapy is unknown. The purpose of our study is to assess pain, function, and quality of life 2 years after primary THR, comparing patients with RA and patients with OA. Methods. Baseline and 2-year data were compared between validated patients with RA and patients with OA who were enrolled in a single-center THR registry between May 1, 2007, and February 25, 2011. Results. There were 5666 eligible primary THR identified, of which 193 were for RA. RA THR had worse baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (44.8 vs 53.2, p < 0.001) and function (38.7 vs 49.9, p < 0.001) compared with OA. These differences remained after surgery: pain (88.4 vs 94.0, p < 0.001) and function (82.9 vs 91.8, p < 0.001). Patients with RA were as likely to have a significant improvement as patients with OA (Δ WOMAC > 10) in pain (94% vs 96%, p = 0.35) and function (95% vs 94%, p = 0.69), but were 4 times as likely to have worse function (WOMAC ≤ 60; 19% vs 4%, p < 0.001) and pain (12% vs 3%, p < 0.001). In multivariate logistic regression controlling for multiple potential confounders, RA increased the odds of poor postoperative function (OR 4.32, 95% CI 1.57–11.9), and in patients without a previous primary THR, worse postoperative pain (OR 3.17, 95% CI 1.06–9.53). Conclusion. Contemporary patients with RA have significant improvements in pain and function after THR, but higher proportions have worse 2-year pain and function. In addition, RA is an independent predictor of 2-year pain and poor function after THR, despite high use of disease-modifying therapy.

Arthroplasty Rates Are Increased Among US Patients with Systemic Lupus Erythematosus: 1991–2005

Objective. To evaluate population-based systemic lupus erythematosus (SLE) arthroplasty rates and compare them with rates in patients with no inflammatory or autoimmune conditions. Methods. Administrative hospital discharge databases from 10 American states were used to compare knee, hip, and shoulder arthroplasty rates from 1991 to 2005 in patients with SLE and in patients with no inflammatory or autoimmune conditions. Results. Arthroplasties were performed on patients with SLE (n = 4253) and patients with noninflammatory conditions (n = 2,762,660). Arthroplasty rates for patients with noninflammatory conditions almost doubled from 1991 to 2005 (124.5 cases/100,000 persons vs 247.5/100,000; p < 0.001). A similar trend was observed for SLE (0.17/100,000 vs 0.38/100,000; p < 0.001). The mean age at arthroplasty in patients with noninflammatory conditions decreased (71.5 ± 11.8 vs 69.0 ± 12.0; p < 0.001), whereas the mean age in patients with SLE increased (47.3 ± 17.0 vs 56.8 ± 16.0; p < 0.001). When stratified by age and sex, arthroplasty in cases of SLE increased in all groups except for women < 44 years old. In 1991, osteonecrosis accounted for 53% and osteoarthritis (OA) 23% of cases of SLE; by 2005 this relationship had reversed, with osteonecrosis accounting for 24% and OA 61% of cases of SLE. Conclusion. From 1991 to 2005, arthroplasty rates increased in patients with SLE in similar proportions to overall joint replacement rates. The age of patients with SLE arthroplasty increased and fewer cases were due to osteonecrosis. These data suggest significant changes are occurring — patients with SLE are now living long enough to develop OA and are healthy enough to undergo elective surgery.

Lower extremity arthroplasty in patients with inflammatory arthritis: preoperative and perioperative management.

&NA; Spondylarthritis, which includes conditions such as ankylosing spondylitis and psoriatic arthritis, and rheumatoid arthritis are the most common forms of inflammatory arthritis. Joint inflammation and damage may result in the need for arthroplasty, and the surgeon must be aware of the perioperative challenges associated with these systemic diseases. In patients with inflammatory arthritis who have polyarticular disease and spinal involvement at the time of presentation for lower extremity arthroplasty, preoperative evaluation must include careful evaluation of all joints, including the cervical spine. Preoperative assessment and perioperative management must be appropriate to minimize cardiac and pulmonary complications. Finally, the perioperative management of medications used to manage inflammatory arthritis is critical because these medications may increase the risk of infection and compromise wound healing.