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The perioperative use of which medication has been shown to increase the risk of post-operative infection following orthopaedic procedures in patients with rheumatoid arthritis (RA)?
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Of the medications listed, only entanercept has been shown to increase the risk of post-operative infection following orthopaedic procedures in patients with RA.
Entanercept is a TNF-alpha antagonist with a short half-life that is administered once or twice weekly in patients with RA. Since TNF-alpha plays a central role in the pathogenesis of RA and is instrumental in causing joint destruction, the inhibition of this molecule has shown excellent results in controlling disease. The most powered study on TNF-alpha inhibitor use in the perioperative period following an orthopaedic procedures demonstrated a significant increase in post-operative infection.
Howe et al. review the medical management of patients with RA who underwent orthopaedic procedures. They state that while there is conflicting information regarding TNF-alpha antagonists, they recommend holding them prior to major orthopaedic interventions.
Giles et al. review 91 patients with rheumatoid arthritis who underwent an orthopaedic procedure. They found TNF-alpha inhibitor therapy to be significantly associated with the development of a serious postoperative infection (p=.041)
Perhala et al. review 61 patients with RA who were treated with methotrexate during the perioperative period surrounding a total joint arthroplasty. They failed to find a significant increase in complications in this patient group, stating the perioperative use of methotrexate does not affect wound healing or increase the likelihood of periprosthetic infection.
Illustration A shows the site of action of TNA-alpha inhibitors in the RA pathway.
Answer 1: Naproxen should be discontinued 3 days prior to surgery because of its ability to increase bleeding time and the subsequent potential for increased blood loss.
Answer 2: Leflunomide is an inhibitor of pyrimidine synthesis. It has not been shown to increase the risk of post-operative infection.
Answer 3: Sulfasalazine's mechanism of action is largely unknown, but it has not been shown to increase the risk of post-operative infection.
Answer 5: Aspirin has not been shown to increase infection if continued in the perioperative period.
Howe CR, Gardner GC, Kadel NJ.
J Am Acad Orthop Surg. 2006 Sep;14(9):544-51. PMID: 16959892 (Link to Abstract)
Giles JT, Bartlett SJ, Gelber AC, Nanda S, Fontaine K, Ruffing V, Bathon JM
Arthritis Rheum.. 2006 Apr;55(2):333-7. PMID: 16583385 (Link to Abstract)
Perhala RS, Wilke WS, Clough JD, Segal AM.
Arthritis Rheum. 1991 Feb;34(2):146-52. PMID: 1994911 (Link to Abstract)
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Average 4.0 of 7 Ratings
Infliximab is a medication associated with opportunistic infections in patients with rheumatoid arthritis. What is the mechanism of action of Infliximab?
Inhibition of dihydrofolate reductase (DHFR)
Monoclonal antibody against CD20 on B-cell surface
Tumor necrosis factor inhibitor
Glucocorticoid receptor agonist
Infliximab is a tumor necrosis factor (TNF) inhibitor.
Infliximab was designed to modify the host immune response in rheumatoid arthritis (RA). It acts to neutralize both extracellular and membrane forms of TNF, a cytokine considered to be of major importance in the pathophysiology of RA. Complications with this medication include increased risk of opportunistic infection and dose-dependent increased risk of malignancies in patients with rheumatoid arthritis.
Bongartz et al. performed a meta-analysis of randomized trials reporting the harmful effects of anti-TNF therapy. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months.
Illustration A shows the biological properties and target cells of TNF.
Answer 1: This is the mechanism of action of Methotrexate.
Answer 2: This is the mechanism of action of Rituximab.
Answer 4: This is the mechanism of action of Cyclosporin.
Answer 5: This is the mechanism of action of Prednisone.
Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V
JAMA. 2006 May;295(19):2275-85. PMID: 16705109 (Link to Abstract)
Which of the following is more likely to occur following a total knee arthroplasty without patellar resurfacing versus a total knee arthroplasty with patellar resurfacing in patients with rheumatoid arthritis?
Native patellar dislocation
Anterior knee pain
Extensor tendon rupture
Decreased quadriceps strength
Patellar clunk syndrome
Patients with rheumatoid arthritis who undergo a total knee arthroplasty without patellar resurfacing are more likely to have anterior knee pain when compared to the same patient population with resurfaced patellas.
Resurfacing the patella during total knee arthroplasty is a topic of controversy. Those against resurfacing note minimal issues with patellar tilt and overstuffing the patellofemoral joint. Supporters of resurfacing state that the patellofemoral joint will eventually become arthritic if not resurfaced, and that the rate of anterior knee pain is much higher. Multiple studies, however, have shown superior results in patients with rheumatoid arthritis that have had their patella resurfaced.
Burnett et al. review the indications for patellar resurfacing during total knee arthroplasty. They consider not resurfacing the patella in patients less than 60 with non-inflammatory arthritis and a maintained patellofemoral joint space.
Holt et al. also review the role of patellar resurfacing. They mention that patellar resurfacing should be routinely done in patients with rheumatoid arthritis, preoperative patellofemoral pain, height greater than 160cm, weight greater than 60kg, or advanced patellar changes either pre- or intra-operatively.
Illustration A shows plain anteroposterior (a) and lateral (b) radiographs of the knee in a patient with rheumatoid arthritis. Degenerative changes are present in all 3 joint compartments. There is collapse of the lateral compartment with resultant valgus deformity. Erosion of the anterior aspect of the distal femoral metaphysis due to pannus is also seen.
Answer 1: Patellar dislocation has not been found to be higher in patellas that are not resurfaced.
Answer 3: Extensor tendon rupture is more common in patients that have had their patella resurfaced.
Answer 4: Multiple studies have not shown a difference in quadriceps strength with or without resurfacing.
Answer 5: Patellar clunk syndrome is more common in patients who have had their patella resurfaced.
Burnett RS, Bourne RB.
Instr Course Lect. 2004;53:167-86. PMID: 15116611 (Link to Abstract)
Holt GE, Dennis DA.
Clin Orthop Relat Res. 2003 Nov;(416):76-83. PMID: 14646743 (Link to Abstract)
Average 3.0 of 8 Ratings
A 64-year-old female with rheumatoid arthritis has decreased functional use of the left hand for activities of daily living. On physical examination she has fixed deformities of the metacarpophalangeal (MCP) joints as demonstrated in Figure A. A radiograph is shown in Figure B. Which of the following management options for the finger MCP joints most likely lead to the least amount of extensor lag and improvement of the ulnar drift at 1-year followup?
Tenosynovectomies with extensor indicis proprius (EIP) to EDQ transfer
Tenosynovectomies with extensor reconstructions (central slip imbrication, Fowler distal tenotomy)
Metacarpal joint resection arthroplasties with palmaris autograft interposition
Extensor tendon relocation, extrinsic tendon release, and metacarpophalangeal joint collateral ligament reefing
Metacarpophalangeal joint arthroplasties
The history, clinical image, and radiograph demonstrate severe MCP joint involvement with fixed deformities. MCP arthroplasty is the procedure of choice for severe finger MCP joint arthritis involvement or fixed deformities. Thumb MCP involvement is treated with arthrodesis in most cases.
Chung et al performed a Level 2 investigation of 81 patients with RA of the MCP finger joints that underwent silicone implant MCP arthroplasty. They found that both radial-sided and ulnar-sided fingers showed an improvement in ulnar drift from baseline to 1 year after surgery.
Kimball et al peformed a Level 5 review of MCP joint arthroplasty in RA patients. They state that patients can expect an arc of motion of 40 degrees to 60 degrees with improvement of finger extension and ulnar deviation.
Joyce presents Level 5 evidence discussing the various designs of MCP joint arthroplasty implants. Illustration A exhibits 3 different types of silicone MCP arthroplasty implants.
Illustration B demonstrates the postoperative appearance of the hand following MCP arthroplasty with correction of extension lag and ulnar drift.
Chung KC, Kotsis SV, Wilgis EF, Fox DA, Regan M, Kim HM, Burke FD
J Hand Surg Am. 2009 Nov;34(9):1647-52. PMID: 19896008 (Link to Abstract)
Kimball HL, Terrono AL, Feldon P, Zelouf DS.
Instr Course Lect. 2003;52:163-74. PMID: 12690846 (Link to Abstract)
Expert Rev Med Devices. 2004 Nov;1(2):193-204. PMID: 16293040 (Link to Abstract)
Average 3.0 of 13 Ratings
A 45-year-old woman with rheumatoid arthritis is being scheduled for a total knee athroplasty in 2 weeks. She is currently taking sulfasalazine, Penicillamine, and etanercept, a tumor necrosis factor inhibitor (aTNF-a). What changes should be made to her medication regimen prior to surgery?
Discontinuation of all three medications 4 weeks prior to surgery
Discontinuation of sulfasalazine 4 weeks prior to surgery, continuation of etanercept and penicillamine
Continuation of sulfasalazine, penicillamine, and etanercept
Continuation of sulfasalazine and penicillamine, discontinuation of etanercept 4 weeks prior to surgery
Continuation of penicillamine, discontinuation of sulfasalazine and etanercept 4 weeks prior to surgery
Anticytokine disease-modifying antirheumatic drugs (DMARD) have become increasingly popular in the treatment of RA. Immunosuppression and the risk of infection are potential complications for all anti-TNF-alpha medications. Current recommendations for cessation of immunosuppressive therapy are when the drug concentrations are at their lowest levels which include the following: 3 days after etanercept injection; 2 weeks prior to infliximab infusion; 10 days after adalimumab injection. Medications such as sulfasalazine and penicillamine may be continued during the pre and post-operative period. Recent evidence and guidelines such as those reviewed by Keith's paper, suggest that anti-TNF-alpha medications should be stopped 4 weeks prior to surgery.
Giles et al report in their case control series an increased infection rate of RA patients undergoing an orthopaedic procedure who were on TNF-a inhibitors as opposed to patients on more traditional treatment regimens like methotrexate and prednisone.
Am J. Orthop.. 2011 Dec;40(12):E272-5. PMID: 22268021 (Link to Abstract)
Average 3.0 of 25 Ratings
In the treatment of patients with rheumatoid arthritis, TNF-alpha is blocked by which of the following agents?
Etanercept is a biochemically designed soluble p75 tumor necrosis factor receptor immunoglobulin G fusion protein, which blocks the downstream effects of TNF.
Methotrexate is a chemotherapy agent used to inhibit lymphocytes. Gold inhibits monocytes, while sulfasalazine is an anti-inflammatory decreasing the production of prostaglandins and leukotrienes. Rituximab inhibits B-cells as it is a monoclonal antibody to CD20 antigen. Anakinra (Kineret) is a recombinant IL-1 receptor antagonist. Abatacept (Orencia) is a selective costimulation modulator that binds to CD-80 and CD-86 (inhibits T cells). Tocilizumab (Actemra)is an IL-6 receptor inhibitor (2nd line treatment for poor response to TNF-antagonist therapy).
Pisetsky wrote an editorial in NEJM discussing the development of TNF blockers through research, and the potential for the use of Etanercept in patients with juvenile RA through its inhibition of lymphotoxin-alpha.
N Engl J Med. 2000 Mar 16;342(11):810-1. PMID: 10717018 (Link to Abstract)
Average 2.0 of 18 Ratings
Which of the following medications when combined with methotrexate has been shown to be more effective than methotrexate alone in the treatment of rheumatoid arthritis?
Tetracycline was initially used in the treatment of rheumatoid arthritis (RA) because Mycoplasma was thought to be the causative agent. It was later found that tetracyclines have biologic effects on the inflammatory and immunologic cascade by inhibiting collagenase activity. Collagenase is an enzyme involved in breaking down macromolecules in the connective tissue, contributing to the pathologic changes of RA.
In a prospective study, O'Dell et al found that initial therapy with methotrexate plus doxycycline was superior to treatment with methotrexate alone. Furthermore, similar results for low-dose and high-dose doxycycline suggested that antimetalloproteinase effects were more important than the antibacterial effects.
O'Dell JR, Elliott JR, Mallek JA, Mikuls TR, Weaver CA, Glickstein S, Blakely KM, Hausch R, Leff RD.
Arthritis Rheum. 2006 Feb;54(2):621-7. PMID: 16447240 (Link to Abstract)
Average 3.0 of 27 Ratings
Which of the following drugs is an IL-1 antagonist typically used as a second line agent in the treatment of rheumatoid arthritis?
IL-1 receptor antagonist (IL-1Ra) is a naturally occurring molecule that blocks the biologic effects of the pro-inflammatory cytokine IL-1. A recombinant form of human IL-1Ra, anakinra, is used to manage rheumatoid arthritis patients who are refractory to more conventional forms of treatment. Methotrexate and leflunomide are DMARD's, and are typically prescribed if low dose corticosteroids are ineffective. Adalimumab and etanercept are both TNF-alpha blockers.
Kalliolias et al summarize clinical trials and meeting abstracts regarding the experience with anakinra in the treatment of patients with rheumatic diseases. They conlcude that anakinra is less effective than TNF-alpha blockers in the treatment of RA, and can be successful in treating adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis (previously known as juvenile rheumatoid arthritis, or JRA).
Kalliolias GD, Liossis SN.
Expert Opin Investig Drugs. 2008 Mar;17(3):349-59. PMID: 18321234 (Link to Abstract)
Average 1.0 of 62 Ratings
Vaughn-Jackson syndrome in rheumatoid arthritis is best described as?
Cranial migration of the dens from soft tissue erosion and bone loss between occiput and C1&C2
Rupture of flexor pollicis longus in the carpal tunnel
Synovitis in the DRUJ leading to supination of the carpal bones away from the head of the ulna
Rupture of the hand digital extensor tendons
Synovitis of the MTP joints with eventual hyperextension deformity of the MTP
Vaughn-Jackson syndrome describes the rupture of the hand digital extensor tendons, which start on the ulnar side of the wrist first and then move radially. This is thought to occur from DRUJ instability, resulting in dorsal prominence of the ulnar head, leading to an attritional rupture of the extensor tendons. Extensor digiti minimi is the extensor tendon commmonly ruptured.
Vaughn-Jackson first described the condition in his case report in JBJS in 1948.
Williamson et al. report on Vaughn-Jackson syndrome, and note that prevention is the best method of treatment of this finding. They note that consideration of the surrounding arthritic changes must be taken into account when treating chronic dorsal tendon attrition.
1) Cranial migration of dens from soft tissue erosion and bone loss between occiput and C1&C2 describes basilar invagination.
2) Rupture of flexor pollicis longus in the carpal tunnel describes Mannerfelt syndrome.
3) Synovitis in the DRUJ leading to supination of the carpal bones away from the head of the ulna describes Caput-ulna syndrome.
5) Synovitis of the MTP joints with eventual hyperextension deformity of the MTP is a common toe deformity seen with RA.
J Bone Joint Surg Br. 1948 Aug;30B(3):528-30. PMID: 18877990 (Link to Abstract)
Williamson SC, Feldon P.
Hand Clin. 1995 Aug;11(3):449-59. PMID: 7559823 (Link to Abstract)
Average 2.0 of 23 Ratings
Which immunoglobulin subtype does the rheumatoid factor target?
Rheumatoid factor does not target an immunoglobulin
Rheumatoid factor is an auto-antibody most commonly seen with rheumatoid arthritis. The presence of rheumatoid factor can also indicate generalized autoimmune activity unrelated to rheumatoid arthritis (e.g. tissue or organ rejection). Rheumatoid factor is itself an IgM antibody that is directed against the Fc portion of IgG antibody. Rheumatoid factor (IgM) attaches to IgG to form immune complexes which are deposited in tissues like the kidney and contribute to the overall disease process in rheumatoid arthritis.
James et al. assessed the occurrence and predictive factors for orthopaedic surgery in an cohort of patients with rheumatoid arthritis. Risk factors for surgery varied but the authors found that decreased inflammatory markers during the first year after diagnosis decreased the risk for subsequent surgery.
James D, Young A, Kulinskaya E, Knight E, Thompson W, Ollier W, Dixey J.
Rheumatology (Oxford). 2004 Mar;43(3):369-76. Epub 2004 Jan 13. PMID: 14722346 (Link to Abstract)
Average 4.0 of 20 Ratings
Which of the following biologic agents commonly used to treat rheumatoid arthritis (RA) DOES NOT target tumor necrosis factor-alpha (TNF-alpha)?
Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. Rituximab is used in combination with methotrexate to treat RA that has not responded to one or more types of treatment, including anti-tumor necrosis factor (TNF) blockers.
In rheumatoid arthritis, and other chronic inflammatory conditions, cytokines produced by activated T-cells/macrophages contribute to the pro-inflammatory state. TNF-alpha is thought to be one of the major cytokines involved in rheumatoid arthritis pathology. As a result, many biologic agents used to treat RA are directed towards blocking TNF-alpha or its receptors. These drugs are able to reduce inflammation and stop disease progression.
Elliot et al. evaluated the safety and efficacy of infliximab in 20 patients with active RA in an open phase I/II trial lasting 8 weeks. They found that treatment with anti-TNFa was safe, well tolerated and resulted in significant clinical and laboratory improvements.
Illustration A depicts five commonly used anti-TNF alpha biologic agents for the treatment of rheumatoid arhtirits with their usual dosing regimens.
Answer 1, 3-5: All of these biologic agents target TNF-alpha
Elliot MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katasikis P, Brennan FM, Bijl H, Ghrayeb J, Woody JN.
Arthritis Rheum. 2008 Feb;58(2 Suppl):S92-S101. PMID: 18240199 (Link to Abstract)
Average 2.0 of 15 Ratings
Medical treatment targeting TNF-alpha has revolutionized which of the following diseases?
Hunter syndrome (type II mucopolysaccharidosis)
Hereditary vitamin D resistant rickets
TNF-alpha medical therapy has revolutionized the treatment of rheumatoid arthritis.
DMARDs have revolutionized the treatment of rheumatoid arthritis, shifting the focus from treatment of symptoms to prevention of progression. Specific research into TNF-alpha modification has also shown progress in the treatment of juvenile rheumatoid arthritis, seronegative spondyloarthopathies, chronic recurrent multifocal osteomyelitis, and histiocytosis X. There are many different types and mechanisms of actions of DMARDs. One large family of medications (including etanercept) functions through antagonist action against TNF-alpha. Other types of DMARDs are anti-folate (methotrexate), IL-1 inhibitors (chloroquine), or pyrimidine synthesis inhibitors (leflunomide).
Howe et al. discusses how to modify TNF antagonists in the perioperative period. They recommend for minor procedures the medication can be continued. For moderate to intensive procedures, they recommend withholding etanercept for 1 week, and plan surgery for the end of the dosing interval for adalumimab and infliximab, and restart 10-14 days postoperatively.
Average 2.0 of 13 Ratings
A 43-year-old female with long-standing rheumatoid arthritis complains of right forefoot pain for several years. She has failed conservative treatment and radiographs are shown in Figure A. What is the most appropriate treatment?
Keller procedure with lesser metatarsal head resections
1st MTP joint fusion and lesser metatarsal head resections
1st MTP joint interposition arthroplasty and lesser MTP joint arthroplasties
Surgical treatment of a rheumatoid forefoot involves fusion of the 1st MTP and lesser metatarsal head resections. The earliest manifestation of rheumatoid arthritis of the forefoot is synovitis of the MTP joints with eventual hyperextension deformity of the MTP joints including distal migration of the forefoot pad, painful plantar callosities and skin ulcerations over bony prominences.
Coughlin et al reported on the results of reconstruction of the rheumatoid forefoot in the manner described above. In 58 feet with an average of 6 year follow-up, the patient satisfaction rating was excellent/good for 45, and pain was rated as absent or mild in 43 feet. Most patients still have some activity limitations.
Illustration A shows the preoperative and postoperative anteroposterior radiographs of hallux valgus deformity with lesser metatarsophalangeal joint erosions treated by 1st MTP joint fusion and lesser metatarsal head resections.
J Bone Joint Surg Am. 2000 Mar;82(3):322-41. PMID: 10724225 (Link to Abstract)
Average 3.0 of 14 Ratings
A 64-year-old woman with a longstanding history of rheumatoid arthritis complains of finger dysfunction for the past 6 months. Figure A displays her hand during active extension of all fingers. Figure B displays her hand maintaining her fingers extended following passive extension. What is the next most appropriate treatment for the ring finger?
Spiral oblique retinacular ligament reconstruction
Sagittal band reconstruction
Lateral band reconstruction
Central slip reconstruction
Triangular ligament and transverse retinacular ligament reconstruction
Sagittal band disruption is often associated with rheumatoid arthritis. When this patient attempts to actively extend the affected digit, the extensor tendon subluxates ulnarly as a result of the sagittal band rupture, and is left with an extensor lag. If one passively extends the finger fully, the patient is able to maintain this position, as the tendon is intact.
Sagittal band reconstruction can be performed with Watson's technique of creating a distally based tendon graft harvested from the central third of the extensor tendon, passed deep to the intermetacarpal ligament and sutured back to itself. Illustration A depicts an intraoperative view of the tendon before reconstruction and Illustration B displays tendon following sagittal band reconstruction. Illustration C displays all of the anatomic locations of the options listed above.
Average 4.0 of 28 Ratings