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Introduction
  • A chronic systemic autoimmune disease with a genetic predisposition
  • Epidemiology
    • incidence
      • most common form of inflammatory arthritis
    • demographics
      • affects 3% of women and 1% of men
  • Pathophysiology
    • immunology
      • cell-mediated (T cell-MHC type II) immune response against soft tissues (early), cartilage (later), and bone (later)
        • rheumatoid factor
          • an IgM antibody which recognizes and attacks native IgG antibodies
          • immune complex is then deposited in end tissues like the kidney as part of the pathophysiology 
        • mononuclear cells
          • are the primary cellular mediator of tissue destruction in RA
        • IL-1, TNF-alpha  
          • are part of cascade that leads to joint damage
        • immune response thought be related to
          • infectious etiology or
          • HLA locus
    • pathoanatomy
      • cascade of events includes
        • antigen-antibody and antibody-antibody reactions >
        • microvascular proliferation and obstruction >
        • synovial pannus formation (histology shows prominent intimal hyperplasia
        • joint subluxation, chondrocyte death/joint destruction, and deformity >
        • tendon tenosynovitis and rupture
  • Genetics
    • associated with specific HLA loci (HLA-DR4 & HLA DW4)
    • ~15% rate of concordance amongst monozygotic twins
  • Associated conditions
    • orthopaedic manifestations
      • see below
    • medical conditions & comorbidities
      • rheumatoid vasculitis
      • pericarditis
      • pulmonary disease
      • Felty's syndrome (RA with splenomegaly and leukopenia)
      • Still's disease (acute onset RA with fever, rash and splenomegaly)
      • Sjogren's syndrome (autoimmune condition affecting exocrine glands)
        • Decreased secretions from salivary and tear duct glands
        • Lymphoid tissue proliferation
  • Prognosis
    • significant advances in pharmacologic management have led to a decrease in surgical intervention
Presentation
  • Symptoms
    • insidious onset of morning stiffness and polyarthropathy
    • usually affects hands and feet
      • DIP joint of hand is usually spared
      • may also affect knees, cervical spine, elbows, ankle and shoulder
  • Physical exam
    • subcutaneous nodules in 20% (strong association with RF in serum)
    • ulnar deviation with metacarpophalangeal (MCP) subluxation, swan neck deformity
    • hallux valgus, claw toes, metatarsophlanageal (MTP) subluxation
    • joints become affected at later stage in disease process 
Imaging
  • Radiographs
    • periarticular erosions and osteopenia
    • protrusio acetabuli
      • medial migration of femoral head past the radiographic teardrop 
      • Also seen in Marfan's syndrome, Paget's disease, Otto's pelvis and other metabolic bone conditions 
    • joint space narrowing
Studies
  • Labs
    • anti-CCP (most sensitive and specific test)
    • elevated ESR
    • elevated CRP
    • positive RF titer (most commonly IgM)
      • targets the Fc portion of IgG
      • elevated in 75-80% of patients with RA
    • joint fluid testing
      • decreased complement
      • may have elevated RF levels
  • Diagnositic criteria
    • morning stiffness and swelling
    • subcutaneous nodules
    • positive laboratory tests
    • radiographic findings
Treatment
  • Nonoperative
    • pharmacologic treatment
      • indications
        • mainstay of treatment
      • medications (see table below)
        • first line of medications includes NSAIDS, antimalarials, remittent drugs (gold, sulfasalazine, methotrexate), steroids, cytotoxic drugs
        • more aggressive approach with DMARDs is now favored over pyramid approach 
      • outcomes
        • significant advances in pharmacologic management have significantly changes prognosis of disease
  • Operative
    • operative treatment dictated by specific condition
      • significant advances in pharmocologic management have led to a decrease in surgical intervention
    • important to obtain preoperative cervical spine radiographs
Pharmacologic Management of RA
1st Line: Low dose steroids
Corticosteroids  
2nd Line: Disease modifying anti-rheumatic drugs (DMARDs)
Methotrexate a folate analogue with anti-inflammatory properties linked to inhibition of neovascularization
therapeutic effects increased when combined with tetracyclines due to anti-collagenase properties
Leflunomide
an inhibitor of pyrimidine synthesis
Sulfasalazine exact mechanism unknown, but associated with a decrease in ESR and CRP
Hydroxychloroquine blocks the activation of toll-like receptors (TLR), which decreases the activity of dendritic cells, thus mitigating the inflammatory process
Others D-penicillamine
Biologic Agents: TNF antagonists
Etanercept (Enbrel) TNF-alpha receptor fusion protein (TNF type II receptor fused to IgG1: Fc portion) that binds to TNF-alpha   
Infliximab (Remicade) human mouse chimeric anti-TNF-alpha monoclonal antibody  
Adalimumab (Humira)
human anti-TNF-alpha monoclonal antibody
Golimumab (Simponi) human anti-TNF-alpha monoclonal antibody
Certolizumab (Cimzia) pegylated human anti-TNF-alpha monoclonal antibody
Biologic Agents: IL-1 antagonists
Anakinra (Kineret) recombinant IL1 receptor antogonist
Biologic Agents: Other
Rituximab (Rituxan) monoclonal antibody to CD20 antigen (inhibits B cells)
Abatacept (Orencia) selective costimulation modulator that binds to CD80 and CD86 (inhibits T cells)
Tocilizumab (Actemra) IL6 receptor inhibitor (2nd line treatment for poor response to TNF-antagonist therapy)
 
Cervical Spondylitis
  • Cervical spondylitis includes
    • atlantoaxial subluxation
    • basilar invagination
    • subaxial subluxation
Finger Conditions
  • Rheumatoid nodules
    • epidemiology
      • most common extra-articular manifestation of RA
      • seen in 25% of patients with RA and associated with aggressive disease
      • an extraarticular process found over IP joints, over olecranon, and over ulnar border of the forearm
    • prognosis
      • erosion through skin may lead to formation of sinus tract 
    • presentation
      • patients complain of pain and cosmetic concerns
    • treatment 
      • non operative
        • steroid injection
      • operative
        • surgical excision 
          • indications
            • cosmetic concerns, pain relief, diagnostic biopsy
  • Arthritis Mutilans
    • seen in patients with RA or psoriatic arthritis
    • digits develop gross instability with bone loss (pencil in cup deformity, wind chime fingers)
    • treated with interposition bone grafting and fusion
  • Ulnar drift at MCP joint
    • introduction
      • volar subluxation associated with ulnar drifting of digits
      • pathoanatomy
        • joint synovitits >
        • radial hood sagittal fiber stretching  >
          • concomitant volar plate stretching
        • extrinsic extensors subluxate ulnarly >
        • lax collateral ligaments allow ulnar deviation deformity > 
        • ulnar intrinsics contract further worsening the deformity > 
        • wrist radial deviation further worsens > 
        • flexor tendon eventually drifts ulnar
    • presentation
      • extensor lag at level of MCP joint
    • treatment
      • operative
        • synovectomyextensor tendon centralization, and intrinsic release 
          • indications
            • early disease
        • MCP arthroplasty
          • silicone MCP arthroplasty is most common
          • indications
            • late disease 
          • techniques
            • important to correct wrist deformity at same time if it is radially deviated
            • synovectomy, volar capsular resection, ulnar collateral ligament release, radial collateral ligament repair/reconstruction, extensor tendon realignment, intrinsic tendon release
          • outcomes
            • ultimate function is less predictable
            • overall patient satisfaction of 70%
            • 1 year followup shows improved ulnar drift and extensor lag
          • complications
            • infection
            • implant failure
            • deformity recurrence
  • Boutonneire deformity 
    • treat with PIP arthrodesis
  • Swan neck deformity  
    • treat with proximal Fowler tenotomy if PIP is supple or intrinsic release and MCP reconstruction if PIp flexion is limited
Thumb Conditions

Nalebuff Classification of Rheumatoid Thumb Deformities
Type
Description
Treatment
Type 1 Boutonniere Stage 1: Synovectomy with extensor hood reconstruction
Stage 2: MCP fusion or arthroplasty
Stage 3: IP and MCP fusion (if CMC is normal). IP fusion and MCP arthroplasty (if CMC is diseased)
Type 2 Boutonniere with CMC subluxation Same as Type 1 and 3
Type 3 Swan neck deformity Stage 1:splinting vs CMC arthroplasty
Stage 2: MCP fusion
Stage 3: MCP fusion with first web release
Type 4 Gamekeeper deformity Stage 1 (passively correctable): synovectomy, UCL reconstruction, and adductor fascia release
Stage 2 (fixed deformity) MP arthroplasty or fusion
Type 5 Swan neck with MPJ disease MP stabilized in flexion by volar capsulodesis
Type 6 Skeletal collapse (arthritis mutilans)
Combination of arthrodesis

Tendon Conditions
  • Extensor Tendon Rupture
    • epidemiology
      • frequency EDM > EDC (ring) > EDC (small) > EPL
    • treatment
      • tendon transfer, interposition graft, or Darrach's procedure
  • Sagittal band failure
    • pathoanatomy
      • extensor tendons migrate volar to center of rotation of MCP joint
    • physical exam
      • loose active extension, however if MCP placed in extension actively then patient can hold extended
    • treatment
      • sagittal band reconstruction (extensor hood reconstruction)
  • Mannerfelt syndrome
    • introduction
      • rupture of FPL (most common flexor rupture) in carpal tunnel due to scaphoid osteophytes
    • treatment
      • FDS to FPL tendon transfer
  • Vaughan-Jackson syndrome
    • introduction
      • describes the rupture of the hand digital extensor tendons which occur from the ulnar side of the wrist first then moves radially
    • pathoanatomy
      • results when DRUJ instability results in dorsal prominence of the ulnar head which results in an attritional rupture of the extensor tendons
        • EDM is the first extensor ruptured.
    • treatment
      • EIP to EDC transfer and distal ulna resection
Common Tendon Transfers in RA
Ruptured Tendon
Tendon Transfer
EPL EIP to EPL
EDM leave alone
EDM and EDC5 EIP to EDC5
EDM, EDC5, EDC4 EIP to EDM, EDC4 side to side to EDC3
 
Wrist Conditions
  • Caput-ulna syndrome
    • pathoanatomy
      • synovitis in the DRUJ > ECU subsheath stretching > ECU subluxation > supination of the carpal bones away from the head of the ulna > volar subluxation of the carpus away from the ulna > increased pressure over the extensor compartments > tendon rupture
      • be sure to distinguish from extensor lag caused by PIN compression neuropathy (seen in RA due to elbow synovitis)
    • treatment
      • distal ulna resection (Darrach) 
        • must also relocate ECU dorsally with a retinacular flap or perform ECU stabilization of ulna
      • Sauvé-Kapandji ulnar pseudoarthrosis
        • has advantage of preserving the TFCC
        • good option for younger patients
  • Radiocarpal Destruction
    • pathoanatomy
      • synovitis and capsular distension leads to supination, radial deviation, and ulnar and volar translocation of the carpus on the radius; this causes ulnar deviation of the fingers at the MP joints creating the classic zigzag deformity
    • treatment
      • synovectomy
        • indications
          • early disease
        • technique
          • transfer of ECRL to ECU to diminish deforming forces (Clayton's procedure)
      • radiolunate fusion (Chamay) 
        • indications
          • intermediate disease
      • wrist fusion
        • indications
          • advanced disease
          • remains gold standard
          • often combined with Darrach
      • total wrist arthroplasty
        • indications
          • is an option in some patients
          • advantages over fusion is motion and best in patients with reasonable motion preop
Elbow Conditions
  • Rheumatoid elbow
    • nonoperative
      • rheumatoid elbow is mainly managed with medical management and cortisone injections
    • operative
      • synovectomy and radial head excision
        • indications
          • focus of degeneration is in radiohumeral joint
          • posterior interosseous nerve compression secondary to radial head synovitis
        • technique
          • performed through lateral approach to elbow
      • interposition arthroplasy
        • indications
          • young active patients who are not candidates of TEA
        • technique
          • resection and contouring of humeral surface
          • cover humeral surface with cutis autograft, Achilles tendon, fascia, or dermal allograft
          • some use distraction external fixator to unload membrane and enhance its bonding to bone and improve motion
          • results less predictable than TEA, but avoids prosthetic complications
      • total elbow arthoplasty
        • indications
          • pain
          • loss of motion
          • instability
        • technique
          • semiconstrained device has best results
        • outcomes
          • reliable procedure for advanced RA of elbow
          • 5 lb single arm weight lifting restriction
Shoulder Conditions
  • Introduction
    • RA is most prevalent form of inflammatory process affecting the shoulder with >90% developing shoulder symptoms
    • commonly associated with rotator cuff tears
  • Evaluation
    • classic radiographic findings include
      • central glenoid wear
      • periarticular osteopenia
      • cysts
Hip Conditions
  • Protrusio acetabuli
Knee Conditions
  • Operative
    • synovectomy of knee
      • decreases pain and swelling but does not alter prevent radiographic progression and does not prevent the need for TKA in the future
      • normal synovium reforms, but degenerates to rheumatoid synovium over time
      • range of motion is not improved
    • total knee arthroplasty
      • rheumatoid arthritis is considered an indication for resurfacing of the patella during total knee arthroplasty
Foot & Toe Conditions
  • Introduction
    • usually bilateral and symmetric
    • forefoot joints are the first to be affected
    • human leukocyte antigen (HLA)-DR4 positive
  • Toe hyperextension deformity
    • 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.
    • treatment
      • arthrodesis of the 1st MTP joint and lesser MTP joint resections
  • Talonavicular arthritis
    • common to have degenerative changes
    • treat with fusion
Complications
  • Postoperative infection
    • history of prior surgical site infection (SSI)
      • is the most significant risk factor for development of another SSI
    • immunosuppressive therapy
      • the literature is controversial whether RA patients on immunosuppressive therapy have significantly increased infection rates for orthopaedic procedures
      • pharmacologic therapy may need to be changed prior to surgical interventions
        • surgery should be performed when immunosuppressive agents are at their lowest levels
          • etanercept should be discontinued 3 days prior to surgical procedures
          • adalimumab should be discontinued 10 days prior to surgery
          • the lowest level of infliximab is found 2 weeks prior to the next scheduled infusion
 

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Questions (14)

(OBQ13.59) 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)? Review Topic

QID:4694
1

Naproxen

1%

(15/2162)

2

Leflunomide

3%

(75/2162)

3

Sulfasalazine

6%

(135/2162)

4

Entanercept

89%

(1914/2162)

5

Aspirin

1%

(13/2162)

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

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.

Incorrect Answers:
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.

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(OBQ13.254) Infliximab is a medication associated with opportunistic infections in patients with rheumatoid arthritis. What is the mechanism of action of Infliximab? Review Topic

QID:4889
1

Inhibition of dihydrofolate reductase (DHFR)

2%

(39/1767)

2

Monoclonal antibody against CD20 on B-cell surface

26%

(452/1767)

3

Tumor necrosis factor inhibitor

70%

(1245/1767)

4

Calcineurin inhibitor

0%

(5/1767)

5

Glucocorticoid receptor agonist

1%

(10/1767)

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PREFERRED RESPONSE 3

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.

Incorrect Answers:
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.

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(OBQ12.137) 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? Review Topic

QID:4497
1

Native patellar dislocation

4%

(111/2661)

2

Anterior knee pain

82%

(2170/2661)

3

Extensor tendon rupture

4%

(94/2661)

4

Decreased quadriceps strength

2%

(56/2661)

5

Patellar clunk syndrome

8%

(212/2661)

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PREFERRED RESPONSE 2

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.

Incorrect Answers:
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.

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(OBQ11.190) 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? Review Topic

QID:3613
FIGURES:
1

Tenosynovectomies with extensor indicis proprius (EIP) to EDQ transfer

2%

(25/1614)

2

Tenosynovectomies with extensor reconstructions (central slip imbrication, Fowler distal tenotomy)

9%

(152/1614)

3

Metacarpal joint resection arthroplasties with palmaris autograft interposition

5%

(75/1614)

4

Extensor tendon relocation, extrinsic tendon release, and metacarpophalangeal joint collateral ligament reefing

21%

(341/1614)

5

Metacarpophalangeal joint arthroplasties

62%

(1007/1614)

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PREFERRED RESPONSE 5

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.

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(OBQ10.4) 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? Review Topic

QID:3092
1

Discontinuation of all three medications 4 weeks prior to surgery

10%

(163/1616)

2

Discontinuation of sulfasalazine 4 weeks prior to surgery, continuation of etanercept and penicillamine

5%

(78/1616)

3

Continuation of sulfasalazine, penicillamine, and etanercept

5%

(76/1616)

4

Continuation of sulfasalazine and penicillamine, discontinuation of etanercept 4 weeks prior to surgery

63%

(1024/1616)

5

Continuation of penicillamine, discontinuation of sulfasalazine and etanercept 4 weeks prior to surgery

17%

(267/1616)

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PREFERRED RESPONSE 4

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.


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(OBQ10.83) In the treatment of patients with rheumatoid arthritis, TNF-alpha is blocked by which of the following agents? Review Topic

QID:3171
1

Tocilizumab

2%

(30/1580)

2

Anakinra

3%

(40/1580)

3

Etanercept

88%

(1388/1580)

4

Abatacept

1%

(15/1580)

5

Rituximab

7%

(104/1580)

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PREFERRED RESPONSE 3

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.


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(OBQ10.93) 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? Review Topic

QID:3181
1

Nitrofurantoin

6%

(105/1712)

2

Rifampin

21%

(362/1712)

3

Azithromycin

4%

(68/1712)

4

Erythromycin

9%

(157/1712)

5

Doxycycline

59%

(1014/1712)

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PREFERRED RESPONSE 5

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.


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(OBQ10.263) Which of the following drugs is an IL-1 antagonist typically used as a second line agent in the treatment of rheumatoid arthritis? Review Topic

QID:3314
1

Anakinra

47%

(934/1968)

2

Methotrexate

8%

(165/1968)

3

Leflunomide

5%

(105/1968)

4

Adalimumab

14%

(268/1968)

5

Etanercept

25%

(489/1968)

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PREFERRED RESPONSE 1

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).


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(OBQ09.162) Vaughn-Jackson syndrome in rheumatoid arthritis is best described as? Review Topic

QID:2975
1

Cranial migration of the dens from soft tissue erosion and bone loss between occiput and C1&C2

7%

(53/808)

2

Rupture of flexor pollicis longus in the carpal tunnel

4%

(35/808)

3

Synovitis in the DRUJ leading to supination of the carpal bones away from the head of the ulna

9%

(76/808)

4

Rupture of the hand digital extensor tendons

76%

(617/808)

5

Synovitis of the MTP joints with eventual hyperextension deformity of the MTP

3%

(23/808)

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PREFERRED RESPONSE 4

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.

Incorrect Answers:
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.


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(OBQ09.179) Which immunoglobulin subtype does the rheumatoid factor target? Review Topic

QID:2992
1

IgA

3%

(33/1205)

2

IgE

2%

(19/1205)

3

IgM

24%

(285/1205)

4

IgG

61%

(732/1205)

5

Rheumatoid factor does not target an immunoglobulin

11%

(134/1205)

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PREFERRED RESPONSE 4

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.


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(OBQ09.274) Which of the following biologic agents commonly used to treat rheumatoid arthritis (RA) DOES NOT target tumor necrosis factor-alpha (TNF-alpha)? Review Topic

QID:3087
1

Infliximab

4%

(8/224)

2

Rituximab

75%

(167/224)

3

Etanercept

11%

(24/224)

4

Golimumab

4%

(9/224)

5

Adalimumab

6%

(14/224)

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PREFERRED RESPONSE 2

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.

Incorrect Answers:
Answer 1, 3-5: All of these biologic agents target TNF-alpha

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(OBQ05.128) Medical treatment targeting TNF-alpha has revolutionized which of the following diseases? Review Topic

QID:1014
1

Osteoarthritis

2%

(3/166)

2

Rheumatoid arthritis

96%

(160/166)

3

Hunter syndrome (type II mucopolysaccharidosis)

1%

(1/166)

4

Hereditary vitamin D resistant rickets

1%

(1/166)

5

Gout

0%

(0/166)

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PREFERRED RESPONSE 2

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.


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(OBQ05.143) 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? Review Topic

QID:1029
FIGURES:
1

Bunionectomy

1%

(10/841)

2

Keller procedure with lesser metatarsal head resections

7%

(56/841)

3

1st MTP joint fusion and lesser metatarsal head resections

85%

(711/841)

4

Forefoot amputation

1%

(7/841)

5

1st MTP joint interposition arthroplasty and lesser MTP joint arthroplasties

7%

(57/841)

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PREFERRED RESPONSE 3

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.

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(OBQ05.151) 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? Review Topic

QID:1037
FIGURES:
1

Spiral oblique retinacular ligament reconstruction

4%

(38/973)

2

Sagittal band reconstruction

65%

(629/973)

3

Lateral band reconstruction

8%

(82/973)

4

Central slip reconstruction

16%

(157/973)

5

Triangular ligament and transverse retinacular ligament reconstruction

7%

(65/973)

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PREFERRED RESPONSE 2

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.

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