Rheumatoid Arthritis

Topic updated on 02/10/16 7:12am
  • 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
  • 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 
  • 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
  • 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
  • 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
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
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 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
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
  • 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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Qbank (19 Questions)

(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)? Topic Review Topic

1. Naproxen
2. Leflunomide
3. Sulfasalazine
4. Entanercept
5. Aspirin

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

1. Inhibition of dihydrofolate reductase (DHFR)
2. Monoclonal antibody against CD20 on B-cell surface
3. Tumor necrosis factor inhibitor
4. Calcineurin inhibitor
5. Glucocorticoid receptor agonist

(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? Topic Review Topic

1. Native patellar dislocation
2. Anterior knee pain
3. Extensor tendon rupture
4. Decreased quadriceps strength
5. Patellar clunk syndrome

(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? Topic Review Topic
FIGURES: A   B        

1. Tenosynovectomies with extensor indicis proprius (EIP) to EDQ transfer
2. Tenosynovectomies with extensor reconstructions (central slip imbrication, Fowler distal tenotomy)
3. Metacarpal joint resection arthroplasties with palmaris autograft interposition
4. Extensor tendon relocation, extrinsic tendon release, and metacarpophalangeal joint collateral ligament reefing
5. Metacarpophalangeal joint arthroplasties

(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? Topic Review Topic

1. Discontinuation of all three medications 4 weeks prior to surgery
2. Discontinuation of sulfasalazine 4 weeks prior to surgery, continuation of etanercept and penicillamine
3. Continuation of sulfasalazine, penicillamine, and etanercept
4. Continuation of sulfasalazine and penicillamine, discontinuation of etanercept 4 weeks prior to surgery
5. Continuation of penicillamine, discontinuation of sulfasalazine and etanercept 4 weeks prior to surgery

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

1. Tocilizumab
2. Anakinra
3. Etanercept
4. Abatacept
5. Rituximab

(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? Topic Review Topic

1. Nitrofurantoin
2. Rifampin
3. Azithromycin
4. Erythromycin
5. Doxycycline

(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? Topic Review Topic

1. Anakinra
2. Methotrexate
3. Leflunomide
4. Adalimumab
5. Etanercept

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

1. Cranial migration of the dens from soft tissue erosion and bone loss between occiput and C1&C2
2. Rupture of flexor pollicis longus in the carpal tunnel
3. Synovitis in the DRUJ leading to supination of the carpal bones away from the head of the ulna
4. Rupture of the hand digital extensor tendons
5. Synovitis of the MTP joints with eventual hyperextension deformity of the MTP

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

1. IgA
2. IgE
3. IgM
4. IgG
5. Rheumatoid factor does not target an immunoglobulin

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

1. Infliximab
2. Rituximab
3. Etanercept
4. Golimumab
5. Adalimumab

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

1. Osteoarthritis
2. Rheumatoid arthritis
3. Hunter syndrome (type II mucopolysaccharidosis)
4. Hereditary vitamin D resistant rickets
5. Gout

(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? Topic Review Topic
FIGURES: A          

1. Bunionectomy
2. Keller procedure with lesser metatarsal head resections
3. 1st MTP joint fusion and lesser metatarsal head resections
4. Forefoot amputation
5. 1st MTP joint interposition arthroplasty and lesser MTP joint arthroplasties

(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? Topic Review Topic
FIGURES: A   B        

1. Spiral oblique retinacular ligament reconstruction
2. Sagittal band reconstruction
3. Lateral band reconstruction
4. Central slip reconstruction
5. Triangular ligament and transverse retinacular ligament reconstruction

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