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Rheumatoid Arthritis in Sports

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Ovid: 5-Minute Sports Medicine Consult, The


Rheumatoid Arthritis in Sports
Kenneth Barnes
Shane Hudnall
Basics
Chronic systemic inflammatory autoimmune disorder that primarily affects the small joints of the body causing a symmetric polyarthritis
Description
  • Polyarthritis most commonly affecting the joints of the wrist, the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands, and the metatarsophalangeal (MTP) joints of the feet.
  • Less commonly affects cervical spine (though higher risk of atlantoaxial instability than general population), ankles, knees, hips, elbows, and shoulders
  • Extraarticular manifestations: Anemia, rheumatoid nodules (20–30%), pleuritis, pericarditis, entrapment neuropathies (carpal tunnel syndrome), episcleritis and scleritis (<1%), splenomegaly, renal disease, interstitial lung fibrosis, pericarditis, interstitial lung disease, vasculitis, Sjögren syndrome, Felty syndrome [rheumatoid arthritis (RA), splenomegaly, neutropenia]
Epidemiology
Incidence
  • Annual incidence roughly 3/10,000
  • Prevalence overall 1%; varies from 0.1–5% based on ethnic background
  • Predominant gender: Female > Male (2–5:1; increases in patients >60 yrs).
  • Mean age of onset is 52 yrs.
  • Peak age of onset is between 35 and 70 yrs, although possible in all ages.
Risk Factors
  • Female gender (pregnancy and oral contraceptive use may be protective)
  • Nulliparity
  • Family history (identical twins 3–4× more likely to share disease than fraternal twins)
  • HLA-DR4 (also tend to have more severe disease)
  • Cigarette smoking
  • Silica or asbestos exposure
  • Electrical workers
  • Wood workers
Etiology
  • RA is characterized by the presence of pannus (a proliferative mass of inflammatory vascularized tissue that may erode bone or cartilage).
  • Macrophages produce cytokines [eg, tissue necrosis factor α (TNF-α)], which produce many of the systemic features [eg, fatigue, weight loss, elevated C-reactive protein (CRP) and ESR, and joint damage].
Diagnosis
History
  • Clinical diagnosis: Usually symmetric synovitis (warmth, swelling, tenderness) of small joints (MCPs, PIPs, MTPs, wrists) with morning stiffness >1 hr that improves with activity
  • Progression to joint destruction and deformities (ulnar deviation at MCPs, volar subluxation at MCPs and wrists, swan-neck and/or boutonniere deformities of fingers)
  • Constitutional symptoms are very common (eg, low-grade fever, fatigue, myalgia, weight loss).
  • American Rheumatism Association (ARA) criteria (must have 4 of 7): Morning stiffness, symmetric arthritis, arthritis in 3+ joints, involvement of hand joints (all of these must have occurred >6 wks), rheumatoid nodules, serum rheumatoid factor positive, and/or radiographic changes
  • Note that ∼25% of patients have monarticular involvement at initial presentation.
  • Extraarticular manifestations (eg, chest pain, shortness of breath, skin changes, nodules, dry eyes or mouth)
Physical Exam
  • Examine joints thoroughly for synovitis (warmth, swelling, tenderness, erythema).
  • Look for deformities (swan-neck, boutonnieres, ulnar deviation of digits/wrists, volar subluxation at MCP or wrist).
  • Nail fold infarcts
  • Splinter hemorrhages
  • Rheumatoid nodules
  • Splenomegaly
  • Pericardial rub
  • Pleural effusions
Diagnostic Tests & Interpretation
Lab
  • Joint fluid exam most helpful: >10,000 WBCs with neutrophilic predominance characteristic but nondiagnostic
  • Rheumatoid factor positive >80% of the time but is not sufficient for diagnosis or to rule out diagnosis; if positive, more likely to have severe disease and extraarticular involvement than if was negative
  • Antinuclear antibodies (ANAs) also not diagnostic
  • ESR and CRP not specific but may be elevated
  • CBC: Anemia: Hemoglobin generally >9; level correlates with disease severity, leukocytosis, thrombocytosis.
  • Abnormal liver function tests: Low albumin: Directly linked to disease severity; elevated alkaline phosphatase
  • Anticyclic citrullinated peptide (anti-CCP) antibodies: Sensitivity of 67%, specificity of 95% for diagnosis of RA (1)
Imaging
  • X-rays: Erosions or bony decalcification in wrist or posteroanterior hand radiographs
  • Early: Obtain posteroanterior (PA) view of hands and wrists, anteroposterior (AP) view of both feet so that you have comparison for later bony destruction.
  • CT scan, MRI, and US much more sensitive for detecting early signs of damage and revealing erosions or edematous bony lesions. These studies may detect destruction earlier even in patients with normal findings on radiography (2,3).
Differential Diagnosis
  • Systemic lupus erythematosus (SLE)
  • Osteoarthritis (typically involves distal interphalangeals, knees, hips)
  • Reactive arthritis
  • Lyme disease
  • Gout
  • Pseudogout
  • Polymyalgia rheumatica
  • Hypothyroidism
  • Hypertrophic osteoarthropathy
  • Colitis
  • Ankylosing spondylitis
Treatment
  • Nonpharmacologic treatment: Patient education, relative rest, routine exercise, physical and occupational therapy, dietary therapy
  • Pharmacologic treatment:
    • Combination therapy is preferred and has shown greater efficacy than monotherapy.
    • Generally combine a nonbiologic DMARD with a biologic DMARD + burst of corticosteroids (intraarticular if single or few joints involved) for active disease, with continuation of DMARDs after flare is over (4).
    • Review specific side-effect profiles and monitoring parameters for the medications that are chosen.
Medication
  • Analgesia: NSAIDs helpful in controlling pain and inflammation, improving daily function, but they do not alter natural course of disease.
    • Consider COX-2 inhibitors in those who have GI side effects.
    • High-dose aspirin (12–16 tabs/day) or ibuprofen (2,400 mg/day)
  • DMARDs: Many of these agents inhibit progression of erosive disease; offer to all patients as early as possible in disease course; divided into nonbiologic and biologic agents (5).

    • P.515


  • Nonbiologic agents:
    • Methotrexate most commonly used nonbiologic agent and is generally preferred; takes effect as early as 4 wks; not to take in pregnancy; monitor for hematologic, hepatic, or pulmonary side effects (use folic acid supplementation 1 mg daily with methotrexate) (6).
    • Methotrexate
    • Sulfasalazine
    • Hydroxychloroquine
    • Minocycline
    • Azathioprine
    • Gold
  • Biologic agents:
    • Effective at modifying disease and preventing erosions but increased risk of infection
    • Tuberculosis skin test prior to initiation because can reactivate mycobacterial infections
    • As general rule, do not combine biologic agents with one another.
    • Etanercept: Inhibits action of TNF-α; SQ injection 50 mg every week or 25 mg twice weekly
    • Infliximab: Antibody to TNF-α; periodic IV infusion
    • Other biologic agents include adalimumab, rituximab, anakinra, abatacept, certolizumab, pegol, golimumab
  • Corticosteroids:
    • Oral, IV, and intra-articular forms
    • Prednisolone <7.5 mg/day is relatively safe; greater doses should be used only for short periods of time.
Additional Treatment
Referral
Consider total joint replacement for severe disability or pain that is unresponsive to medical therapy.
Ongoing Care
Patient Education
  • Exercise and increase in activity are associated with decreased level of pain, increased function, and better outcomes in patients with RA (best data shown for whole-body low-intensity group and individual exercise) (7).
  • Athletes with a history of cervical spine involvement need flexion/extension radiographs of C1 and C2 to assess risk of motion (atlantoaxial instability) and subsequent spinal cord injury.
  • Generally can play most sports, although contact sports and sports with a trampoline confer much greater risk and may be discouraged.
  • Athletes with ocular involvement should be screened by ophthalmologist before being allowed to play; may need eye protection.
  • If have systemic juvenile RA or HLA-B27-associated RA, must have cardiovascular assessment.
Prognosis
  • Clinical course and severity highly variable, ranging from insidious onset, slowly progressive disease with little destruction of joint spaces and few deformities (majority of cases), to a rapidly progressive disease leading to severe bony destruction and deformities (roughly 10–15%)
  • Poor prognostic factors:
    • Functional limitation
    • Extraarticular disease
    • Rheumatoid factor (RF) positivity or anti-CCP antibody positive
    • Bony erosions by x-ray
    • Cigarette smoking
Complications
  • 50% increased risk of cardiovascular disease death in those with RA (8)
  • Increased risk of stroke (especially ischemic) with RA (9)
  • 70% higher risk for developing infection (most likely related to immune dysfunction) (10)
  • Increased likelihood to develop lymphoma; correlates directly with RA disease severity (11)
References
1. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146:797–808.
2. Ostergaard M, et al. New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier. Arthritis Rheum. 2003;48:2128–2131.
3. Terslev L, et al. Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study. Arthritis Rheum. 2003;48:2434–2441.
4. Goekoop-Ruiterman YP, et al. Clinical and radiographic outcomes for four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381–3390.
5. Saag KG, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59:762–784.
6. Rantalaiho V, et al. The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial. Arthritis Rheum. 2009;60:1222–1231.
7. Ottawa Panel. Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercises in the management of rheumatoid arthritis in adults. Phys Ther. 2004;84:934–972.
8. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690–1697.
9. Nadareishvili Z, Michaud K, Hallenbeck JM, et al. Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study. Arthritis Rheum. 2008;59:1090–1096.
10. Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002;46:2287–2293.
11. Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165:2337–2344.
Additional Reading
Andreoli TE, Carpenter CCJ, Griggs RC, et al. Cecil essentials of medicine. 6th ed. 2004.
Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54:692–701.
Braunwald E, Fauci AS, Kasper DL, et al. Harrison's principles of internal medicine. 15th ed. 2001.
Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk In rheumatoid arthritis. Ann Rheum Dis. 2006.
Van der Heijde DM. Overview of radiologic efficacy of new treatments. Rheum Dis Clin North Am. 2004;30:285–293.
Codes
ICD9
  • 714.0 Rheumatoid arthritis
  • 714.30 Chronic or unspecified polyarticular juvenile rheumatoid arthritis
  • 714.31 Acute polyarticular juvenile rheumatoid arthritis
Clinical Pearls
RA can go into remission; must have 5+ to qualify for >2 mos: <15 min morning stiffness, no fatigue, no joint pain, no joint tenderness or pain with activity, no soft tissue swelling, ESR <30 in women or <20 in men.


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