II. Epidemiology

  1. Prevalence: 0.3 - 1.5% of population
  2. Women affected 2-3x more often
  3. Twin concordance: 30 to 50%
  4. Peak Incidence ages 30 to 50 years
  5. Associated with HLA-DR4 and HLA-DR1 haplotypes
  6. Associated with STAT4 gene and CD40 locus

III. Pathophysiology: Order of changes

  1. Synovial Macrophage and fibroblast activation
  2. Cytokine production (interleukin-6, tumor necrosis factor or TNF)
  3. Lymphoctes infiltrate perivascular areas
  4. Synovial thickening (Pannus formation and spread)
  5. Neovascularization
  6. Local micro-Vasculitis
  7. Chondrocyte, Osteoclast, CD4+ Helper activity
  8. Endothelial proliferation
  9. Joint space narrowing
  10. Cytokine release (resulting in fever, Anemia)

IV. Risk Factors

  1. Increased risk
    1. Female gender
    2. Family History of Rheumatoid Arthritis
    3. Tobacco abuse (most significant environmental trigger)
      1. Relative Risk: 2.2 for more than 40 pack year smokers
    4. More than 3 cups coffee daily (esp. decaffeinated)
  2. Decreased risk
    1. Women who've had children
    2. Breastfeeding
  3. References
    1. Kuder (2002) Rev Environ Health 17:307-15 [PubMed]
    2. [PubMed]

V. Course

  1. Self-limited (5-20%)
  2. Minimally progressive (5-20%)
  3. Progressive (60-90%)
    1. Early damage
      1. Two Years from onset:
        1. Joint space narrowing and erosions in 50%
      2. Ten years from onset:
        1. Young working patients are disabled: 50%
    2. Early death by multiple causes
      1. Women's Life Expectancy reduced by 10 years
      2. Men's Life Expectancy reduced by 4 years

VIII. Labs (ARA recommended, but do not exclude diagnosis)

  1. Initial Labs
    1. Complete Blood Count with differential
    2. Rheumatoid Factor (Initially positive in 70%)
    3. Sedimentation Rate (ESR) or C-Reactive Protein (C-RP)
    4. Consider Anticyclic citrullinated peptide Antibody
    5. Consider Antinuclear Antibody (especially in juvenile forms as has prognostic value)
  2. Additional labs in preparation for rheumatic agents
    1. Liver Function Tests
    2. Renal Function tests
  3. Labs needed before Steroids, TNF Inhibitors or DMARDs
    1. PPD with candida controls
    2. HBsAg
    3. Hepatitis C Antibody
  4. Markers of disease course
    1. C-Reactive Protein (C-RP)
    2. Erythrocyte Sedimentation Rate
    3. Wrist XRay or Ankle XRay
    4. Anticyclic citrullinated peptide Antibody

IX. Imaging

  1. Obtain baseline hand and feet XRays
    1. May demonstrate periarticular erosive changes
    2. May define more aggressive disease
  2. See Rheumatoid Arthritis Related XRay Changes
  3. Chest XRay (erosions define moderate to severe disease)

XI. Associated Conditions

  1. See Rheumatoid Arthritis Extra-articular Signs
  2. Atlanto-axial instability
    1. Exercise caution with intubation
    2. Risk of C-Spine Fracture with Trauma
  3. Lymphoma
  4. Insulin Resistance (50-60%)
  5. Coronary Artery Disease
    1. See Cardiac Risk Management
    2. Rheumatoid Arthritis is now considered a coronary equivalent (similar to Diabetes Mellitus cardiovascular risk)
      1. Kaplan (2006) Curr Opin Rheumatol 18:289–97 [PubMed]
    3. Methotrexate is associated with reduced cardiovascular risk
      1. Westlake (2010) Rheumatology 49: 295-307 [PubMed]

XII. Prognosis: Predictors of prolonged Remission (achieved in 10-50% of patients)

  1. Males
  2. Non-smokers
  3. Age under 40 years old
  4. Onset after age 65 years
  5. Shorter duration of Rheumatoid Arthritis
  6. Milder Rheumatoid Arthritis disease course
  7. Acute phase reactants not elevated (e.g. C-RP)
  8. Rheumatoid Factor negative
  9. Anti-citrullinated protein Antibody negative

XIII. Prognosis: Poor Prognostic Signs

  1. Hyper-acute onset (overnight onset)
  2. Multiple joint involvement (especially >20 joints)
  3. High titer Rheumatoid Factor (RF)
  4. HLA-DRBI 0404
  5. Low dose Corticosteroid resistance
  6. Early loss of function or young age of onset
  7. Higher Erythrocyte Sedimentation Rate
  8. Rheumatoid Arthritis Extra-articular Signs

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Ontology: Rheumatoid Arthritis (C0003873)

Definition (MEDLINEPLUS)

Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in your joints. It can affect any joint but is common in the wrist and fingers.

More women than men get rheumatoid arthritis. It often starts in middle age and is most common in older people. But children and young adults can also get it. You might have the disease for only a short time, or symptoms might come and go. The severe form can last a lifetime.

Rheumatoid arthritis is different from osteoarthritis, the common arthritis that often comes with older age. RA can affect body parts besides joints, such as your eyes, mouth and lungs. RA is an autoimmune disease, which means the arthritis results from your immune system attacking your body's own tissues.

No one knows what causes rheumatoid arthritis. Genes, environment and hormones might contribute. Treatments include medicine, lifestyle changes and surgery. These can slow or stop joint damage and reduce pain and swelling.

NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Definition (NCI_NCI-GLOSS) An autoimmune disease that causes pain, swelling, and stiffness in the joints, and may cause severe joint damage, loss of function, and disability. The disease may last from months to a lifetime, and symptoms may improve and worsen over time.
Definition (NCI) A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Definition (MSH) A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Definition (CSP) chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures; etiology is unknown, but autoimmune mechanisms have been implicated.
Concepts Disease or Syndrome (T047)
MSH D001172
ICD9 714.0
ICD10 M06.9 , M06.99
SnomedCT 156471009, 287010008, 156481008, 69896004
LNC LP30644-6, LA15161-5
English Arthritis, Rheumatoid, ARTHRITIS RHEUMATOID, Rheumatoid Arthritis, Rheumatoid arthritis, unspecified, RHEUMATOID ARTHRITIS, RHEUMATOID ARTHRITIS, SUSCEPTIBILITY TO, Rheumatoid arthritis NOS, rheumatoid arthritis, RA (rheumatoid arthritis), rheumatoid arthritis (diagnosis), R arthritis, Rh arthritis, Arthritis rheumatoid, Systemic rheumatoid arthritis, RA, Arthritis, Rheumatoid [Disease/Finding], Rheumatoid arthritis, unspecified, site unspecified, rheumatoid arthritis systemic, gout rheumatic, proliferative arthritis, atrophic arthritis, Rheumatoid arthritis NOS (disorder), ARTHRITIS, RHEUMATOID, Rheumatoid arthritis, Atrophic arthritis, Chronic rheumatic arthritis, Rheumatic gout, RA - Rheumatoid arthritis, RhA - Rheumatoid arthritis, Rheumatoid disease, Rheumatoid arthritis (disorder), atrophic; arthritis, rheumatoid; arthritis, arthritis; atrophic, arthritis; rheumatoid, Atrophic Arthritis, Arthritis or polyarthritis, atrophic, Arthritis or polyarthritis, rheumatic
Portuguese ARTRITE REUMATOIDE, Artrite reactiva reumatóide, Artrite atrófica, Artrite reumatóide sistémica, Artrite Reumatoide, Artrite reumatóide
Spanish ARTRITIS REUMATOIDE, Artritis reumatoide sistémica, Artritis R, Artritis Re, Artritis atrófica, AR, Artritis Reumatoidea, artritis reumatoide, SAI, Rheumatoid arthritis NOS, artritis reumatoide, SAI (trastorno), artritis atrófica, artritis reumatoide (trastorno), artritis reumatoide, artritis reumática crónica, gota reumática, Artritis reumatoide, Artritis Reumatoide
Dutch systemische reumatoïde artritis, atrofische artritis, RA, reumatische artritis, artritis; atrofisch, artritis; reumatoïd, atrofisch; artritis, reumatoïd; artritis, Reumatoïde artritis, niet gespecificeerd, reumatoïde artritis, Artritis, reumatoïde, Reumatoïde artritis
French Arthrite d, Arthrite rhumatoïde systémique, AR, Polyarthrite rh, ARTHRITE RHUMATOIDE, Polyarthrite rhumatismale, PCE (Polyarthrite Chronique Évolutive), Polyarthrite chronique évolutive, Polyarthrite rhumatoïde, PR (Polyarthrite Rhumatoïde)
German systemische rheumatische Arthritis, atrophische Arthritis, Rh Arthritis, RA, R Arthritis, ARTHRITIS RHEUMATOID, Chronische Polyarthritis, nicht naeher bezeichnet, rheumatoide Arthritis, Arthritis, rheumatoide, Rheumatoide Arthritis, PcP (Primär-chronische Polyarthritis), Polyarthritis, primär chronische, Primär-chronische Polyarthritis
Italian Artrite reumatoide sistemica, AR, Artrite atrofica, Artrite reumatoide
Japanese 全身性関節リウマチ, イシュクセイカンセツエン, ゼンシンセイカンセツリウマチ, カンセツリウマチ, 関節リウマチ, 萎縮性関節炎, リウマチ様関節炎, 慢性関節リウマチ, 関節リウマチ-慢性, 関節炎-リウマチ様
Swedish Ledgångsreumatism
Czech polyartritida progresivní, Systémová revmatoidní artritida, Revmatoidní artritida, Atrofická artritida, artritida revmatoidní, revmatoidní artritida
Finnish Nivelreuma
Russian ARTRIT REVMATOIDNYI, ARTRIT INFEKTSIONNYI NESPETSIFICHESKII, POLIARTRIT REVMATOIDNYI, АРТРИТ ИНФЕКЦИОННЫЙ НЕСПЕЦИФИЧЕСКИЙ, АРТРИТ РЕВМАТОИДНЫЙ, ПОЛИАРТРИТ РЕВМАТОИДНЫЙ
Korean 상세불명의 류마티스 관절염
Croatian ARTRITIS, REUMATOIDNI
Polish Zapalenie stawów reumatoidalne, Gościec przewlekły postępujący, RZS, Reumatoidalne zapalenie stawów, Gościec pierwotnie przewlekły, Zapalenie gośćcowe
Hungarian RA (rheumatoid arthritis), Rheumatoid arthritis, Atrophiás arthritis, R arthritis, Rh arthritis, Systemás rheumatoid arthritis
Norwegian Artritt, revmatoid, Leddgikt, Revmatoid artritt