Basics
Description
- Rheumatoid arthritis (RA) is a chronic, multisystem, inflammatory, autoimmune disease.
- Inflammation of the joints can lead to cartilage destruction and inability to function.
Epidemiology
- RA is a relatively common autoimmune disease.
- Females > Males (4:1)
- Bimodal peak age of onset in women between 31 and 35, then after age 46
Incidence
Annual incidence of 0.2/1,000 males and 0.4/1,000 females and increases with age
Prevalence
- Affects 1% of the US population
- Worldwide: 0.8% of the adults
Risk Factors
- The following are associated with a higher incidence of RA, but not necessarily linked to causation.
- Hormonal influence
- Environmental factors
- Tobacco (main environmental risk)
- Coffee consumption
Genetics
- 50% of the risk factors for RA are attributable to genetic factors and include:
- HLA-DRB1 alleles
- Twin studies have heritability of 60%.
- Siblings have a 2- to 4-fold risk of developing RA.
Pathophysiology
- Immune-mediated disease
- CD4+ T cells induce an immune response from unknown endogenous or exogenous antigens.
- Monocytes, macrophages, and fibroblasts are recruited and produce TNF-alpha and IL-1 within synovium.
- Matrix metalloproteinases and osteoclasts are then triggered, which results in joint damage.
Etiology
- Unknown
- RA is thought to be multifactorial with genetic and environmental factors playing a role.
Associated Conditions
- There are multiple coexisting conditions associated with RA that impact prognosis. Some important ones to consider include:
- Infection: Incidence doubled in RA
- Osteoporosis: Incidence doubled in RA
- Cardiovascular disease: Accounts for most of the mortality in RA
- Malignancy: Increased 5 " 8 times over the rate of general population
RA goes into remission during pregnancy approximately 75% of the time, but about 80% of women experience a flare postpartum.
Diagnosis
New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria recently developed in 2010 based on number of joints involved and laboratory findings (1)[A]
History
- Gradual onset of joint pain and swelling
- Morning stiffness >1 hour
- Fatigue
- Inability to perform daily activities
Physical Exam
- Tenderness, warmth, and swelling of joints
- Joint effusions
- Decreased range of motion of affected joints
- Subcutaneous nodules
Tests
Lab
- Rheumatoid factor (RF)
- Present in 60 " 85% of cases of RA, but specificity is low
- High titer does have prognostic role and is associated with more severe diseases such as erosions, subcutaneous nodules, and extra-articular manifestations.
- Antibodies to cyclic citrullinated antigens (CCP)
- Highest specificity of any antibody: 95%
- Sensitivity: 50 " 70%
- Already present in patients with very early RA and may be associated with more severe disease
- Can also see anemia of chronic disease, elevated platelet count, ESR, and CRP
Imaging
- There are some findings on plain x-ray that are suggestive of RA including:
- Fusiform soft tissue swelling
- Periarticular osteoporosis
- Juxta-articular erosions and cysts
- Loss of joint space
- MRI and ultrasound detect erosions, cysts, and effusions that may not be seen on plain x-ray.
Differential Diagnosis
- Differential diagnosis of a patient with polyarthritis
- Inflammatory disease
- Psoriatic arthritis
- Reactive arthritis
- Spondyloarthropathy
- Crystal arthropathy
- Systemic lupus erythematosus
- Polymyalgia rheumatica
- Viral infection
- Parvovirus B19
- Hepatitis B
Treatment
- Joint damage occurs early, and 30% of patients have radiographic evidence of bony erosions at time of diagnosis, so early intervention is key (2)[A].
- Goals are remission of symptoms with no active joint inflammation and no erosive or functional deterioration.
Medication
- 3 categories:
- NSAIDs
- Corticosteroids
- Disease-modifying antirheumatic drugs (DMARDs)
First Line
- DMARDs (2)[A]
- Reduce joint swelling and pain, decrease acute-phase markers, limit progressive joint damage, and improve function
- Should be started within 3 months after onset of symptoms
- Methotrexate (MTX) is considered the first line unless contraindicated (2)[A].
- Should not be used in patients with underlying liver disease or history of heavy alcohol use
- Concomitant use of folic acid (1 " 3 mg/day) significantly decreases side effects.
- Aminotransferase, albumin, and CBC should be monitored every 8 weeks.
- Leflunomide: Similar to MTX; long half-life
- Adverse effects include myelosuppression and hepatic fibrosis.
- Should monitor CBC, AST, ALT, albumin every 8 weeks
- Sulfasalazine: Safe to use in patients with liver disease
- Adverse effects include myelosuppression.
- CBC monitored every 2 weeks for first 3 months, then every 3 months
- Hydroxychloroquine: Very well tolerated, effective in mild RA or in combination therapy
- Adverse effects include macular changes.
- Therefore, patients should have funduscopic examination every year.
- Biologic response modifiers are extremely effective medications in inducing clinical and radiographic remission (all are injectable or IV infusions) (3)[A]
- Tumor necrosis factor (TNF) antagonists (3)[A]
- Etanercept: Soluble TNF-receptor fusion protein
- Infliximab: Chimeric IgG anti-TNF-alpha antibody
- Adalimumab: Recombinant human IgG monoclonal antibody
- Golimumab: Recombinant human IgG monoclonal antibody
- Certolizumab pegol: Pegylated TNF-alpha inhibitor
- Adverse effects of these drugs include increased rate of infections, reactivation of latent tuberculosis, lupus-like autoimmune disease, multiple sclerosis-like demyelinating disease, and worsening of heart failure.
- Other biologic response modifiers (4)[A]:
- Anakinra: IL-1 receptor antagonist
- Tocilizumab: Humanized anti-IL-6 receptor antibody
- Rituximab: Chimeric monoclonal antibody that binds to CD20 B cells
- Abatacept: CTLA4 linked to human IgG to decrease second signal activation of T cells
Pregnancy Considerations
- MTX is contraindicated in pregnancy.
- Recommended to discontinue at least 3 months prior to conception
- Leflunomide is contraindicated in pregnancy and should be discontinued 2 years prior to conception, because of its long half-life.
- The mother can undergo treatment with cholestyramine to bind the drug.
- Biologic response modifiers are being studied in pregnancy and safety is not known.
Second Line
- NSAIDs
- Useful in the first few weeks of symptoms for relief of pain and stiffness
- Do not slow progression of disease
- Should be used with DMARD in maintenance therapy
- Corticosteroids
- Can be used to bridge the effect of DMARD, but should not be used alone
- All patients should receive supplemental calcium (1 " 1.5 g/day) and vitamin D (800 IU/day) while receiving corticosteroids.
Additional Treatment
General Measures
The goal of treatment is to induce remission.
Issues for Referral
Referral to a rheumatologist is crucial so that proper diagnosis is made, and early DMARD therapy is initiated within 3 months after the onset of symptoms.
Additional Therapies
- There are several modalities that can provide relief.
- Flexibility, range of motion, and aerobic exercise are all useful.
- Joint protection and energy conservation
- Splinting of hands or wrists or use of lower extremity orthotics can provide temporary pain relief.
Complementary and Alternative Medicine
- Patient education is a proven effective intervention in RA.
- Local Arthritis Foundation chapter has information.
Surgery
There are several surgical procedures for selected patients with severe RA.
- Tenosynovectomy
- Tendon reconstruction
- Joint synovectomy
- Peripheral nerve decompression
- Joint fusion or replacement
Ongoing Care
Follow-Up Recommendations
- Most patients with RA can participate in moderate-intensity aerobic exercise.
- Patients with RA should be followed frequently to monitor toxicities of medical management and disease progression.
Prognosis
- Prognosis has greatly improved with early therapy with DMARDs and newer biologic agents, but there is still significant morbidity associated with RA. Some poor prognostic indicators include:
- Early presence of bony erosions
- Extra-articular features
- Older age at onset
- Positive RF and anti-CCP antibodies
- Genetic factors such as presence of HLA-DR epitopes
- The long-term prognosis and survival also depends on addressing the coexisting conditions as discussed.
Complications
- Tendon rupture
- Synovial rupture of knee
- Entrapment neuropathies
- Septic arthritis
- Instability of cervical spine
- Osteoporosis
References
1Scott D, Wolfe F, Huizinga T. Rheumatoid arthritis. Lancet. 2010;376:1094 " 1108. [View Abstract]2Rau R. Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:S58 " S64. [View Abstract]3Nam JL, Winthrop KL, van Vollenhoven RF. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: A systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69:976 " 986. [View Abstract]4Khraishi M. Comparative overview of safety of the biologics in rheumatoid arthritis. J Rheumatol. 2009;36(Suppl 82):25 " 32.
Codes
ICD9
714.0 Rheumatoid arthritis
ICD10
- M05.9 Rheumatoid arthritis with rheumatoid factor, unspecified
- M06.00 Rheumatoid arthritis without rheumatoid factor, unsp site
- M06.9 Rheumatoid arthritis, unspecified
SNOMED
- 69896004 rheumatoid arthritis (disorder)
- 239792003 seronegative rheumatoid arthritis (disorder)
- 239791005 seropositive rheumatoid arthritis (disorder)
Clinical Pearls
- Multisystem autoimmune disease
- Women in 4th and 5th decade
- Symmetric inflammatory arthritis
- Morning stiffness >1 hour
- Early treatment with DMARDs significantly improves quality of life, morbidity, and disease progression.