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Rheumatoid arthritis

Last updated: May 26, 2021

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Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disorder that primarily affects the joints (e.g., pain, swelling, synovial destruction, deformities) but may also manifest with extraarticular features (e.g., rheumatoid nodules, pulmonary fibrosis). Incidence is highest in women over 65 years of age. Diagnosis is mainly clinical but may also involve laboratory tests (e.g., anti-CCP) and, later in the disease course, x-ray findings (e.g., soft tissue swelling or joint space narrowing). There is no curative therapy, but early intervention with disease-modifying antirheumatic drugs (DMARDs) can reduce the risk of complications (e.g., permanent damage to the affected joints).

  • Prevalence
    • ∼ 0.24% worldwide [1]
    • 1% in northern Europe and US [2]
  • Sex: > (3:1) [3]
  • Peak incidence: > 65 years [4]

Epidemiological data refers to the US, unless otherwise specified.

“A DRone with 4 propellers and 1 camera:” rheumatoid arthritis is associated with HLA-DR4 and HLA-DR1.

Articular manifestations [11]

DIP joints are not typically affected in RA.

Extraarticular manifestations [14]

Rheumatoid arthritis of the cervical spine [12]

RA typically affects the cervical spine early in the course of the disease, while normally sparing the thoracic and lumbar spine. RA of the cervical spine most commonly manifests with atlantoaxial subluxation. Other patterns of instability are atlantoaxial impaction and subaxial subluxation.

Atlantoaxial subluxation

Felty syndrome [12]

Arthritis, splenomegaly, and neutropenia may suggest Felty syndrome.

Adult-onset Still disease


The diagnosis of RA is based on diagnostic criteria that include laboratory testing. Imaging may support the diagnosis, but radiological joint findings are no longer included in the criteria, as they often become evident only in late stages of disease.

ACR criteria for RA (ACR/EULAR classification criteria 2010) [18][20]

  • Rheumatoid arthritis = score of ≥ 6 points + confirmed presence of synovitis in at least one typical joint in the absence of a more probable cause (e.g., trauma or degenerative joint conditions)
  • The total score is obtained by adding the points from each feature.
Points Joint involvement (pain/swelling)* Serology Acute phase reactants Duration of symptoms
0 ≤ 1 large joint Negative RF and ACPA Normal CRP and ESR < 6 weeks
1 2–10 large joints N/A CRP or ESR ≥ 6 weeks
2 1–3 small joints Low positive RF or ACPA N/A N/A
3 4–10 small joints High positive RF or ACPA (> three times higher than normal) N/A N/A

> 10 joints (at least one small joint)


*Large joints comprise the shoulder, elbow, hip, knee, and ankle. Small joints comprise the wrist, metacarpophalangeal joint (MCP), metatarsophalangeal joint (MTP), and proximal interphalangeal joint (PIP) of the hand and the foot.

Laboratory tests

Imaging [25]

Radiological changes classified by Steinbrocker [26]
Stage Radiological changes Joint mobility
  • Clinical signs, normal x-ray
  • Fully maintained
  • Additional lesions of cartilage and/or subchondral bones
  • Slightly impaired
  • Significantly impaired
  • Completely restricted
  • MRI (with or without contrast): especially if cervical spine involvement is suspected or in early stages
  • Ultrasound
    • Joint effusion: increased amount of fluid (e.g., pus, blood, inflammatory infiltrate) within the synovial compartment of a joint
    • Formation of pannus
  • Further diagnostic measures: contrast-enhanced ultrasound and bone scintigraphy are very sensitive to inflammatory arthritis, providing further evaluation of disease activity and therapeutic monitoring of the disease.

Even if radiographic findings are normal, RA is still possible.

Before undergoing general anesthesia, airway and neck assessment is crucial in patients with rheumatoid arthritis. Atlantoaxial subluxation may be present, which increases the risk for spinal cord injury. Preoperative flexion-extension radiographs can help to evaluate the position of the cervical vertebra atlas (C1) with regard to the axis (C2).

Assessment of the disease activity

Typically, periods of minimal or no symptoms alternate with periods of increased disease activity (flares).

Criteria to assess disease activity
Disease activity Joints Fever Extraarticular symptoms Functional impairment
  • Low number of joints involved (< 5)
  • Intermittent pain and/or swelling
  • Sporadic stiffness
  • Absent or low (< 38°C)
  • Absent or sporadic, mild fatigue
  • Minimal
  • 5–10 joints involved
  • Frequent pain, swelling, and morning stiffness
  • Frequently 38°C or above
  • Possible night sweats
  • Fatigue
  • Skin rashes
  • Possible weight loss
  • Difficulty in performing everyday tasks
  • > 10 joints involved (most MCPs and PIPs)
  • Pain and swelling may be constant
  • Deformities
  • Impaired mobility
  • Frequently 38°C or above
  • Night sweats
  • See “Extraarticular manifestations” in “Clinical features” above.
  • Completely debilitating

Differential diagnoses of inflammatory arthritis
Condition Rheumatoid arthritis (RA)


Psoriatic arthritis Gout Pseudogout


  • Sex: >
  • Age (> 55 years)
  • Sex: =
  • Majority of people > 50 years
Risk factors
  • Family history of RA
  • History of joint injury or trauma
  • Obese patients
  • Family or personal history of psoriasis
  • May be triggered by trauma or infections (e.g., HIV infection)

Course of disease

  • Chronic course with varied patterns
    • Monocyclic
    • Polycyclic
    • Progressive
  • Chronic, progressive course
  • Chronic, progressive course
  • Chronic course with acute attacks

Clinical features

  • No constitutional symptoms
  • Morning stiffness < 30 minutes
  • Pain/stiffness worsens with increased activity and relieved by rest
  • Noninflammatory
  • Eventually development of tophi
Symmetry of joint involvement
  • Symmetrical
  • Usually asymmetrical
  • Asymmetrical oligoarticular type
  • Symmetrical polyarthritis type
  • Asymmetrical

Pattern of disease

  • Polyarthritis or oligoarthritis
Laboratory findings
  • No specific laboratory features

The differential diagnoses listed here are not exhaustive.

General measures

  • Physical and occupational therapy
  • Physical activity
  • Application of heat or cold packs as needed

Acute antiinflammatory therapy

Long-term antiinflammatory therapy with disease-modifying antirheumatic drugs (DMARDs) [28][29][30]

General information

  • Induces immunosuppression, leading to potential remission of RA
  • Should be initiated regardless of the disease activity
  • DMARD monotherapy is preferred for any level of disease activity
  • Treat-to-target strategy should be used
  • DMARD therapy reduces mortality and morbidity by up to 30% [12]
    • Slows progression of disease
    • Preserves joint function
    • Limits RA complications
  • Slow onset of action (≥ 6 weeks); symptomatic treatment with glucocorticoids and/or NSAIDs is often required

Nonbiologic agents

Biologic agents [5][28]

Early administration of DMARDs is crucial for a better outcome.


Surgical intervention may help relieve pain, correct deformity, and improve function. However, indication should be considered on an individual basis. Sometimes early surgical intervention may help to maintain quality of life.

  • Radiation synovectomy: ablation of inflamed synovia via injection of radioactive agents (beta particles) into the synovial cavity of the affected joint
    • Inhibits synovial growth and fibrosis of the synovia
    • May reduce inflammatory activity and pain
    • Also indicated for other therapy-resistant chronic inflammatory joint diseases (e.g., active arthrosis or psoriatic arthritis)
  • Synovectomy: surgical removal of the synovial tissue

Untreated and/or severe cases can result in permanent damage to the joints with stiffening and deformity.

We list the most important complications. The selection is not exhaustive.

  • Factors associated with poor prognosis
    • Cardiovascular disease and infections are the most common causes of death. [12]
    • Male sex [34]
    • Smoking
    • Social factors (e.g., low socioeconomic status, low level of education)
    • Presence of extraarticular disease
  • Elevated laboratory values associated with poor prognosis
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