• Clinical science

Rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction. RA predominantly affects women and middle-aged individuals. The condition can also cause various extra-articular manifestations such as rheumatoid nodules and pulmonary fibrosis. Diagnosis is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically Late-onset for diagnosis. Early intervention with disease-modifying antirheumatic drugs (DMARDs) plays a decisive role in successful treatment. RA is not curable, but early effective treatment may help offset severe complications (e.g., permanent damage to the affected joints).

Epidemiology

  • Prevalence: ∼ 1% of the population
  • Sex: > (3:1)
  • Peak incidence: 50–75 years

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Chronic inflammatory autoimmune disorder of unknown etiology
  • Hypotheses suggest the etiology is multifactorial, with the following factors playing a role:
    • Genetic disposition; : RA appears to be associated with specific HLA types (HLA-DR4, HLA-DR1). [3].
    • Environmental triggers (e.g., infection, tobacco)
    • Hormonal factors

References:[4][5]

Pathophysiology

  • Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells (autoimmune response).
  • With time, it may lead to inflammatory joint effusion and synovial hypertrophy, as well as progressive destruction and deterioration of cartilage and bone.
  • Patients with positive rheumatoid factor (RF) are more likely to develop extra-articular manifestations of rheumatoid arthritis. [6]

References:[7][8]

Clinical features

Articular manifestations

DIP joints are not typically affected in RA!

Extra-articular manifestations

References:[5][9][10][11][12][13][14]

Subtypes and variants

RA of the cervical spine

RA normally spares the thoracic and lumbar spine. In some cases, it initially affects the cervical spine, causing early-morning neck pain at rest.

Felty syndrome

If a patient has arthritis, splenomegaly, and neutropenia, consider Felty syndrome.

Adult Still disease

Other subtypes

References:[15][16][17][18][19]

Diagnostics

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) [20]

  • Rheumatoid arthritis = score of ≥ 6 points + confirmed presence of synovitis in at least one typical joint without an alternative, more probable diagnosis (e.g., trauma or degenerative joint conditions)
    • For every column, the highest score is taken into account.
Points Joint involvement (pain/swelling) Serology Acute phase reactants Duration of symptoms*
0 ≤ 1 large joints** Negative RF and ACPA Normal CRP and ESR < 6 weeks
1 2–10 large joints CRP or ESR ≥ 6 weeks
2 1–3 small joints Low positive RF or ACPA
3 4–10 small joints High positive RF or ACPA (> three times higher than normal)
5

> 10 joints (at least one small joint)

Key

Laboratory tests

Imaging

  • Conventional x-ray
    • Dorso-palmar x-ray of both hands
    • Radiological findings
      • Early: soft tissue swelling, demineralization (juxta‑articular)
      • Late: joint space narrowing, erosions of cartilage and bone, demineralization (generalized)

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

Radiological changes classified by Steinbrocker

Stade Radiological changes Joint mobility
0 Clinical signs, normal x-ray Fully maintained
I Periarticular osteoporosis and changes in soft tissue Fully maintained
II Additional lesions of cartilage and bones Slightly impaired
III Additional subluxations/malposition Significantly impaired
IV Destructive joints, total luxation, ankylosis Completely restricted
  • MRI: (with or without contrast), especially if cervical spine involvement is suspected or in early stages
  • Ultrasound: joint effusion, formation of pannus
  • Further diagnostic measures: contrast-enhanced ultrasound, scintigraphy

Before undergoing general anesthesia, airway and neck assessment is crucial in patients with rheumatoid arthritis. Atlanto-axial 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).

References:[15][5][20][21][22][23][24][25][26]

Pathology

  • Synovial pannus formation and bone invasion; : proliferative granulation tissue with mononuclear inflammatory cells
  • Angiogenesis
  • Synovial lining hyperplasia with mononuclear cell infiltrate
  • Perivascular inflammatory infiltrates
  • Fibrin deposition on synovial surfaces
  • Characteristic histology of rheumatoid nodules: central fibrinoid necrosis with histiocytes and surrounding epithelioid cells

References:[27][28][29][30]

Differential diagnoses

Differential diagnoses of inflammatory arthritis

Condition:

Osteoarthritis

(most common)

Rheumatoid Arthritis (RA) Psoriatic arthritis Gout Pseudogout

Specific groups

  • Sex: >
  • Majority of people > 65 years have radiological evidence of osteoarthritis which may be asymptomatic
  • >
  • Family history of RA
  • Sex: =
  • Family or personal history of psoriasis
  • May be triggered by trauma or infections (e.g., HIV infection)
  • Sex: <
  • Peak incidence: 30–60 years
  • Family history of Gout
  • Often in alcoholics
  • Sex: =
  • Mostly older patients (> 50 years)

Course of disease

  • Chronic, progressive course
  • Chronic course with varied patterns: either monocyclic, polycyclic or progressive
  • Chronic, progressive course
  • Chronic course with acute attacks (rapid onset of symptoms)

Clinical features

  • No constitutional symptoms
  • Morning stiffness < 30 minutes
  • Pain/stiffness worsens with increased activity and relieved by rest
  • Non-inflammatory
  • Constitutional symptoms
  • Morning stiffness > 30 minutes
  • Pain/stiffness can be relieved by activity
  • Articular inflammation (swollen, warm joints)
  • Psoriatic skin lesions and nail changes
  • Dactylitis with “sausage digits”
  • Enthesitis
Symmetry of joint involvement
  • Usually asymmetrical
  • Symmetrical
  • Symmetrical
  • Asymmetrical
  • Asymmetrical

Pattern of disease

  • Polyarthritis
    • Predominantly weight-bearing joints (e.g., knees)
    • Spares the wrist and the MCP joints
  • Polyarthritis: predominantly wrists, MCP and PIP joints

  • Polyarthritis or oligoarthritis
    • Commonly DIPJ and/or spinal involvement
    • Sometimes large joints
  • Usually monoarthritis: typical locations include the big toe (MTPJ), knee and thumb (MCPJ)
  • Monoarthritis (rarely oligoarthritis): commonly knees and wrist joints

Other differential diagnoses:

References:[31][32]

The differential diagnoses listed here are not exhaustive.

Treatment

General measures

  • For acute episodes of inflammation: cryotherapy
  • Physical and occupational therapy
  • Physical activity

Acute anti-inflammatory therapy

  • Indication: acute attack
  • Glucocorticoids; : given until DMARD's onset of action or as long-term therapy for highly active RA.
    • Systemic
    • Intra-articular injections of PRN
    • Prevention of osteoporosis: optimization of sufficient calcium and vitamin D intake
  • NSAIDs and COX-2 inhibitors: symptomatic relief without improving prognosis

Long-term anti-inflammatory therapy with disease-modifying antirheumatic drugs (DMARDs)

Early administration of DMARDs is crucial for a better outcome!

Interventional

Surgical intervention may contribute to pain relief, deformity correction, and functional improvement. However, indications evolve individually. Sometimes early intervention may help to maintain quality of life.

References:[34][4][5][35][36][37][38]

Complications

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

References:[39][5][40][41][42]

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

Prognosis

  • Factors associated with poor prognosis
    • Prolonged disease progression without initiation of treatment
    • Late onset (> 60 years of age)
    • Sex:
    • Smoking
    • Social factors (e.g., low socioeconomic status, low level of education)
  • Laboratory tests associated with worsened prognosis if abnormally elevated

References:[5][37]