Overview

Rheumatoid arthritis (RA, ‘rheuma’ – watery, ‘arthritis’ – joint inflammation) is an autoimmune disorder characterised by inflammation of the synovial membrane leading to joint swelling, tenderness, warmth, and stiffness. This can also lead to destruction of the surrounding tissues and the joint. RA may also have extra-articular disorders.

Epidemiology

  • RA is the most common type of inflammatory arthritis
  • It affects around 1% of the UK’s population
  • Its onset can occur at any age, but peaks in people aged 30-50 years
  • RA is 2-4 times more common in women than men

Risk Factors

  • Family history
  • Smoking
  • HLA-DR4 or HLA-DR1

Presentation

RA typically presents with an insidious onset (generally over months) of symmetrical polyarthritis (arthritis affecting both sides equally) affecting the small joints of the hand and feet. Some patients may have rapid, relapsing and remitting symptoms and this is known as palindromic rheumatism.

RA presents with persistent synovitis (lasting a few weeks rather than days) characterised by:

  • Inflammatory-type pain and stiffness:
    • These are both worse with rest and improve with exercise
    • Prolonged morning stiffness (usually >1 hour) is typically seen
  • Joint erythema and joint warmth. The most commonly affected joints are:
    • Metacarpophalangeal (MCP)
    • Proximal interphalangeal (PIP)
    • Metatarsophalangeal (MTP)
  • Joint swelling:
    • Usually ‘boggy’ or ‘squishy’ swelling around the joint
    • Not bone swelling which is hard and not boggy
  • A positive MCP squeeze test may be seen – squeezing the MCP joints elicits pain
  • The patient may not be able to make a fist or flex the fingers

Additional features include:

  • Rheumatoid nodules – hard swellings over extensor surfaces
  • Extra-articular features (vasculitis or eye, lung, or heart involvement)
  • Systemic upset (fever, fatigue, weight loss, night sweats, malaise)

Signs on examination

  • ‘Boggy’ swellings around joints
  • Swan neck deformity – late-stage sign
  • Boutonniere’s deformity – late-stage sign
  • Ulnar deviation due to MCP inflammation
  • Rheumatoid nodules on extensor surfaces of tendons

Differential Diagnoses

Osteoarthritis (OA)

  • Joint pain and stiffness are worse with activity and improve with rest
  • OA tends to spare the MCP joints
  • OA tends to affect larger joints such as the knee, hips, and lumbar spine

Psoriatic arthritis

  • Tends to affect fewer joints (oligoarthritis, <5 joints)
  • Tends to affect joints asymmetrically
  • Psoriasis may be present
  • Nail changes may be present (such as nail pitting or onycholysis) 

Reactive arthritis

  • Usually occurs a few weeks after a sexually-transmitted infection or gastroenteritis
  • There may be associated conjunctivitis and urethritis

Gout and pseudogout

  • These tend to present more acutely (over hours) and affect one or two joints
  • Some patients may have polyarticular gout that can mimic RA
  • Gouty tophi may be seen in gout, which helps differentiate it from RA

Systemic lupus erythematosus (SLE)

  • Arthritis in SLE is generally non-deforming
  • There are associated features of SLE such as a skin rash, mouth ulcers, alopecia, and Raynaud’s syndrome

Investigations

Referral

All patients with persistent synovitis with no obvious underlying cause should urgently be referred to rheumatology for specialist assessment and to confirm the diagnosis.

All patients

Investigations may be performed in primary care while a patient is being referred to speed up the diagnostic process, however, they should not delay a patient’s referral. Initial investigations include:

  • Rheumatoid factor (RF):
    • High sensitivity, but around 1/3 of patients are RF-negative
  • Anti-cyclic citrullinated peptide (anti-CCP) antibody:
    • High specificity, positive in around 80% of people with RA
  • X-ray of the hands and feet – in all patients with RA:
    • Helps with diagnosis and determination of disease severity
    • May show loss of joint space, juxta-articular osteoporosis, soft tissue swelling, periarticular erosions, or subluxation

Other investigations to consider are:

Management

In primary care

Consider offering an NSAID and proton pump inhibitor while awaiting a rheumatology appointment for symptomatic relief.

If a flare of RA occurs, rule out septic arthritis, seek specialist advice and offer short-term glucocorticoid treatment, which may involve:

  • Intra-articular glucocorticoid, intramuscular glucocorticoid, or oral glucocorticoids 

In secondary care

  • 1st-line: conventional disease-modifying antirheumatic drug (cDMARD) + short-term glucocorticoid bridging therapy (oral, intramuscular, or intra-articular) while waiting for the cDMARD to take effect (around 2-3 months). Options include:
    • Methotrexate + folic acid to reduce the risk of side effects
      • Side effects: mouth ulcers, pneumonitis, bone marrow suppression, teratogenic – avoid in pregnancy
    • Leflunomide
      • Side effects: interstitial lung disease, liver impairment, hypertension, mouth ulcers, bone marrow suppression, teratogenic – avoid in pregnancy
    • Sulfasalazine
      • Side effects: skin rashes, oligospermia, bone marrow suppression
    • Hydroxychloroquine:
      • Side effects: reduced visual acuity due to retinopathy – patients need regular ophthalmology assessments (usually yearly)
  • 2nd-line: if there is an inadequate response to at least 2 cDMARDs including methotrexate, consider biologic DMARDs:
    • TNF inhibitors – may risk reactivation of tuberculosis, screen for TB using a chest x-ray if appropriate:
      • Adalimumab
      • Etanercept
      • Golimumab
      • Infliximab
    • B-cell inhibitors:
      • Rituximab

Pregnancy

Overview

In general:

  • Methotrexate is teratogenic and should be stopped at least 6 months in both men and women before attempting to conceive
  • Low-dose daily corticosteroids are the safest option
    • Hydroxychloroquine and sulfasalazine are considered safe for pregnancy
  • Refer patients to an obstetric anaesthetist due to the risk of atlantoaxial subluxation

Monitoring

DMARDs require regular monitoring with blood tests. This is discussed in Disease-Modifying Antirheumatic Drugs (DMARDs).

Complications

  • Neurological:
    • Mononeuritis multiplex
    • Carpal tunnel syndrome
    • Atlanto-axial subluxation – subluxation between C1 and C2 can lead to spinal cord compression, quadriplegia, and death
      • Pre-operative MRI scans are performed in patients with RA to assess for this, as it can cause complications during intubation
  • Dermatological – rheumatoid nodules – hard skin lesions on extensor surfaces
  • Pulmonary – pulmonary fibrosis
  • Cardiovascular:
  • Haematological:
  • Ophthalmic:

Prognosis

  • RA usually follows periods of acute flares followed by periods of remission
  • Around 1/3 of people with RA stop work within 2 years of its onset
  • A worse prognosis is associated with:
    • RF and/or anti-CCP antibodies present
    • Insidious onset
    • Poor functional status at presentation
    • Early X-rays showing bone lesions
    • Extra-articular manifestations

Author