Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune chronic inflammatory disorder. It is characterised by an inflammation of the synovial joints leading to joint and periarticular tissue destruction as well as a wide variety of extra-articular features.
The American College of Rheumatology identified seven diagnostic criteria for rheumatoid arthritis.¹ Four of the following seven criteria must be met:

1. Morning stiffness in and around joints lasting 1 hour or more before maximal improvement (must have been present for at least 6 weeks).
2. Soft tissue swelling (arthritis) of three or more joint areas (must have been present for at least 6 weeks).
3. Swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints (must have been present for at least 6 weeks).
4. Symmetrical arthritis (must have been present for at least 6 weeks).
5. Subcutaneous nodules.
6. Positive test for rheumatoid factor.
7. Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.

• Prevalence ranges from 0.5-1.5% of the population in industrialised countries
• Peak incidence occurs between the ages of 40 and 50
• The annual incidence in women was recently estimated at 36 per 100,000 and in men at 14 per 100,000 (ratio 2.5:1).

Risk Factors

• The evidence suggests that the cause is multifactorial in people with genetic susceptibility
• HLA DR4 and DR1 are associated, especially in severe disease
• Possible infective aetiology, although no organism has been demonstrated
• Onset is more common in winter.

Can be very variable.

Symptoms

• It usually starts as an insidious symmetrical polyarthritis, often with non-specific systemic symptoms
• Pain
• Swelling
• Stiffness, especially early morning or after inactivity
• Fatigue, fever and weight loss are common.

Signs

Classically:

• Symmetrical, distal, small joint arthritis involving proximal interphalangeal, metacarpophalangeal, wrists, metatarsophalangeal, ankles, knees and cervical spine joints
• Shoulders, elbows and hips are less commonly affected
• Hand deformities, including ulnar deviation, swan neck and Boutonniere's of the fingers, Z deformities of thumbs and piano key deformity of wrist
• Muscle wasting and tendon rupture
• Occasionally may present atypically as a monoarthritis, sudden onset, or systemic illness with minimal joint problems at first (especially in men).This is known as Palindromic Rheumatoid Arthritis.

Systemic involvement

• Eyes: Secondary Sjogren's syndrome, scleritis and episcleritis
• Skin: Leg ulcers especially in Felty's syndrome (association of Rheumatoid factor positive rheumatoid arthritis, neutropenia and splenomegaly). Rashes, nail fold infarcts
• Rheumatoid nodules: Common; may occur in eyes, subcutaneous, lung, heart and occasionally vocal cords
• Neurological: peripheral nerve entrapment, atlanto-axial subluxation, polyneuropathy, mononeuritis multiplex
• Respiratory system: pleural involvement, pulmonary fibrosis, obliterative bronchiolitis, Caplan's syndrome
• Cardiovascular system: pericardial involvement, valvulitis and myocardial fibrosis, immune complex vasculitis
• Kidneys: rare including analgesic nephropathy. Amyloidosis
• Liver: mild hepatomegaly and abnormal transaminases common
• Other: thyroid disorders, osteoporosis, depression, splenomegaly.

Differential Diagnosis includes²:

• Viral arthritis (e.g. parvovirus, rubella, hepatitis B)
• Reactive arthritis (e.g. postinfective: throat, gut, sexually acquired)
• Seronegative spondyloarthropathy (e.g. psoriatic, ankylosing spondylitis, inflammatory bowel disease)
• Connective-tissue disease (e.g. systemic lupus erythematosus, scleroderma)
• Polymyalgia rheumatica.
• Polyarticular gout.
• Osteoarthritis (e.g. involvement of proximal and distal interphalangeal joints, Heberden or Bouchard nodes)
• Septic arthritis (particularly if monoarthritis)
• Fibromyalgia.
• Lyme disease.
• Medical conditions presenting with arthropathy, e.g. sarcoidosis, thyroid disease, infective endocarditis, haemochromatosis, diabetic cheiroarthropathy, paraneoplastic syndromes, multiple myeloma.

Diagnosis is essentially clinical and there is no diagnostic investigation. Investigations are important in assessment and exclusion of other possible diagnoses.

• ESR, CRP and plasma viscosity: usually raised but may be normal
• Full blood count: normochromic, normocytic anaemia and reactive thrombocytosis common in active disease. Raised ferritin but low serum iron concentration and total iron binding capacity.
• Liver function tests: mild elevation of alkaline phosphatase and gamma GT.
• Uric acid/synovial fluid analysis: excludes polyarticular gout
• Urinalysis: microscopic haematuria/proteinuria may suggest connective tissue disease
• Rheumatoid Factor: positive in 60-70% of patients (and 5% of normal population).
• Antinuclear antibody: positive in SLE and related conditions; also in up to 30% of rheumatoid arthritis patients and weakly positive in up to 10% of the normal population.
• Radiology: X-Rays may show soft tissue swelling, periarticular osteopenia, loss of joint space, erosions and deformity.

The British Society for Rheumatology has published guidance on the standards of care for people with rheumatoid arthritis.⁴ Early involvement of secondary care is very important for establishing the diagnosis, early use of disease modifying anti-rheumatic drugs (DMARDs) and ensuring full access to all available resources.
See Management of Rheumatoid Arthritis and Rheumatological Drugs and Their Monitoring.

• Adverse effects on work and social life are common
• Many people with rheumatoid arthritis (RA) have restricted mobility and difficulties with activities of daily living
• Depression is common
• Inability to work may occur early in the course of the disease, especially in someone with a manual occupation
• Inflammatory conditions other than those involving joint and tendon
• Vasculitis, vasculitic ulcers
• Pleurisy/pleural effusions, pulmonary fibrosis
• Pericarditis
• Lymphadenopathy
• Dry-eye syndrome (keratoconjunctivitis sicca)
• Neuropathy
• Felty's syndrome (enlarged spleen and low white-cell count); can present with an infection or leg ulcer
• Amyloidosis (rare)
• Anaemia
• Orthopaedic complications: carpal tunnel syndrome, tendon rupture (particularly extensors of fingers or thumb), cervical myelopathy (usually after severe and long-standing RA), osteoporosis
• Infectious complications: increased risk of infections. Pulmonary infection and generalized sepsis are particular risks. Septic arthritis is a rare but serious complication.

• Some people experience flares and remissions, and others a progressive course. Over the years, structural damage occurs, leading to articular deformities and functional impairment.
• The condition reduces life expectancy but prognosis is variable(20% one attack only whereas nearly 90% of patients with severe disease will be clinically disabled in 20 years).
• About half of people will be unable to work within 10 years
• Poorer prognosis associated with:
  • Insidious onset
  • Male sex
  • Extra-articular manifestations
  • Functional disability at 1 year after start of disease
  • High RF titres
  • HLA-DR4 present
  • X-Ray evidence of erosions within 3 years.