Rheumatoid arthritis (RA)

RA is a chronic symmetrical polyarthritis of unexplained cause. It is a systemic disorder characterized by chronic inflammatory synovitis pf mainly peripheral joints. Its course is extremely variable and it is associated with non-articular features.

Pathology:

• Widespread persisting synovitis (inflammation of the synovial lining of joints, tendon sheaths or bursae)
• Unknown mechanism but the production of rheumatoid factors (RFs) is thought to be important
• The synovium becomes greatly thickened to the extent that it is palpable as a ‘boggy’ swelling around the joints and tendons
• There is marked vascular proliferation
• Increased permeability blood vessels and the synovial lining layer leads to joint effusions
• The hyperplastic synovium spreads from the joint margins on to the cartilage surface. This ‘pannus’ of inflamed synovium damages the underlying cartilage by blocking its normal route for nutrition and the direct effect of cytokines on the chondrocytes

Rheumatoid factors (RFs):

• These are circulating antibodies which have the F_c portion of Ig as their antigen
• The nature of the antigen means that they self-aggregate into immune complexes and thus activate complement and stimulate inflammation – causing chronic synovitis
• Transient production of RFs is essential for removing immune complexes
• RFs may be of any Ig class but are most commonly IgM
• ~70% of patients with polyarticular RA have IgM RF in their serum
• The term seronegative RA is used for patients in whom the standard tests for IgM RF are persistently negative

Typical presentation:

• ~70% of cases begin as a slowly progressive, symmetrical, peripheral polyarthritis
• Usual timescale is a few weeks or months
• Women 3x > men
• Peak age of onset is 30-40 (can occur at any age)
• 15% of patients have a rapid onset of symptoms (occurring over a few days or even overnight). Surprisingly, these patients have a better prognosis
• bad prognostic signs include:
• female
• gradual onset over a few months
• positive IgM RF
• anaemia occurring within the first 3 months

Symptoms and signs:

• Pain and stiffness of the PIPs, DIPs, MCPs and MTPs
• The wrists, elbows, shoulders, knees and ankles are also affected
• Only 10% of patients present with a monoarthritis (usually the knee, shoulder or carpal tunnel syndrome)
• Lethargy
• Malaise
• Pain and stiffness significantly WORSE IN THE MORNING and may improve with gentle activity
• The joints are usually warm and tender with some joint swelling
• Limitation of movement
• Muscle wasting
• Deformities develop as the disease progresses

Complications:

Of the disease:

• Ruptured tendons

• Joint infection (septic arthritis)
• Ruptured joints (e.g. Baker’s cysts)
• Spinal cord compression
• Amyloidosis

Of the therapy:

• Anaemia
• Marrow hypoplasia
• Renal impairment
• GI bleeding

Septic arthritis:

• Serious complication with a high mortality
• The joint(s) may be hot, inflamed with accompanying fever
• Increased WCC
• However, these signs can be absent and any effusion (particularly of sudden onset) should be aspirated
• Staph. aureus is the most common organism
• Treatment is with systemic antibiotics

Amyloidosis:

• Is found in a small number of cases of severe RA
• RA is the most common cause of secondary amyloidosis

Non-articular manifestations of RA:

• Sclerosis

• Scleromalacia
• Sjogren’s syndrome (dry eyes, dry mouth)
• Atlanto-axial subluxation (rarely causing c-spine compression)
• Vasculitis
• Pleural effusion
• Fibrosing alveolitis
• Small airway disease
• Lymphadenopathy
• Pericarditis
• Bursitis
• Anaemia
• Carpal tunnel syndrome
• Amyloidosis (causes the nephrotic syndrome and renal failure)
• Sensorimotor polyneuropathy (caused by vasculitis of the vasa nervorum)
• Leg ulcers
• Ankle oedema
• Splenomegaly

Criteria for the diagnosis of RA:

For 6 weeks or more:

• Morning stiffness for >1 hour
• Arthritis of 3 or more joints
• Arthritis of hand joints and wrists
• Symmetrical arthritis

For any length of time:

• Subcutaneous nodules
• Positive serum RF
• Typical radiological changes

4 or more are necessary for diagnosis

X-ray changes in RA:

• Juxta-articular osteoporosis
• Joint-space narrowing
• Bony erosions

Drug therapy:

Essentially comprises 3 main groups of drugs:

• NSAIDs (Non-steroidal anti-inflammatory drugs)
• DMARDs (Disease modifying anti-rheumatic drugs)
• Corticosteroids

NSAIDs:

• Control the pain and stiffness but do not reduce the underlying inflammatory relapse or the acute flare reactants in the serum
• Always start with a familiar drug. It should be cheap, have a low incidence of side-effects and a convenient dosage schedule
• Major side-effects of NSAIDs are gastrointestinal:
• Haemorrhage a major problem in the elderly
• Pts with previous PUD should have their H. pylori status checked, followed by eradication therapy if required
• Risks can be reduced by the co-administration of H₂-receptor antagonists or PPIs

• Other side-effects include:
• Fluid retention
• Tubulo-interstitial nephritis
• Drug interactions

DMARDs:

Sulphasalazine 1-1.5g BD PO

Methotrexate 2.5-15mg once weekly PO (remember folate supplementation)

Gold 3mg BD PO or 50mg weekly IM

Penicillmine 250-400mg AC PO

Antimalarials 400mg OD PO

It should be noted that DMARDs are almost exclusively prescribed by a rheumatologist and that each drug has numerous side-effects

Corticosteroids:

The use of oral corticosteroids has a number of problems:

1. Patients are increasingly anxious about the use of corticosteroids because of adverse publicity about their potential side-effects
2. Risk of weight gain
3. Skin becomes thin and easily damaged
4. Monitor for DM and HT
5. Cataract formation may be accelerated
6. Osteoporosis develops within 6 months on doses >7.5mg daily and HRT and/or calcium and vitamin D or bisphosphonate is used

• Must be avoided in the long-term
• Intra-articular injections have a powerful but short-lived effect
• IM depot injections (40-120mg depot methylprednisolone) help to control severe flare-ups of the disease; or can be used before a holiday or other important event but should be used with caution and infrequently