Rheumatoid Arthritis: Features, Antibodies and DMARDs

Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly causes inflammation of the joints. Without treatment it leads to joint damage, deformity and disability. Early diagnosis and early treatment with disease-modifying drugs dramatically improve outcomes. There is a "window of opportunity" in the first months.

Who gets it

RA is about two to three times more common in women, and often starts between the ages of 30 and 60. Risk factors:

• family history and genetic factors (HLA-DR4)
• smoking, which also makes the disease more severe

Clinical features

• Symmetrical polyarthritis of the small joints of the hands (MCP and PIP joints) and feet (MTP joints). The distal interphalangeal joints are usually spared.
• Early morning stiffness lasting more than 30 minutes, often over an hour, improving with activity.
• Swollen, warm, tender joints.
• Fatigue and malaise.
• Late deformities:
  • ulnar deviation
  • swan-neck and boutonnière deformities
  • Z-thumb

Extra-articular features

• Rheumatoid nodules.
• Lungs: interstitial lung disease, pleural effusion and nodules.
• Eyes: dry eyes (secondary Sjögren's), scleritis and episcleritis.
• Blood: anaemia of chronic disease.
• Vessels: vasculitis.
• Heart: pericarditis and increased cardiovascular disease.
• Nerves: carpal tunnel syndrome, and atlantoaxial (C1–C2) instability, which is important before intubation.
• Felty's syndrome: RA with splenomegaly and neutropenia.

Investigations

• Rheumatoid factor (RF) — not specific; positive in other conditions and in some healthy people.
• Anti-CCP antibodies — highly specific; predict more erosive disease.
• ESR and CRP — raised in active disease.
• Full blood count — anaemia, raised platelets.
• X-rays of the hands and feet:
  • periarticular osteopenia
  • soft tissue swelling
  • joint space narrowing
  • erosions
• Ultrasound or MRI — detect early synovitis and erosions.

The 2010 ACR/EULAR classification criteria combine the number of joints involved, serology, acute-phase reactants and symptom duration.

Treatment

• Refer early to a rheumatologist when synovitis is suspected.
• Conventional DMARDs: methotrexate is first-line.
  • It is taken once weekly, with folic acid on another day.
  • It is teratogenic, so effective contraception is needed.
  • Monitor full blood count, liver function and kidney function.
  • Warn about mouth ulcers, infection and lung toxicity.
  Alternatives: sulfasalazine, leflunomide and hydroxychloroquine.
• Short courses of corticosteroids as a "bridge" while DMARDs start working.
• Biologic and targeted DMARDs (anti-TNF drugs, rituximab, tocilizumab, abatacept, JAK inhibitors) if conventional DMARDs fail. Screen for TB and hepatitis B first.
• NSAIDs for symptom relief, with gastroprotection where needed.
• Physiotherapy and occupational therapy.
• Stopping smoking.
• Cardiovascular risk management.
• Aim for remission or low disease activity ("treat to target"), using scores such as DAS28.

Exam pearls

• Rheumatoid arthritis spares the DIP joints. Osteoarthritis and psoriatic arthritis often involve them.
• Anti-CCP antibodies are more specific than rheumatoid factor.
• Methotrexate is taken once a week. Daily dosing errors can be fatal.

For more, see our Exam Night Notes 1.0: Rheumatology and the Medicine Companion.

Test yourself

5 exam-style single-best-answer questions. Choose your answer, then tap “Show answer”.

1. Which joints are typically spared in rheumatoid arthritis?

   1. Distal interphalangeal joints
   2. PIP joints
   3. MCP joints
   4. MTP joints
   5. Wrists
   Show answer

   Answer: A. Distal interphalangeal joints
   RA spares DIP joints; osteoarthritis and psoriatic arthritis often involve them.

2. Most specific antibody for rheumatoid arthritis:

   1. Anti-CCP
   2. Rheumatoid factor
   3. Anti-dsDNA
   4. ANCA
   5. ANA
   Show answer

   Answer: A. Anti-CCP
   Anti-CCP is highly specific and predicts erosive disease.

3. First-line conventional DMARD:

   1. Infliximab
   2. Colchicine
   3. Prednisolone
   4. Allopurinol
   5. Methotrexate
   Show answer

   Answer: E. Methotrexate
   Methotrexate, taken once weekly with folic acid, is first-line.

4. Before intubating a patient with long-standing RA, what should be considered?

   1. Atlantoaxial (C1–C2) instability
   2. Tracheal stenosis only
   3. Vocal cord nodules
   4. Dental caries
   5. Temporomandibular dislocation
   Show answer

   Answer: A. Atlantoaxial (C1–C2) instability
   Cervical spine instability can cause cord injury during neck extension.

5. X-ray finding typical of RA:

   1. Chondrocalcinosis
   2. Osteophytes
   3. Punched-out erosions with overhanging edges
   4. Pencil-in-cup deformity
   5. Periarticular osteopenia and erosions
   Show answer

   Answer: E. Periarticular osteopenia and erosions
   RA shows periarticular osteopenia, joint space narrowing and marginal erosions.

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Disclaimer

For education and exam preparation only. This is not medical advice and must not be used to diagnose or treat patients. Always follow current clinical guidelines and the advice of qualified senior colleagues.