About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Symmetrical inflammatory polyarthritis affecting small joints of hands and feet — morning stiffness >30 min
- Anti-CCP antibodies: most specific test (~97%). Rheumatoid factor: sensitive but not specific
- First-line DMARD: methotrexate (with folic acid). Start within 3 months of symptom onset
- Biologics (anti-TNF, rituximab, tocilizumab) if inadequate response to ≥2 conventional DMARDs
- Treat-to-target: aim for remission or low disease activity by 6 months. DAS28 score monitors response
Overview
Rheumatoid arthritis is a chronic systemic autoimmune disease primarily affecting the synovial joints. The hallmark is symmetrical inflammatory polyarthritis, particularly of the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints, with sparing of the DIP joints (unlike OA). Untreated, it leads to progressive joint destruction with erosions, deformity (swan-neck, boutonnière, ulnar deviation, Z-thumb), and disability. Extra-articular manifestations include rheumatoid nodules, interstitial lung disease, vasculitis, anaemia, and secondary Sjögren syndrome.
Epidemiology
RA affects approximately 1% of the UK population (400,000 people). Female:male ratio is 3:1. Peak onset is 40–60 years but can occur at any age. Genetic factors (HLA-DR4) and environmental triggers (smoking — strongest modifiable risk factor) interact. Smoking also reduces DMARD efficacy and worsens outcomes. Early diagnosis and treatment ("window of opportunity") dramatically improves long-term outcomes.
Clinical Features
Symptoms
Pain, swelling, and stiffness of small joints of hands and feet — symmetrical
Morning stiffness lasting >30 minutes (often >1 hour) — improves with activity
Fatigue and malaise
Gradual onset over weeks to months
Acute hot swollen joint — exclude septic arthritis
Signs
Boggy synovitis: soft tissue swelling of MCPs, PIPs, wrists, MTPs — symmetrical
Squeeze test positive (pain on compression of MCPs or MTPs)
Late deformities: swan-neck, boutonnière, ulnar deviation, Z-thumb, subluxation
Rheumatoid nodules (elbows, tendons — seropositive disease)
Cervical spine subluxation (atlantoaxial — risk of cord compression)
Investigations
First-line
Anti-CCP antibodiesMost specific test (~97% specificity). High titres predict erosive disease and worse prognosis
Rheumatoid factor (RF)Positive in ~70% RA but not specific — also positive in Sjögren, SLE, hepatitis C, and healthy elderly
Inflammatory markersCRP and ESR — elevated in active disease. Used for DAS28 calculation
FBCNormocytic anaemia of chronic disease, thrombocytosis (active inflammation)
Second-line
X-rays hands and feetEarly: soft tissue swelling, periarticular osteopenia. Late: joint space narrowing, erosions, subluxation
USS or MRI of affected jointsMore sensitive than X-ray for detecting early synovitis and erosions
Specialist
DAS28 scoreDisease Activity Score — combines tender/swollen joint count, ESR/CRP, patient global assessment. Guides treatment decisions
Cervical spine X-ray (flexion/extension)Pre-operatively if known RA — atlantoaxial subluxation risk during intubation
Management
NICE NG100 (Rheumatoid arthritis), 20181
First-line DMARDs — start within 3 months
- Methotrexate: first-line DMARD (oral or SC, typically 15–25 mg/week)
- Co-prescribe folic acid 5 mg (taken on a different day to methotrexate) to reduce side effects
- Monitor: FBC, LFTs every 2 weeks for 6 weeks, then monthly for 3 months, then 3-monthly
- Alternatives if methotrexate intolerant: leflunomide, sulfasalazine, hydroxychloroquine
2
Combination conventional DMARDs
- If monotherapy insufficient: combination (e.g. methotrexate + sulfasalazine + hydroxychloroquine — "triple therapy")
- Aim for treat-to-target: remission (DAS28 <2.6) or low disease activity by 6 months
3
Biologic DMARDs (if ≥2 conventional DMARDs failed)
- Anti-TNF: adalimumab, etanercept, infliximab, certolizumab, golimumab
- Other biologics: rituximab (anti-CD20), tocilizumab (anti-IL-6), abatacept (T-cell co-stimulation blocker)
- JAK inhibitors: tofacitinib, baricitinib — oral small molecules, alternative to biologics
- Screen for TB (CXR + IGRA) and hepatitis B/C before starting biologics
4
Adjunctive
- Bridging steroids: short courses (IM depomedrone or oral prednisolone) for flares while waiting for DMARD effect
- NSAIDs/COX-2 inhibitors: symptom relief (with PPI gastroprotection)
- Physiotherapy and occupational therapy
- Smoking cessation (improves DMARD response)
Complications
- Joint destruction and disability: Erosions, deformity, loss of function — the primary concern without early DMARD therapy
- Cervical spine subluxation: Atlantoaxial instability — can cause cord compression. Screen pre-operatively
- Cardiovascular disease: RA is an independent CVD risk factor — systemic inflammation accelerates atherosclerosis
- Interstitial lung disease: RA-ILD can be the presenting feature. Methotrexate can also cause pneumonitis
- Increased infection risk: From disease and immunosuppressive therapy (DMARDs, biologics, steroids)
- Secondary amyloidosis (AA): From chronic inflammation — causes nephrotic syndrome/renal failure
UKMLA Exam Tips
- 1RA = symmetrical small joint polyarthritis + morning stiffness >30 min + positive anti-CCP. Know this pattern
- 2Anti-CCP is MOST SPECIFIC. RF is LESS SPECIFIC (positive in many other conditions)
- 3Methotrexate: first-line DMARD. Co-prescribe FOLIC ACID. Monitor bloods. Teratogenic — pregnancy prevention
- 4DIP joint involvement = NOT RA — think osteoarthritis or psoriatic arthritis
- 5RA spares the DIP joints and the lumbar spine — classic negative examiner point
- 6Biologic DMARDs: screen for TB before starting anti-TNF therapy
- 7Felty syndrome: RA + splenomegaly + neutropenia — rare but classic exam question
practicetest your knowledge on rheumatoid arthritisApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — musculoskeletal and beyond.
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