1. Definition and clinical relevance
Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory arthritis characterised by synovial proliferation, progressive joint destruction, and significant extra-articular disease burden. It affects roughly 1 in 100 Australians, with a female-to-male predominance of approximately 3:1, and onset most commonly occurring between ages 30 and 50. For an intern, RA matters because early recognition and prompt referral to rheumatology within three months of symptom onset can meaningfully alter the disease trajectory. Missing the diagnosis delays disease-modifying therapy and allows irreversible erosive damage to accumulate silently.
2. Key values, thresholds, scoring systems
2010 ACR/EULAR Classification Criteria (score 6 or above = definite RA)
| Domain | Category | Points |
|---|---|---|
| Joint involvement | One large joint (shoulder, elbow, hip, knee, ankle) | 0 |
| Two to ten large joints | 1 | |
| One to three medium or small joints (MCP, MTP, PIP, wrist) | 2 | |
| Four to ten medium or small joints | 3 | |
| More than ten joints, including at least one small joint | 5 | |
| Serology | Both RF and anti-CCP negative | 0 |
| Either RF or anti-CCP low positive (up to three times the upper limit of normal) | 2 | |
| Either RF or anti-CCP high positive (above three times the upper limit of normal) | 3 | |
| Acute-phase reactants | Both ESR and CRP within normal range | 0 |
| Either ESR or CRP elevated | 1 | |
| Symptom duration | Under six weeks | 0 |
| Six weeks or longer | 1 |
Serological and inflammatory markers
| Test | Sensitivity for RA | Specificity | Notes |
|---|---|---|---|
| IgM RF | ~70% | Moderate | Present in ~5% of healthy people; high titre predicts worse prognosis |
| Anti-CCP (ACPA) | ~70% | ~94% | Better predictor of progression from early inflammatory arthritis to persistent RA |
| RF + anti-CCP combined | Moderate | High | Together more specific than either alone |
| ESR | Non-specific | Low | Useful for monitoring disease activity |
| CRP | Non-specific | Low | Rises within 6 hours of inflammation; tracks disease activity closely |
Poor prognostic indicators
Persistently high RF titre, positive anti-CCP, elevated acute-phase reactants, involvement of many joints at presentation, early radiographic erosions, and extra-articular features all point toward a more aggressive disease course warranting earlier and more intensive DMARD therapy.
3. Approach: presentation and differential
History
The classic presentation (around 70% of cases) is a gradual, symmetrical peripheral polyarthritis evolving over weeks to months. Key features to elicit:
Early morning stiffness lasting more than one hour is a hallmark. Stiffness that improves with activity distinguishes inflammatory from mechanical joint disease. Pain, swelling, and functional loss predominantly affect the hands (MCPs, PIPs, wrists), feet (MTPs), and other peripheral joints. Fatigue and systemic malaise are common early symptoms.
Less common presentations include a rapid-onset explosive polyarthritis (more typical in older patients), palindromic attacks (monoarticular flares lasting 24 to 48 hours, with roughly half eventually progressing to persistent RA), a polymyalgia rheumatica-like picture in older adults, and a migratory pattern.
Red flags warranting urgent referral: small joint involvement of hands or feet, more than one joint affected, symptom duration already exceeding three months.
Examination findings
Hands: ulnar deviation of the fingers, Z-deformity of the thumb, swan-neck deformity (PIP hyperextension with DIP flexion), boutonniere deformity (PIP flexion with DIP hyperextension). Assess functional grip: power grip (lifting), precision grip (pen or key use), hook grip (carrying).
Feet: MTP joint swelling and tenderness, broadening of the forefoot, hammer-toe deformity.
Other joints: elbow fixed flexion deformity, shoulder painful arc, rotator cuff involvement in later disease.
Extra-articular features: subcutaneous rheumatoid nodules (elbows, pressure points), scleritis, sicca symptoms, interstitial lung disease, pericardial effusion, peripheral neuropathy, and vasculitis in severe disease.
Differential diagnosis (in order of clinical importance)
- Psoriatic arthritis (look for skin and nail changes)
- Osteoarthritis with nodal involvement (DIP involvement, Heberden nodes, less morning stiffness)
- Systemic lupus erythematosus (especially women under 50, check ANA, dsDNA)
- Polymyalgia rheumatica (age over 50, proximal girdle symptoms, normal joint examination)
- Reactive or post-viral arthritis (recent infection, asymmetric, often self-limiting)
- Septic arthritis (must exclude in any acutely hot swollen joint)
- Other connective tissue disorders (mixed connective tissue disease, Sjogren syndrome)
- Bilateral carpal tunnel syndrome (can mimic early hand RA)
4. Investigations
Bedside
Joint aspiration if septic arthritis cannot be excluded clinically. Synovial fluid in RA is typically turbid with elevated white cell count but sterile on culture.
Bloods
Full blood count: normochromic normocytic anaemia is typical; thrombocytosis may occur with active disease; leucopenia is less common. ESR and CRP: both usually elevated in active disease. RF (IgM): order as initial screen, but a positive result is non-specific. Anti-CCP antibodies: higher specificity (~94%) and should be ordered when RF is positive or RA is clinically suspected, as it largely supersedes RF as the confirmatory serological test. ANA: a minority of RA patients are weakly ANA-positive; a positive ANA should prompt consideration of SLE or overlap syndrome. Urea, electrolytes, creatinine, and LFTs: baseline before starting DMARDs. Fasting lipids and glucose: cardiovascular risk is substantially elevated in RA.
Imaging
Plain X-rays of hands and feet: may be normal early; periarticular osteoporosis and soft tissue swelling are early changes; later findings include joint space narrowing, marginal erosions, subluxation, and ankylosis.
MRI: detects synovitis and bone marrow oedema within the first three to six months of disease, well before erosions appear on plain X-ray. Useful when diagnosis is uncertain or to assess early damage.
Ultrasound: identifies synovitis and power Doppler signal indicating active inflammation; useful for guiding joint injections.
Chest X-ray: baseline before methotrexate; may reveal interstitial lung disease or pleural effusion.
5. Management
General principles
Refer all suspected RA to rheumatology promptly. A multidisciplinary approach is optimal: rheumatologist, GP, physiotherapist, occupational therapist, podiatrist, and nurse specialist. Screen for depression at diagnosis and ongoing reviews. Provide patient education about the disease course, treatment goals, and self-management strategies.
Analgesia and anti-inflammatory therapy
Paracetamol is first-line for pain. NSAIDs can reduce symptoms but do not alter disease progression; use the lowest effective dose given gastrointestinal and cardiovascular risks. Opioids should be avoided where possible.
Fish oil at a dose delivering approximately 4 g of omega-3 long-chain polyunsaturated fatty acids daily (roughly 0.2 g/kg) over several months has demonstrated modest anti-inflammatory benefit and may reduce NSAID requirements.
Glucocorticoids (oral prednisolone 10 mg daily, keeping below 15 mg daily where possible) are appropriate as a short-term bridge during DMARD initiation or for disease flares. Intra-articular depot corticosteroid injections are effective for isolated large joint flares.
Conventional synthetic DMARDs
Methotrexate (MTX) is the anchor drug for most patients with newly diagnosed RA and should be started as early as possible, ideally within three months of symptom onset.
Dosing: start at 5 to 10 mg orally once weekly on a fixed day each week. Titrate upward based on clinical response and tolerability to a maximum of 25 mg weekly; subcutaneous administration can be used if oral absorption is inadequate or gastrointestinal side effects are limiting.
Folic acid 5 to 10 mg twice weekly (not on the same day as MTX) is co-prescribed to reduce mucosal, haematological, and hepatic toxicity.
MTX monitoring
| Parameter | Timing |
|---|---|
| FBC, LFTs, creatinine | Baseline, then every 4 to 6 weeks for first 3 months, then every 3 months once stable |
| Chest X-ray | Baseline (screen for pre-existing lung disease) |
| Hepatitis B and C serology | Baseline (reactivation risk) |
| Pregnancy test | Before starting in women of childbearing age |
Withhold MTX and seek senior or rheumatology advice if: WCC falls below 3.5 x 10^9/L, neutrophils below 2.0 x 10^9/L, platelets below 150 x 10^9/L, ALT or AST rises above twice the upper limit of normal, or creatinine rises significantly. MTX is absolutely contraindicated in pregnancy and during breastfeeding; effective contraception is required during treatment and for at least three months after stopping.
Biological DMARDs (bDMARDs)
Consider if remission is not achieved with adequate conventional DMARD therapy (MTX monotherapy or combination regimens). All bDMARDs are more effective when combined with MTX. Never use two biological agents concurrently.
Classes include TNF inhibitors (most commonly used first-line biologic), IL-6 inhibitors, T-cell co-stimulation blockers, and B-cell depleting agents. JAK inhibitors (targeted synthetic DMARDs) are an oral alternative.
Infection risk is substantially elevated on bDMARDs, particularly atypical pneumonias, tuberculosis, and listeriosis. Screen for latent TB before starting. All patients must report any unexpected fever or new symptoms promptly.
Vaccinations: pneumococcal, influenza, hepatitis A and B, and HPV vaccines are recommended before or during DMARD therapy. Avoid live vaccines once on immunosuppression.
Disposition and escalation
Any acutely hot, swollen joint in a patient on DMARDs requires urgent joint aspiration to exclude septic arthritis before attributing the flare to RA. Involve the rheumatology team early. Patients with systemic complications (vasculitis, interstitial lung disease, scleritis) require urgent specialist input.
6. Australian-specific considerations
Aboriginal and Torres Strait Islander peoples experience higher rates of inflammatory arthritis and face significant barriers to specialist access, particularly in remote and regional areas. When assessing joint disease in this population, consider that reactive arthritis following streptococcal or other infections may be more prevalent, and that rheumatic fever must be excluded in younger patients with polyarthritis. Cultural safety in the consultation, including involving family members and community health workers where appropriate, improves engagement with the often complex and long-term treatment plans required for RA.
Rural and remote patients face delays in rheumatology review; telehealth rheumatology services are available in most states and should be arranged early rather than waiting for in-person appointments. GP management plans (MBS item 721) and team care arrangements (item 723) are appropriate for coordinating the multidisciplinary care RA requires, including physiotherapy and occupational therapy. Chronic disease management plans also facilitate allied health Medicare rebates.
MTX requires reliable pathology access for monitoring; in very remote settings, confirm that the patient can access regular blood tests before initiating therapy, and arrange a clear monitoring and recall system.
Mandatory reporting obligations may arise if RA-related disability affects a patient's capacity to drive safely; assess functional hand and foot involvement and advise accordingly.
Clinical pearls
- Anti-CCP antibodies have approximately 94% specificity for RA, far exceeding RF, and when both are positive together the diagnosis is highly likely; a positive RF alone is non-specific and found in around 5% of healthy individuals.
- Bone erosions detectable on MRI can appear within the first three to six months of disease, well before plain X-ray changes emerge, which is the biological rationale for starting DMARDs as early as possible.
- MTX is given once weekly, not daily; a prescribing error resulting in daily dosing is potentially fatal and is a well-recognised medication safety event.
- Folic acid must be co-prescribed with MTX but should not be taken on the same day as the MTX dose, as it reduces toxicity without blunting efficacy.
- Any acutely inflamed joint in a patient with known RA must have septic arthritis excluded by aspiration before assuming it is a disease flare, as immunosuppression masks the typical signs of infection.
- Cardiovascular risk is substantially elevated in RA independent of traditional risk factors; lipids, blood pressure, and smoking status should be addressed actively at every review.