Rheumatoid arthritis
Exam Tips
- In UK exams, the key action is early referral: do not wait for RF/anti-CCP or inflammatory markers if persistent synovitis is clinically present.
- Classic distribution is symmetrical MCP/PIP/MTP inflammation with prolonged morning stiffness; DIP involvement suggests alternative diagnoses (for example psoriatic or osteoarthritis).
- A positive MCP squeeze test and inability to make a fist are high-yield bedside clues to inflammatory synovitis.
- Normal ESR/CRP does not exclude RA, especially early disease.
- Anti-CCP positivity is more specific than RF and predicts erosive disease in exam stems.
- Before specialist review, use short-term NSAID plus PPI if appropriate, and avoid starting glucocorticoids in primary care for undiagnosed suspected RA.
- Always mention cardiovascular risk and osteoporosis prevention when discussing long-term RA management.
Definition
Rheumatoid arthritis is a chronic, systemic autoimmune inflammatory arthritis that classically causes persistent, symmetrical synovitis of small joints (especially MCP, PIP, and MTP joints) with prolonged morning stiffness. It is a clinical diagnosis supported by serology and imaging, and early untreated disease can progress to erosive joint destruction, extra-articular organ involvement, disability, and increased cardiovascular mortality.
Pathophysiology
In genetically susceptible people (notably HLA-DRB1 shared-epitope alleles), environmental triggers such as cigarette smoke promote loss of immune tolerance to citrullinated self-proteins. Autoantibodies (anti-CCP and rheumatoid factor) and immune complexes drive synovial inflammation via TNF-alpha, IL-6, and IL-1, causing hyperplastic synovium (pannus), cartilage damage, and osteoclast-mediated bone erosion through RANKL signalling. Persistent cytokine activity also explains systemic features (fatigue, anaemia, weight loss) and extra-articular disease (lung, eye, vasculitic, cardiovascular). See figure reference: classic pannus-erosion pathway and joint-space loss diagrams in standard rheumatology pathology chapters.
Risk Factors
- Female sex (about 2-4 times more common than in men)
- Increasing age (can occur at any age; incidence peak in older adults)
- First-degree family history of rheumatoid arthritis (approximately 2-4-fold increased risk)
- Cigarette smoking
- Genetic susceptibility (for example HLA-DRB1 shared epitope)
- Pre-existing autoimmunity/seropositivity (anti-CCP positivity predicts persistent erosive disease)
Clinical Features
Symptoms
- Insidious onset joint pain, often worse after rest/inactivity
- Prolonged early morning stiffness, typically more than 60 minutes
- Symmetrical small-joint symptoms in hands/feet (MCP, PIP, MTP), though any synovial joint may be involved
- Functional difficulty such as reduced grip or inability to make a fist
- Systemic symptoms: fatigue, malaise, low-grade fever, sweats, weight loss
- Possible relapsing-remitting (palindromic) early course in some patients
Signs
- Boggy, warm, tender synovial swelling around joints (not bony enlargement)
- Symmetrical synovitis with MCP/PIP/MTP involvement; DIP joints usually spared
- Positive MCP/MTP squeeze test
- Reduced range of motion and reduced grip strength
- Rheumatoid nodules over extensor surfaces
- Extra-articular signs in severe disease (for example dry eyes, pleuro-pulmonary signs, vasculitic skin lesions)
Investigations
Management
Lifestyle Modifications
- Urgent early rheumatology referral for persistent synovitis (target specialist review within 3 weeks; urgent 3 working days if small joints affected, multiple joints affected, or symptom delay at least 3 months)
- Smoking cessation (reduces inflammatory burden and cardiovascular risk)
- Physiotherapy and occupational therapy: joint protection, hand exercises, splints, function preservation
- Regular cardiovascular risk assessment and management (accelerated atherosclerosis risk)
- Bone health strategy where indicated (calcium/vitamin D, fracture risk assessment, exercise)
- Vaccination review before immunosuppression (influenza, pneumococcal, others as appropriate)
Pharmacological Treatment
Symptom control while awaiting specialist assessment
- Ibuprofen 400 mg three times daily (usual anti-inflammatory range up to 2.4 g/day in divided doses)
- Naproxen 500 mg twice daily
- Diclofenac 50 mg three times daily or modified-release 75 mg twice daily
- Celecoxib 100 mg twice daily or 200 mg once daily
- Etoricoxib 60 mg once daily
- Omeprazole 20 mg once daily (PPI gastroprotection with NSAID/coxib)
Use lowest effective NSAID dose for shortest duration. Check GI, renal, hepatic, and cardiovascular risk; avoid/limit in pregnancy (especially third trimester), CKD, peptic ulcer disease, heart failure, and uncontrolled hypertension. In suspected RA, do not start oral glucocorticoids in primary care before specialist assessment because this may mask disease features.
Conventional synthetic DMARDs (usually specialist-initiated early, often in combination)
- Methotrexate 7.5-15 mg ONCE weekly orally/subcutaneously, titrated (commonly up to 20-25 mg once weekly) plus folic acid 5 mg once weekly on a different day
- Sulfasalazine up to 1 g twice daily (titrated from lower starting dose)
- Hydroxychloroquine 200-400 mg daily (do not exceed 5 mg/kg/day actual body weight for retinal safety)
- Leflunomide 10-20 mg once daily
Methotrexate is teratogenic and must be prescribed weekly (never daily); requires regular FBC, LFT, and renal monitoring and caution with infection, liver disease, and excess alcohol. Sulfasalazine can cause cytopenias/hepatotoxicity and is contraindicated in sulfonamide/salicylate hypersensitivity. Hydroxychloroquine requires baseline and ongoing retinal toxicity surveillance. Leflunomide is teratogenic with long half-life; washout may be required for pregnancy planning.
Biologic and targeted synthetic DMARDs for inadequate response (specialist care)
- Adalimumab 40 mg subcutaneously every 2 weeks
- Etanercept 50 mg subcutaneously once weekly
- Tocilizumab (for example 162 mg subcutaneously weekly or every 2 weeks depending on regimen)
- Abatacept, rituximab, or JAK inhibitors such as baricitinib 4 mg once daily (regimen individualized)
Screen for TB, hepatitis B/C, and other infection risks before biologics/JAK inhibitors; avoid starting during active serious infection. Counsel regarding sepsis risk, herpes zoster risk (especially with JAK inhibitors), malignancy/skin cancer surveillance, and thrombosis warnings where relevant.
Glucocorticoids (specialist-directed adjunct or flare control)
- Intra-articular triamcinolone injection (joint-specific dose per specialist)
- Short oral prednisolone course (for example 5-15 mg daily, taper plan individualized)
Use the minimum effective dose and duration due to osteoporosis, diabetes, hypertension, mood effects, and infection risk; provide bone protection when prolonged courses are needed.
Surgical / Interventional
- Synovectomy for persistent localized synovitis
- Tendon repair for tendon rupture
- Carpal tunnel decompression when indicated
- Joint replacement (for example MCP, wrist, hip, knee) in end-stage destructive disease
- Cervical spine decompression/stabilization in cervical myelopathy or instability
Complications
- Erosive joint destruction, deformity, and functional disability
- Carpal tunnel syndrome and tendon rupture
- Cervical spine instability/myelopathy
- Interstitial lung disease, pleural effusion, fibrosing alveolitis
- Dry eye syndrome and peripheral ulcerative keratitis
- Rheumatoid nodules and vasculitis (including ulceration)
- Anaemia and fatigue
- Felty syndrome (splenomegaly with neutropenia, uncommon)
- Accelerated atherosclerotic cardiovascular disease (major cause of excess mortality)
- Pericardial involvement (often subclinical)
- Lymphoma risk approximately doubled
- Serious infections related to disease and immunosuppression
- Drug-related harms: NSAID GI/renal/cardiovascular toxicity, methotrexate hepatotoxicity/cytopenias, steroid-induced osteoporosis/fracture
Prognosis
Prognosis is highly variable but is markedly improved by rapid recognition and early treat-to-target DMARD therapy. Poorer outcomes are associated with delayed presentation, high joint count, persistent active synovitis, early erosions, seropositivity (especially anti-CCP), and extra-articular disease; without control, RA increases disability and premature mortality, particularly through cardiovascular disease. In functional terms, work loss is common early in disease course if inflammation is not promptly controlled.
Sources & References
🏥BMJ Best Practice(3)
✅NICE Guidelines(1)
- Rheumatoid arthritis[overview]