Rheumatoid Arthritis

Rheumatoid Arthritis affects approximately 1% of the UK population, with a 3:1 female-to-male ratio and a peak onset between ages 30 and 50. It typically presents as a symmetrical, peripheral polyarthritis affecting the small joints of the hands (MCP, PIP) and feet (MTP). Unlike OA, RA involves significant morning stiffness lasting over an hour and improves with activity. Extra-articular manifestations are common and include rheumatoid nodules, vasculitis, episcleritis, and interstitial lung disease. Diagnosis is based on the 2010 ACR/EULAR criteria, which consider joint involvement, serology (RF and anti-CCP), acute phase reactants (CRP/ESR), and duration of symptoms. Anti-CCP (cyclic citrullinated peptide) antibodies are highly specific for RA and often predictive of more aggressive erosive disease. Management has been revolutionised by Biological DMARDs, but the cornerstone remains conventional synthetic DMARDs (csDMARDs) like Methotrexate. The 'treat-to-target' strategy aims for clinical remission or low disease activity through frequent monitoring and escalation of therapy.

RA is driven by an auto-immune response in genetically susceptible individuals (linked to the HLA-DRB1 'shared epitope'). Environmental triggers, most notably cigarette smoking and certain oral bacteria (P. gingivalis), lead to the post-translational modification of proteins (citrullination). In RA, the immune system loses tolerance to these citrullinated proteins, leading to the production of anti-CCP antibodies. The primary site of pathology is the synovium, which undergoes hyperplastic growth (forming a 'pannus'). This pannus is rich in inflammatory cells (T-cells, B-cells, macrophages) and secretes cytokines like TNF-alpha, IL-1, and IL-6. These cytokines stimulate osteoclast activity and protease production, which leads to the hallmark marginal erosions of bone and destruction of articular cartilage.

Presentation is typically a subacute onset of pain, swelling, and stiffness in the hands and feet. Late-stage deformities include 'Z-deformity' of the thumb, ulnar deviation of the MCPJs, swan-neck deformity, and boutonniere deformity. Systemic features include malaise, weight loss, and low-grade fever. Extra-articular features: Rheumatoid nodules (extensor surfaces), pulmonary fibrosis, pleural effusions, Felty’s syndrome (RA + Splenomegaly + Neutropenia), and scleritis. Atlanto-axial subluxation is a critical complication; patients requiring intubation must have cervical spine X-rays to assess for instability. Patients have a significantly higher risk of ischaemic heart disease due to accelerated atherosclerosis.

- Bloods: Rheumatoid Factor (sensitive but not specific), Anti-CCP (highly specific), ESR/CRP (markers of activity), FBC (anaemia of chronic disease).
- Imaging: Hand and feet X-rays (even if asymptomatic) to look for joint space narrowing, peri-articular osteopenia, and marginal erosions. Ultrasound is increasingly used to detect subclinical synovitis.
- Special: Synovial fluid analysis (inflammatory: high WBC, no crystals).

NICE NG100 guidelines: Referral to rheumatology should be urgent (within 3 weeks) for any suspected persistent synovitis. Medical: First-line is DMARD monotherapy (usually Methotrexate, alternatives: Sulfasalazine, Leflunomide) with bridging glucocorticoids (oral, IM, or IA) to provide rapid symptomatic relief. If target (remission) is not met, combinations of csDMARDs are used. Biological DMARDs (e.g., TNF-inhibitors like Adalimumab/Etanercept, or B-cell depletion like Rituximab) are used if csDMARDs fail and DAS28 score is >5.1 (some newer guidelines allow for >3.2). Surgical: Joint replacement, synovectomy, or tendon repair.