Rheumatoid Arthritis — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that primarily targets synovial joints, causing progressive joint inflammation, destruction, disability, and extra-articular complications. It affects approximately 1% of the global adult population — approximately 18 million people — with a female predominance of 2-3:1. RA typically begins between ages 40-60 but can occur at any age. Unlike osteoarthritis (a degenerative condition), RA is driven by autoimmune activation of synovial T cells and B cells producing rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP) that drive synovial inflammation, pannus (inflammatory tissue) formation, and ultimately cartilage erosion and bone destruction. The 'treat-to-target' paradigm — aiming for clinical remission or low disease activity — has transformed outcomes in modern RA management. Timely initiation of disease-modifying therapy (methotrexate or biologic agents within 3-6 months of symptom onset) dramatically alters long-term outcomes and prevents joint destruction.

RA is a multifactorial disease with genetic and environmental components. Genetic factors: HLA-DRB1 alleles (particularly the 'shared epitope' — HLA-DRB1*04:01, *04:04, *01:01) account for 40-50% of genetic risk, especially for seropositive RA (RF/ACPA-positive). PTPN22 and other immune regulatory gene variants also contribute. Environmental risk factors: cigarette smoking is the strongest environmental risk factor (doubles RA risk, particularly in HLA-DR4 carriers; also worsens disease and reduces biologic response); occupational silica dust exposure; air pollution; periodontal disease (Porphyromonas gingivalis produces citrullinated proteins triggering ACPA formation). Hormonal influences: RA frequently remits during pregnancy and flares postpartum, suggesting oestrogen and prolactin roles. Gut microbiome dysbiosis has been implicated in early RA pathogenesis.

RA typically presents with symmetrical polyarthritis affecting small joints of the hands (metacarpophalangeal and proximal interphalangeal joints) and feet (metatarsophalangeal joints), wrists, and knees. Key features distinguishing RA from osteoarthritis: prolonged morning stiffness (over 45 minutes — a hallmark of inflammatory arthritis), symmetrical involvement, soft-tissue swelling around joints (synovitis), and absence of distal interphalangeal joint involvement. Examination reveals warm, tender, swollen joints with reduced grip strength; later — ulnar deviation of fingers, swan-neck and boutonniere deformities, and volar subluxation at the MCP joints. Extra-articular manifestations: rheumatoid nodules (firm subcutaneous nodules, 20-30%), rheumatoid vasculitis (skin, digital ischaemia), interstitial lung disease (10-30%), pericarditis, episcleritis, secondary Sjogren's syndrome, and Felty's syndrome (RA + splenomegaly + leucopenia). Constitutional symptoms include fatigue, low-grade fever, and weight loss.

Diagnosis uses the 2010 ACR/EULAR classification criteria (scoring system for definite RA requiring 6 or more points): joint involvement, serology (RF, ACPA), acute-phase reactants (CRP, ESR), and symptom duration. Serology: ACPA (anti-CCP antibodies) — most specific marker for RA (specificity 95-98%); present 5-10 years before symptoms; associated with more erosive disease. Rheumatoid factor (RF) — positive in 70-80% of RA but also in Sjogren's, hepatitis C, and healthy elderly (less specific). Acute-phase reactants: elevated CRP and ESR confirm active inflammation but are non-specific. Imaging: plain X-rays — early changes are soft-tissue swelling and periarticular osteopaenia; erosions (juxta-articular cortical bone defects) are specific for inflammatory arthritis; MRI and ultrasound detect early synovitis and erosions before X-ray changes. Differential diagnoses include psoriatic arthritis (DIP involvement, nail disease, asymmetric), systemic lupus (anti-dsDNA positive, Jaccoud's non-erosive arthritis), reactive arthritis, gout, and seronegative spondyloarthropathy.

The treat-to-target strategy aims for clinical remission (DAS28 below 2.6) or low disease activity, with monthly reassessment and treatment escalation until target is achieved. Conventional synthetic DMARDs (csDMARDs) — first-line: methotrexate (MTX) 15-25 mg weekly with folic acid 5 mg weekly — the anchor drug for RA; effective in 40-60%; requires monitoring of FBC, LFTs, and creatinine (hepatotoxicity, cytopaenia, and pneumonitis risks); avoid in pregnancy; combination csDMARD therapy (MTX + hydroxychloroquine + sulfasalazine — triple therapy) is more effective than monotherapy. Biologic DMARDs (bDMARDs) for inadequate MTX response: anti-TNF agents (adalimumab, etanercept, infliximab, certolizumab, golimumab) — first-line biologics; screen for latent TB and hepatitis B before starting. IL-6 inhibitors (tocilizumab, sarilumab) — effective for systemic features. Abatacept (CTLA4-Ig, T-cell costimulation inhibitor). JAK inhibitors (tofacitinib, baricitinib, upadacitinib) — targeted synthetic DMARDs (tsDMARDs); oral; highly effective but increased risk of venous thromboembolism and infections (use cautiously in cardiovascular risk). Rituximab (anti-CD20, B-cell depletion) — preferred in concurrent malignancy history. NSAIDs and corticosteroids provide bridging anti-inflammatory relief; avoid long-term corticosteroids due to metabolic and bone complications.

Uncontrolled RA causes irreversible joint destruction — bone erosions develop within 2 years in 60-70% of patients without adequate treatment. Cardiovascular mortality is doubled in RA from chronic systemic inflammation accelerating atherosclerosis. Interstitial lung disease (ILD) affects 10-20% of RA patients and is a leading cause of disease-related death. Sicca syndrome (secondary Sjögren's — dry eyes and mouth) affects 15-30%. Atlanto-axial instability from C1-C2 erosions can cause spinal cord compression. Infection risk is 3-5 times higher from both the disease and immunosuppressive treatment. Lymphoma risk is elevated 2-3 fold. Achieving remission within 6 months of symptom onset (treat-to-target strategy) prevents most irreversible structural damage.

Smoking cessation is the most important preventive and management measure — smoking doubles RA risk, worsens disease activity and radiographic progression, and reduces response to biologic therapy. Regular aerobic exercise and resistance training are safe and beneficial in RA — reducing cardiovascular risk (the leading cause of excess mortality), maintaining muscle strength, and improving quality of life; evidence-based exercise does not worsen RA. Maintain a healthy BMI — obesity worsens RA activity, increases cardiovascular risk, and reduces biologic therapy response. Oral health: treat periodontal disease, which is linked to RA through shared pathogenic mechanisms. Vaccinations are essential before starting immunosuppressive therapy — pneumococcal (PPSV23), influenza (annual), herpes zoster, and hepatitis B. Patients on immunosuppressants should avoid live vaccines. Osteoporosis prevention: calcium 1,000-1,200 mg/day and vitamin D 800-1,000 IU/day plus bisphosphonates for those on long-term corticosteroids.

See a GP promptly if you have persistent symmetric joint pain and swelling lasting more than 6 weeks, especially with morning stiffness over 30 minutes — early referral to a rheumatologist within 3 months significantly improves long-term outcomes. RA is a medical emergency in the 'window of opportunity' — early aggressive treatment before bone erosion prevents irreversible joint destruction. Seek urgent rheumatology review if: acute worsening (flare) on current therapy, signs of extra-articular complications (breathlessness suggesting ILD, eye redness, skin ulcers), or systemic symptoms (fever, weight loss — exclude infection or malignancy). Patients on MTX or biologics should seek urgent medical care for fever, persistent sore throat, or mouth ulcers (potential agranulocytosis or serious infection). Any breathlessness on MTX warrants same-day evaluation to exclude MTX-induced pneumonitis.