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

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease causing persistent synovial inflammation, joint destruction, and disability. It affects approximately 1% of the global population — around 18 million people — and is three times more common in women than men, with peak onset between 40-60 years. Unlike osteoarthritis (wear-and-tear degeneration), RA results from immune-mediated attack on the synovium, leading to pannus formation, cartilage erosion, and bone destruction. Without effective treatment, RA causes progressive joint deformity — particularly the characteristic ulnar deviation of the fingers, swan-neck and boutonniere deformities — and significant disability within 2-3 years. Crucially, RA is also a systemic disease: it increases cardiovascular mortality by 50%, causes interstitial lung disease, accelerates osteoporosis, and contributes to anaemia, fatigue, and depression. Modern treat-to-target strategies using conventional and biologic DMARDs have dramatically improved outcomes.

RA results from a complex interplay of genetic and environmental factors. Genetic: HLA-DRB1 shared epitope alleles account for 30-40% of genetic risk; PTPN22, STAT4, and CTLA4 polymorphisms also contribute. The etiology involves loss of tolerance to citrullinated proteins — anti-citrullinated protein antibodies (ACPA/anti-CCP) appear years before clinical disease. Environmental triggers: cigarette smoking (strongest modifiable risk factor — increases RA risk 2-4x, especially in HLA-SE-positive individuals, and promotes ACPA production); periodontal disease (Porphyromonas gingivalis generates citrullinated proteins); gut microbiome dysbiosis; occupational silica dust exposure; and air pollution. Female sex and hormonal factors (postpartum, perimenopausal) modulate risk. Viral triggers (Epstein-Barr virus, CMV, HTLV) may initiate autoimmunity through molecular mimicry.

Early RA: bilateral symmetrical polyarthritis affecting small joints of the hands (MCPJs and PIPJs) and feet (MTPs), morning stiffness lasting more than 60 minutes (a hallmark feature distinguishing RA from osteoarthritis where stiffness resolves within 30 minutes), synovial swelling (boggy, warm joints), and grip weakness. Constitutional symptoms: fatigue (often severe and disabling), malaise, low-grade fever, and weight loss. Established RA: ulnar deviation of fingers, swan-neck and boutonniere deformities, wrist ankylosis, hallux valgus. Extra-articular manifestations: rheumatoid nodules (subcutaneous, pressure areas — 20-30% of seropositive patients), pulmonary disease (ILD, pleuritis), vasculitis, scleritis, Felty's syndrome (RA + splenomegaly + neutropaenia), and secondary Sjogren's syndrome (sicca symptoms). RA significantly increases the risk of cardiovascular disease, osteoporosis, lymphoma, and infection (especially with biologic therapy).

2010 ACR/EULAR classification criteria score: joints involved (0-5), serology (0-3), acute phase reactants (0-1), symptom duration (0-1) — score 6 or more classifies as RA. Serology: rheumatoid factor (RF) positive in 70-80% of RA; anti-CCP antibodies (ACPA) have higher specificity (95-97%) and predict erosive disease — positive years before symptoms. Acute phase reactants: elevated ESR and CRP reflect disease activity. FBC may show normocytic anaemia of chronic disease. Imaging: X-rays detect periarticular osteopaenia, joint space narrowing, and bony erosions (late features); MRI and musculoskeletal ultrasound detect synovitis and erosions at presentation before X-ray changes. DAS28 (Disease Activity Score 28 joints) quantifies disease activity using tender joint count, swollen joint count, ESR/CRP, and patient global assessment — guides treat-to-target management.

Treat-to-target (T2T): NICE and ACR/EULAR recommend aiming for DAS28 remission (DAS28 less than 2.6) or low disease activity (DAS28 less than 3.2) — assessed every 1-3 months until target achieved. Conventional synthetic DMARDs (csDMARDs): methotrexate (MTX) is the anchor first-line DMARD — 15-25 mg weekly (with folic acid 5 mg weekly to reduce toxicity); takes 4-6 weeks for onset; effective in 50-60%. Triple therapy (MTX + sulfasalazine + hydroxychloroquine) for inadequate MTX response. Biologic DMARDs (bDMARDs): TNF inhibitors (adalimumab, etanercept, certolizumab, golimumab, infliximab) — first-line biologics per NICE; IL-6 receptor inhibitors (tocilizumab, sarilumab) — effective for MTX-intolerant patients or high CRP; abatacept (CTLA4-Ig); rituximab (B-cell depletion — preferred in RF/ACPA-positive, previous malignancy, risk of reactivation infection). Targeted synthetic DMARDs (tsDMARDs): JAK inhibitors — baricitinib, tofacitinib, upadacitinib — oral, rapid onset; NICE approved for moderate-severe RA; black box warnings for VTE, MACE, malignancy. NSAIDs and glucocorticoids: short-term for symptomatic relief and bridging — minimize long-term use. Physiotherapy and occupational therapy optimise function.

Untreated RA causes progressive, irreversible joint destruction. Within 2-3 years, uncontrolled synovitis causes cartilage erosion, bone erosions visible on X-ray, and the characteristic deformities: ulnar deviation of the fingers, swan-neck (hyperextension PIP, flexion DIP) and boutonniere (flexion PIP, hyperextension DIP) deformities, Z-deformity of the thumb, and hallux valgus. Cervical spine involvement (atlantoaxial subluxation — C1-C2 instability) can cause spinal cord compression, myelopathy, and sudden death — an anaesthetic risk requiring preoperative assessment. Felty's syndrome (RA + splenomegaly + neutropaenia) causes recurrent serious infections. Rheumatoid vasculitis causes digital ischaemia, peripheral neuropathy, and skin ulceration. Interstitial lung disease (ILD) occurs in 10-15% of RA patients and can progress to respiratory failure — it is a significant cause of mortality. Cardiovascular mortality is increased 50% — equivalent to the risk of diabetes — due to accelerated atherosclerosis from systemic inflammation; myocardial infarction and stroke risk are substantially elevated in undertreated RA. Anaemia of chronic disease from persistent inflammation causes fatigue and reduced quality of life. Secondary osteoporosis from chronic inflammation and corticosteroid use significantly increases fracture risk. Without DMARDs, approximately 25-50% of RA patients become permanently work-disabled within 10 years.

There is no definitive prevention for RA, but smoking cessation is the single most important modifiable risk factor — stopping smoking reduces RA risk and improves treatment response in established disease. Periodontal hygiene may reduce risk. In established RA: tight treat-to-target control prevents joint damage and reduces cardiovascular mortality. Annual influenza and pneumococcal vaccination is essential (RA and immunosuppression increase infection risk). DEXA bone density monitoring with bisphosphonate prophylaxis for glucocorticoid use. Cardiovascular risk management: statins, blood pressure control (RA doubles CV risk). Regularly monitor FBC, LFTs, and renal function on MTX (monthly initially, then 3-monthly); screen for TB (IGRA) before biologics.

See a GP or seek urgent referral to a rheumatologist if you develop: persistent symmetrical joint swelling and stiffness lasting more than 6 weeks, especially involving small hand and foot joints; morning stiffness lasting more than 30-60 minutes; unexplained fatigue with joint symptoms. Seek urgent medical attention for: sudden hot, swollen single joint with fever — septic arthritis must be excluded; new neurological symptoms (cervical myelopathy from C1-C2 subluxation in advanced RA); unexplained breathlessness in known RA (ILD, pleuritis). If on biologic therapy: seek immediate medical advice for any fever, infection, or unusual symptoms — biologics suppress immune responses and can mask serious infections.