Rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune disease that primarily targets synovial joints, leading to persistent inflammation, pain, and progressive structural damage. Although the condition chiefly affects the musculoskeletal system, it is also a systemic disorder capable of involving multiple organs. Symptoms may begin subtly over weeks or months and typically worsen without appropriate management. The disorder is more common in women than men and usually presents in middle adulthood.

Clinical Features and Systemic Manifestations

Rheumatoid arthritis most often affects the small joints of the hands, feet, and wrists. Inflammatory synovitis leads to swelling, warmth, tenderness, and stiffness, which is characteristically worse following periods of rest and particularly severe on waking. Morning stiffness lasting longer than an hour is a hallmark differentiating rheumatoid arthritis from non-inflammatory joint disease.
The joint involvement frequently follows a symmetrical pattern, although asymmetry may be observed early in the disease. Progressive synovial proliferation and inflammation can lead to tendon tethering, cartilage damage and bone erosion. These changes impair range of movement and can lead to marked deformity. Common deformities include ulnar deviation of the fingers, boutonnière deformity, swan-neck deformity and the Z-thumb pattern. Severe long-standing cases may progress to arthritis mutilans.
About one quarter of individuals develop extra-articular features. The skin may show rheumatoid nodules, which are necrotising granulomatous lesions typically located over pressure points such as the olecranon or metacarpophalangeal joints. These nodules are associated with seropositivity for rheumatoid factor or anti-cyclic citrullinated peptide antibodies and with severe erosive disease. Less common cutaneous manifestations include vasculitis, ulcers, erythema nodosum and skin fragility, the latter often exacerbated by corticosteroid use.
Pulmonary involvement is relatively frequent and may include interstitial lung disease, pleural effusion and, in individuals with coal dust exposure, Caplan’s syndrome. Cardiovascular complications are prominent and carry significant morbidity. People with rheumatoid arthritis exhibit increased risks of atherosclerosis, myocardial infarction, cerebrovascular events and pericardial inflammation. Optimal control of systemic inflammation alongside conventional cardiovascular risk management is crucial.
Hematological abnormalities are common, with anaemia of chronic disease being the most prevalent. This results from inflammation-induced disturbances in iron metabolism, particularly elevated hepcidin levels which sequester iron in storage sites. Other complications include mood disorders, fatigue, increased infection risk, osteoporosis and involvement of the nervous system, such as mononeuritis multiplex in the context of vasculitis.

Aetiology and Pathogenesis

The precise cause of rheumatoid arthritis remains unknown, but its development reflects the interplay of genetic predisposition and environmental triggers. Individuals who carry certain HLA-DRB1 alleles, particularly those encoding the ‘shared epitope’, have increased susceptibility. Environmental factors such as smoking are well-established contributors, potentially through citrullination of proteins that promote autoimmune reactivity.
The disease process begins when the immune system mistakenly identifies components of the synovial membrane as targets. Activated T cells, B cells, macrophages and fibroblast-like synoviocytes play central roles in sustaining inflammation. These cell populations produce cytokines including tumour necrosis factor, interleukin-1 and interleukin-6, all of which drive synovial proliferation, recruitment of further inflammatory cells and destruction of cartilage and bone.
Fibroblast-like synoviocytes, specialised mesenchymal cells in the synovium, are particularly important in driving joint destruction. Their invasive behaviour contributes to pannus formation, cartilage degradation and bone erosion. The persistent inflammatory milieu also promotes angiogenesis, further facilitating synovial expansion.

Diagnosis

Diagnosis is primarily clinical, relying on characteristic symptoms and patterns of joint involvement. Clinical assessment is supplemented by laboratory tests and imaging techniques to support the diagnosis and exclude alternative conditions. Serological markers include rheumatoid factor and anti-cyclic citrullinated peptide antibodies, both of which increase diagnostic confidence and correlate with disease severity.
Imaging modalities such as ultrasonic examination, radiography or magnetic resonance imaging may reveal synovitis, joint space narrowing and early erosions. Differential diagnosis includes systemic lupus erythematosus, psoriatic arthritis, fibromyalgia and other inflammatory or degenerative joint diseases.

Management Strategies

Management aims to reduce pain, suppress inflammation and preserve joint function. A combination of non-pharmacological and pharmacological interventions is generally required.
Non-pharmacological measures include balanced rest and exercise programmes, physiotherapy, occupational therapy, orthotic support and assistive devices. Patient education and lifestyle modification, including smoking cessation and cardiovascular risk reduction, are essential components of long-term care.
Analgesics, non-steroidal anti-inflammatory drugs and short courses of glucocorticoids provide symptomatic relief. Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate and hydroxychloroquine form the cornerstone of treatment, targeting underlying immune processes to slow disease progression. In cases where response to conventional DMARDs is inadequate, biological agents that inhibit cytokines or deplete specific immune cell populations may be introduced, although these therapies carry increased risks of infection and other adverse effects.
Surgical intervention, including joint replacement or arthrodesis, may be appropriate for individuals with severe structural damage or persistent pain unresponsive to medical therapy.

Epidemiology and Historical Background

Rheumatoid arthritis affects approximately 0.5% of adults in developed countries, with annual incidence rates ranging from 5 to 50 per 100,000 individuals. Women are affected two to three times more often than men. Onset typically occurs in middle age, but the condition can develop at any stage of life. Mortality associated with rheumatoid arthritis has risen modestly over recent decades, largely due to increased recognition of cardiovascular and systemic complications.
The first formal description of the disease was recorded in 1800 by Augustin Jacob Landré-Beauvais of Paris. The term “rheumatoid arthritis” combines Greek roots meaning “watery” and “inflamed joints”, reflecting its characteristic clinical features. The modern understanding of rheumatoid arthritis continues to evolve, with ongoing research exploring the immunological mechanisms, genetic influences and optimal therapeutic approaches for this complex autoimmune condition.