Introduction
It affects the lining of the joints, causing an inflammatory response that may also involve
other tissues and organs, such as the lungs, heart, and eyes.
RA is a progressive disease with no known cure but can be managed effectively through
early diagnosis and treatment.
The exact cause of RA remains unclear; however, genetic predisposition (e.g., HLA-DR4
gene) and environmental factors (e.g., smoking) are recognized contributors.
A significantly impacts the quality of life, limiting mobility and daily activities if left untreated.
Incidence and Prevalence
Global prevalence: RA affects approximately 0.5-1% of the global population.
Gender distribution: Women are 2-3 times more likely to develop RA compared to men.
Age of onset: Commonly diagnosed between 30 and 60 years of age, though juvenile forms can occur in
children under 16.
Geographical variation: Higher prevalence in developed countries, particularly in urban settings.
Indigenous populations like Native Americans exhibit significantly higher rates.
Risk factors: Genetic predisposition (e.g., HLA-DR4 allele), smoking, obesity, and environmental triggers.
Defination
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily affects synovial joints.
It is characterized by inflammation, pain, stiffness, and progressive joint destruction.
RA occurs when the immune system mistakenly attacks healthy tissues, leading to joint damage and, in
some cases, systemic complications.
The disease is known for its symmetrical joint involvement and potential to cause deformities and disability.
Aetiology/risk factors
• Genetic Factors:- A genetic predisposition is evident, particularly with the HLA-DR4 gene, which
increases susceptibility.
• Immune System Dysfunction:- RA involves an autoimmune response where the immune system attacks
the synovial membranes, producing rheumatoid factor (RF) and inflammatory cytokines like TNF-α and
• IL-1.
Envormental Factor s:- Infections (e.g., Epstein-Barr virus) and smoking are significant triggers,
especially in genetically predisposed individuals.
• Hormonal Factors:- More common in women, suggesting a hormonal link, with estrogen possibly
contributing to susceptibility.
• Age:- RA typically affects individuals aged 30-60 years, though it can occur at any age.
• Psychological Factors:- Stress can exacerbate RA by increasing inflammatory markers.
Risk Factors for
Rheumatoid Arthritis
(RA)
• Gender:- Women are more likely to develop RA than men.
• Smoking:- A significant modifiable risk factor, especially in
genetically predisposed individuals.
• Obesity:- Increases the risk of developing RA and can
worsen disease severity.
• Other Autoimmune Dis- Higher risk in individuals with
conditions like Hashimoto’s thyroiditis or systemic lupus
erythematosus (SLE).
Types of Rheumatoid Arthritis
• Seropositive Rheumatoid Arthritis:- Defined by the presence of rheumatoid factor (RF) or anti-
citrullinated protein antibodies (ACPA) in the blood.- Often associated with more severe symptoms and
extra-articular manifestations, such as rheumatoid nodules and vasculitis.
• Seronegative Rheumatoid Arthritis:- Absence of RF and ACPA in blood tests but diagnosed based on
clinical symptoms and imaging findings.- Typically presents with less severe joint involvement
compared to seropositive RA.
• Juvenile Idiopathic Arthritis (JIA):- Onset occurs before the age of 16, affecting children and
adolescents.- Subtypes include oligoarticular (fewer than five joints affected), polyarticular (more than
five joints affected), and systemic (associated with fever and rash).
• Palindromic Rheumatism:- Characterized by recurrent episodes of joint inflammation that resolve
completely without causing permanent damage.- May progress to classical rheumatoid arthritis over
time.
Pathophysiology
Immune System Activation
Activation of T lymphocytes and production of inflammatory cytokines (TNF-α, IL-1, IL-6)
Synovial Inflammation (Synovitis)
Formation of Pannus (abnormal tissue)
Pannus invades cartilage and bone, leading to joint destruction
Articular Damage (joint deformities and loss of function)
Systemic Involvement (extra-articular manifestations: rheumatoid nodules, vasculitis, lung disease)
Presence of Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (ACPA)
Immune Complexes cause further tissue damage
Clinical Manifestations
Articular Manifestations:
• Pain and Tenderness: Persistent pain and tenderness in affected joints, especially small joints like fingers, wrists, and toes.
• Morning Stiffness: Lasting more than 30 minutes, typically improving with movement.
• Swelling and Warmth: Symmetrical joint swelling, with joints feeling warm and spongy.
• Deformities:
• Swan-neck deformity: Hyperextension of PIP (Proximal Interphalangeal) joints and flexion of DIP (Distal Interphalangeal) joints.
• Boutonnière deformity: Flexion of PIP and hyperextension of DIP joints.
• Ulnar Deviation: Fingers shift toward the ulnar side of the hand.
• Reduced Mobility: Limited range of motion and difficulty performing daily activities.
Systemic Manifestations:
• Fatigue: Severe tiredness that worsens with disease activity.
• Low-grade Fever: Indicates ongoing systemic inflammation.
• Weight Loss: Due to chronic inflammation and reduced appetite.
• General Malaise: A feeling of unease and discomfort.
Extra-Articular Manifestations:
• Rheumatoid Nodules: Hard lumps under the skin, commonly over pressure points like elbows and fingers.
• Pulmonary Involvement: Interstitial lung disease, pleuritis, or pulmonary nodules.
• Cardiovascular Complications: Pericarditis, myocarditis, and increased risk of atherosclerosis.
• Ocular Involvement: Dry eyes, episcleritis, scleritis, or keratoconjunctivitis sicca (Sjogren’s syndrome).
• Hematologic Abnormalities: Anemia of chronic disease, thrombocytosis, or leukopenia.
• Skin Changes: Palmar erythema, vasculitis, and skin ulcers in severe cases.
Psychological Impact:
• Depression, anxiety, and emotional distress due to chronic pain and disability.
Diagnostic Evaluation
oMedical History and Physical Examination
• Detailed assessment of joint pain, stiffness, and swelling.
• Evaluation of family history of autoimmune diseases.
• Inspection for joint deformities and extra-articular symptoms.
Laboratory Investigations
• Rheumatoid Factor (RF):
• Positive in ~70-80% of RA patients.
• Indicates autoimmune activity but may be present in other diseases.
• Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies:
• Highly specific for RA, especially in early stages.
• Erythrocyte Sedimentation Rate (ESR):
• Elevated, indicating inflammation.
• C-Reactive Protein (CRP):
• Increased in active inflammation.
• Complete Blood Count (CBC):
• Anemia of chronic disease.
• Thrombocytosis in active disease.
• Antinuclear Antibody (ANA) Test:
• May be positive, though less specific for RA.
Imaging Studies
• X-ray:
• Early stages show soft tissue swelling and joint space narrowing.
• Advanced stages reveal joint erosion and deformities.
• Ultrasound:
• Detects synovial inflammation and joint effusions.
• Magnetic Resonance Imaging (MRI):
• Identifies early bone erosion and soft tissue involvement.