RHEUMATOID
ARTHRITIS
PRESENTED BY HEENA
AMNA
Subgroup: 6th
Student of Medical faculty No.2
A chronic
progressive
disease causing
inflammation in
the joints and
resulting in
painful deformity
and immobility,
especially in the
fingers, wrists,
feet, and ankles.
EPIDEMIOLOGY
Prevalence: Rheumatoid arthritis (RA) is estimated to affect approximately
0.24 to 1 percent of the population.
Sex: ♀ > ♂ (3:1); predominantly affects middle-aged women.
Incidence: The annual incidence of RA in the United States and northern
European countries is estimated to be approximately 40 per 100,000 persons
Peak incidence: 50–75 years.
Prevalence of self-reported rheumatoid arthritis, by age and sex, 2017–18
ETIOLOGY
Chronic inflammatory
autoimmune disorder of
unknown etiology
Genetic disposition: RA appears
to be associated with specific
HLA types (HLA-DR4, HLA-DR1).
Hypotheses suggest the etiology
is multifactorial, with the
following factors playing a role:
Environmental triggers (e.g.,
infection, tobacco)
Hormonal factors
PATHOPHYSIOLOGY
• Initially, non-specific inflammation affects the synovial tissue, which is
later amplified by activation of T-cells (autoimmune response).
• With time, it may lead to inflammatory joint
effusion and synovial hypertrophy, as well as progressive destruction
and deterioration of cartilage and bone.
• Synovial lining hyperplasia
• Pannus formation along the synovial tissue → produce proteinases →
destroy cartilage extra-cellular matrix
• Patients with positive rheumatoid factor (RF) are more likely to
develop extra-articular manifestations of rheumatoid arthritis.
Synovial pannus formation and bone invasion: proliferative granulation
tissue with mononuclear inflammatory cells
Angiogenesis
Synovial lining hyperplasia with mononuclear cell infiltrate
Perivascular inflammatory infiltrates
Fibrin deposition on synovial surfaces
Characteristic histology of rheumatic nodules:
central fibrinoid necrosis with histiocytes and surrounding epithelioid cells
SCHEMATIC REPRESENTATION OF
THE PATHOPHYSIOLOGY OF RA
1) Initially, non-specific inflammation of the
synovial tissue, joint swelling, osteoporosis
of the surrounding bones over the course of
disease, as well as the erosion;
2)Progressive destruction and deterioration
of cartilage and bone;
3)Complete joint destruction with
malpositioning and loss of mobility in the
end stage of the disease.
CLINICAL FEATURES
ARTICULAR MANIFESTATIONS:
• Polyarthralgia
• Symmetrical pain and swelling of affected joints (also at rest).
• Frequently affected joints:
• Metacarpophalangeal joints (MCPJs)
• Proximal interphalangeal joints (PIPJs)
• Wrist joints
• Knee joints
• Joints of the axial skeleton are usually spared except for the cervical spine
• Morning stiffness > 30 min; often improves with activity.
• Joint deformities
• "Rheumatoid hand" is characteristic, and can include the following
deformities:
• Deepening of the interosseous spaces of the dorsum of hand
• Swan neck deformity: PIP hyperextension and DIP flexion
• Boutonniere deformity: PIP flexion and DIP hyperextension.
• Hitchhiker thumb deformity (Z deformity of the
thumb): hyperextension of the interphalangeal joint with
fixed flexion of the MCP joint
• Ulnar deviation of the fingers
• Hammer toe
• Atlanto-axial subluxation
Female patient with RA: Swelling especially of the PIP joints
Hands of a male patient: Swan neck deformity on the 4th and 5th fingers
of the left hand with hyperextension of PIP joint and flexion of the DIP
joint. Also there is pronounced swelling of the MCP joint.
Common deformities of the lesser toes
Rheumatoid nodules:Multiple erythematous subcutaneous nodules
are visible at the MCP, PIP and DIP joints
EXTRA-ARTICULAR
MANIFESTATIONS:
Constitutional symptoms: low-grade fever, myalgia, malaise,
night sweats
Skin: rheumatoid nodules (common); non-tender, firm,
subcutaneous swellings (2 mm–5 cm)
Lungs: fibrosis, nodules, pleuritis, and pleural effusions
Eye: Keratoconjunctivitis sicca, scleritis, and episcleritis
Endocrine and exocrine glands: secondary Sjogren syndrome
Hematological: anemia of chronic disease
EXTRA-ARTICULAR MANIFESTATIONS:
• Other musculoskeletal
• Tenosynovitis and bursitis
• Carpal tunnel syndrome (entrapment neuropathy)
• Typical nocturnal paresthesia of volar hand and fingers I–III
• Atrophy of thenar muscles → difficulty making a fist; inability to oppose the
thumb
• Tarsal tunnel syndrome
• Heart: Pericarditis and myocarditis; higher risk of myocardial
infarction, stroke, and CHF
• Vascular: Peripheral vasculitis manifesting as livedo reticularis, Raynaud
phenomenon, purpura, necrosing fingertips or peripheral neuropathy
RHEUMATOID ARTHRITIS FACTSHEET
SUBTYPES AND VARIANTS
• RA of the cervical spine
• RA normally spares the thoracic and lumbar spine. In some cases, it initially affects
the cervical spine, causing early-morning neck pain at rest.
• Complication: atlanto-axial subluxation
• Life-threatening complication!
• Symptoms
•
•
•
•
Pain and stiffness of the neck
Neurological deficits, e.g., cervical radiculopathy with peripheral paresthesias
Deformity, e.g., stiffness and scoliosis
In some cases, symptoms of high spinal cord compression
• Slowly progressive spastic quadriparesis
• Hyperreflexia or positive Babinski reflex
• Respiratory insufficiency
• Diagnosis
• Extension and flexion x-rays of the cervical spine
• MRI
• Treatment: surgery if instability or myelopathy are present
• Felty syndrome
• Definition: Felty syndrome is a severe subtype of seropositive RA.
• Clinical features
• Clinical triad consisting of arthritis, splenomegaly, and neutropenia (leads to ↑ risk of
recurrent bacterial infections)
• Other symptoms: skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever,
and chest pain (indicating pleuritis or pericarditis)
• Diagnosis
• Leukopenia with selective neutropenia
• ↑↑ RF
• ↑↑ ACPA
• Treatment
•
•
•
•
DMARD: methotrexate
Alternative: cyclophosphamide
Prompt and aggressive antibiotic treatment for suspected infections
Consider splenectomy to treat leukopenia and improve the disease course.
DIAGNOSTICS
• ACR criteria for RA (ACR/EULAR classification criteria (2010)
LABORATORY TESTS
NON-SPECIFIC
PARAMETERS
SPECIFIC
PARAMETERS
(SEROLOGY)
SYNOVIAL FLUID
ANALYSIS
• ↑ Inflammatory markers: CRP, ESR correlate with inflammatory activity.
• ↑ Ferritin as an acute phase protein.
• Possibly leukocytosis, thrombocytosis
• Anemia of chronic disease
• Anti-citrullinated peptide antibodies (e.g., anti-CCP) --> Sensitivity >90%
• Rheumatoid factor (RF) --> IIgM autoantibodies against the Fc region of IgG, Low specificity
• Antinuclear antibodies (ANA): elevated in 30% of cases
• Synovial fluid is collected by joint aspiration.
• Findings : (1) Cloudy yellow appearance, (2) Sterile specimen with leukocytosis (WBC: 5,000–50,000/μL),
(3) ↑ Neutrophils, granulocytes and ragocytes, (4) ↑ Proteins, ↓ viscosity; (5) Possibly rheumatoid factor
IMAGING
• Conventional x-ray
• Dorso-palmar x-ray of both hands
• Radiological findings
• Early: soft tissue swelling, demineralization (juxta-articular)
• Late: joint space narrowing, erosions of cartilage and bone, demineralization
(generalized)
Even if radiographic findings are normal, RA is still possible!
• MRI: (with or without contrast), especially if cervical spine involvement is
suspected or in early stages
• Ultrasound: joint effusion, formation of pannus
• Further diagnostic measures: contrast-enhanced ultrasound, scintigraphy
KNEE JOINT DESTRUCTION IN RA
Anteroposterior x-ray of the
right knee
Severe erosive changes with
joint space narrowing and
valgus deformity
RA: X-ray of both hands (PA view)
Generalized decrease of bone
radiodensity & narrowing of the joint
spaces of MCP, PIP and wrist joints.
TREATMENT
• General measures
• For acute episodes of inflammation: cryotherapy
• Physical and occupational therapy
• Physical activity
• Acute anti-inflammatory therapy
• Indication: acute attack
• Glucocorticoids: given until DMARD's onset of action or as long-term therapy for highly
active RA.
• Prevention of osteoporosis: optimization of sufficient calcium and vitamin D intake
• NSAIDs and COX-2 inhibitors: symptomatic relief without improving prognosis
• PPI's are recommended because combining glucocorticoids with NSAIDs substantially
increases the risk of GI ulcers.
• Long-term anti-inflammatory therapy with disease-modifying antirheumatic
drugs (DMARDs)
• Induce immunosuppresion, leading to potential remission of RA
• Reduce mortality and morbidity by up to 30%
• Slow onset of action (≥ 6 weeks), so symptomatic treatment
with glucocorticoids and NSAIDs is often required
• Non-biologic agents
• Drug of choice: methotrexate (MTX)
• First-line treatment for moderate to severe RA
• Benefits: highly effective, relatively well-tolerated, low cost, possibly life-prolonging
• To minimize side effects, folic acid is recommended 24–48 hours after taking MTX.
• Biologic therapy
• Indication: moderate or severe disease activity remaining after three months
of DMARD therapy
• Should be combined with non-biologic DMARDs
• Tumor necrotic factor (TNF) α inhibitors: e.g., adalimumab, infliximab
PROGNOSIS
• Factors associated with poor prognosis
•
•
•
•
•
Prolonged disease progression without initiation of treatment
Late onset (> 60 years of age)
Sex: ♀
Smoking
Social factors (e.g., low socioeconomic status, low level of education)
• Laboratory tests associated with worsened prognosis if abnormally
elevated
•
•
•
•
CRP
ESR
ACPA
RF titer
THANK YOU FOR
YOUR ATTENTION
ANY QUESTIONS ?
NO....?
GREAT. GOODBYE