RHEUMATOID

ARTHRITIS
Rheumatoid Arthritis • Arthritis = Inflammation of the JOINTS
• Rheumatoid arthritis = chronic, autoimmune disorder that affects the
joints
• A large and growing health problem
• There are about 100 forms of arthritis
• The prevalence of arthritis increases significantly with age
• Females are more likely than males to suffer from arthritis
• Obese and overweight people are diagnosed with arthritis more
frequently than underweight or normal-weight individuals
• Physically inactive people develop arthritis more often than
physically active people
 EPIDEMIOLOGY
• Persons with the HLA-DR4 haplotype have a significantly higher
incidence of RA
Epidemiology

• Persons with RA have a shortened lifespan with cardiovascular

disease as the most common cause of death
• Mortality: results from conditions such as septicemia, pneumonia,
lung abscess, or pyelonephritis
 Etiology
• The cause of rheumatoid arthritis remains unknown but genetic,
Pathogenesis

hormonal, psychosomatic, immunologic factors and infectious causes

are known to play a role in the pathogenesis of RA
• Immunologic factors are involved in the articular and extraarticular
manifestations of the disease
 • RA - a chronic, multisystemic and autoimmune disorder and a
progressive inflammatory disorder of the joints
• Range from a mild illness of brief duration to progressive destructive
polyarthritis associated with systemic vasculitis
Pathogenesis

• Pathogenesis of RA:
1. Initiation of synovitis by the primary causative factor
2. Subsequent immunologic events that perpetuate the initial
inflammatory reaction
3. Transition of an inflammatory reaction in the synovium to a
proliferative, destructive process.
Clinical Manifestations • RA often begins with prodromal symptoms such as fatigue, anorexia,
weakness and generalized aching and stiffness not localized to
articular structure. The patient may display a wide variety of extra-
articular manifestation.
• If the conditions listed persist for at least 6 weeks, the patient is
designated to have classic RA.
• Prognostic markers
• high number of swollen joints
• high serum levels or APRs
• presence of IgM rheumatoid factor
• radiographic and functional abnormalities
• presence of HLA-DR4
PHYSIOLOGY OF JOINTS • Synovial (joint) fluid
• A transparent viscous fluid
• Lubricates the joint space and transport nutrients to the
ANATOMY AND

articular cartilage
• Arthrocentesis
• Constitutes a liquid biopsy of the joint
• A fundamental part of the clinical database
• Rheumatoid Factor (RF)
• Can be seen in normal individuals or in unrelated joint diseases
• Synovial fluid analysis
Diagnostic Evaluation 1. Low serum iron
2. Elevated ESR
3. Elevations in the alpha-2 and gamma globulin fractions
(polyclonal)
4. Mild to moderate decrease in serum albumin

• Felty's syndrome - RA with splenomegaly and leukopenia common

among in those aged 50-70 years old, females and of Caucasian
decent
 1. Soluble circulating immune complexes
•Causes vasculitis and parenchymal lesions (extra-articular manifestations)
Manifestations
2. Cryoglobulins
Immunologic

3. Decreased CH50
4. Decreased C2 and C4
5. Presence of ANA - found in 14-28% of the patients
 1. Cyclic Citrullinated Peptide Antibody (anti-CCP)
OTHER MARKERS
•Highly specific indicator for RA
•Present in about 69-83% of patients with RA and have specificities
ranging from 93-95%
2. Autoantibody against mutated and citrullinated vimentin (MCV)
•Highly specific markers for RA
•Measured by lateral flow immunoassay (LFIA)
Rheumatoid Factor
• RF's are immunoglobulin of any isotype (IgM, IgG or IgA) directed
against the Fc region of human or animal IgG.
• IgM RF are present in 70% of people with RA but is NOT specific to
RA
• Being RF positive correlates with:
• Severity of the disease (in general)
• Nodules
• Other organ system involvement (e.g., vasculitis, Felty’s
syndrome, Sjögren’s syndrome
Rheumatoid Factor
TESTS FOR RHEUMATOID FACTORS
1. Rose-Waaler test
• Historical test for the detection of RF
• Principle: PASSIVE agglutination; uses sheep red cells coated with IgG
2. Latex agglutination
3. Immunoturbidimetric assays
4. ELISA
Rheumatoid Factor
Cyclic Citrullinated Peptide Antibodies
• RA occurs when, during inflammation, some proteins become altered
via a process known as citrullination
• CCP antibodies: highly specific indicator for RA
• Anti–CCP IgG antibodies: present in 69% to 83% of patients with RA
and have specificities ranging from 93% to 95%
• CCP Specificity (>95%)
• CCP sensitivity (80%)
 Immune Complexes
• Vasculitis is associated with complexes made up of IgG and 7S IgM
OTHER MARKERS
RFs
Complement Levels
• Serum complement levels are usually normal in patients with RA,
except in those with vasculitis
Antinuclear Antibodies
• Found in 14% to 28% of RA patients
• Disease manifestation is the same in ANA-positive and ANA-negative
patients.
JUVENILE IDIOPATHIC • Juvenile rheumatoid arthritis (JRA)
• A pediatric replica of the condition that affects adults
• Causes include factors such as infection, autoimmunity, and trauma
• Incidence rate: 0.1 to 1.1/1000 in the US
Signs and Symptoms
• Onset before age 16 years
• Presence of arthritis (i.e., joint swelling for 6 consecutive weeks or longer)
ARTHRITIS

Immunologic Manifestations
• Rheumatoid Factors
• Immune Complexes
• Antinuclear Antibodies
 Major goals:
1. Reduce pain and discomfort
2. Prevent deformities and loss of joint function
3. Help the patient maintain a productive and active life

Traditional Treatment
TREATMENT

• Nonsteroidal anti-inflammatory drugs

• Prostaglandins

Corticosteroids and Glucocorticoids Corticosteroids

• Have anti-inflammatory and immunoregulatory activity
 Non–Biologic Disease-Modifying Antirheumatic Drugs
• Methotrexate
• Tofacitinib
TREATMENT

Biologic Disease-Modifying Antirheumatic Drugs

• Biologics are genetically engineered proteins derived from human
genes
The end