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Rheumatoid Arthritis. Dr. Kimme Hyrich Consultant Rheumatologist. Learning Objectives. Review the epidemiology and clinical presentation of RA Appreciate the nature of the disease course and complications Understand the basics of diagnosis

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rheumatoid arthritis

Rheumatoid Arthritis

Dr. Kimme Hyrich

Consultant Rheumatologist

learning objectives
Learning Objectives
  • Review the epidemiology and clinical presentation of RA
  • Appreciate the nature of the disease course and complications
  • Understand the basics of diagnosis
  • Review the basic pathophysiology behind joint manifestations
  • Briefly review current approach to treatment
pre talk quiz true or false
Pre-talk Quiz - True or False
  • Rheumatoid arthritis is very rare with only 1 in 10000 people affected
  • Smoking may cause rheumatoid arthritis
  • Diet is important
  • Only 50% of patients with RA will be positive for RF
  • RA is characterised by an erosive arthritis
  • Most patients will have an excellent response to NSAIDs
  • The underlying cause of RA in thought to be infection
  • RA rarely affects the eyes
  • The most common cause of death in RA is infection
  • Patients with RA do not experience premature death
epidemiology of ra
Epidemiology Of RA

Worldwide disease, affects all ethnic groups

Females > males 3:1

Age onset - peak 35-45 years

Can effect children and the elderly

Occurs in about 1% of adult population (UK/US)

what joints are commonly affected
MCP 90-95%

PIP 65-90%

Temporomandibular 20-30%

What joints are commonly affected?

Cervical spine 40-50%

Shoulder 50-60%

Elbow 40-50%

Wrist 80-90%

Hip 40-50%

Knee 60-80%

Ankle 50-80%

MTP 50-90%

genetic risk factors
Genetic Risk Factors
  • Background risk: 1%
  • Children have 3x increased risk if parent affected
  • Siblings have 2-4x risk if sibling affected
  • Concordence in twins
    • Monozygotic 15% vs Dizygotic 4%
  • Strongest gene: HLA-DRB1
gender
Gender
  • Females >> Males
  • Difference most apparent premenopausal
  • Pregnancy – no affect on incidence although first onset not uncommon in first 12 months postpartum
  • Studies of exogenous hormone therapy inconclusive
lifestyle risk factors
Lifestyle risk factors

Smoking

Obesity

Diet??

Alcohol

infection
Infection
  • Lots studied: EBV, parvovirus
  • No convincing evidence to support role of infection in aetiology of RA
extra articular manifestations
Extra-articular Manifestations
  • Sicca syndrome
  • Pericarditis
  • Pleuritis/ Pulmonary Fibrosis
  • Ocular Inflammation
  • Neuropathies
  • Vasculitis
1987 classification criteria
1987 Classification Criteria
  • Morning stiffness lasting at least one hour
  • Arthritis (swelling) of 3 or more joint areas
  • Arthritis (swelling) of hand joints
  • Symmetric arthritis
  • Subcutaneous nodules
  • Positive rheumatoid factor
  • Erosions on x-rays of hands and wrists

To qualify as RA, need 4 of 7 for at least 6 weeks

antibodies in rheumatoid arthritis
Antibodies in Rheumatoid Arthritis
  • Rheumatoid factor (RF)
  • Anti-citrullinated protein antibody (ACPA)
    • Anti-CCP
rheumatoid factor
Rheumatoid Factor
  • An autoantibody
  • Directed against Fc of other antibodies
  • Present in 50% of patients at presentation
  • Present in 60-80% of patients with chronic disease
  • Role in RA unknown but associated with more severe disease
rheumatoid factor1
Rheumatoid Factor
  • Not unique to RA
      • Other connective tissue diseases
      • Chronic infections e.g. TB, SBE
      • Chronic liver disease
      • Cryoglobulinaemia
      • Neoplasms
      • Old age
  • NOT A BLOOD TEST FOR RHEUMATOID ARTHRITIS
anti citrullinated protein antibody acpa
Anti-citrullinated protein antibody (ACPA)

Peptidyl arginine deaminase (PAD)

slide42
ACPA
  • Anti-Cyclic Citrullinated peptide (anti-CCP)
  • Association with HLA-DRB1 and smoking
  • Limited evidence for direct pathogenic role
  • Diagnostic and prognostic marker
    • Sensitivity – 50% early, 75% established
    • Specificity – 98%
    • High overlap with RF
other blood tests
Other Blood Tests
  • Anaemia of chronic disease
  • Thrombocytosis
  • Increased ESR
  • Increased CRP
  • Increased ALP
results
Results:

Pain

Disability

Loss of work

Mortality

mortality
Mortality
  • RA can reduce life expectancy by 10 to 15 years
  • Mortality may approach 50% over 5 years in cases of severe disability
  • Patients with extra-articular involvement are twice as likely to die as those with joint involvement only
  • Co-morbidity and drug toxicity account for the majority of deaths
mortality all cause
Mortality – All Cause

3

2

SMR

1

UK

UK

0.8

Sweden

Finland

USA/

Canada

cardiac disease and ra
Cardiac Disease and RA
  • Increased risk of myocardial infarction

Watson. J Rheum 2003

RR: 1.6 (95% CI 1.5-1.7)

Solomon. Circulation 2003

RR: 2.0 (95% CI 1.23,3.29) female

slide48

Malignancy

SIR

Finland, 1978

5

5

5

5

Sweden, 1993

Denmark, 1996

3

3

3

3

Scotland, 2000

2

2

2

2

1

1

1

1

0.5

0.5

0.5

0.5

All cancers

NHL

Lung cancer

Colorectal

cancer

psychosocial impact
Psychosocial Impact
  • Depression affects up to 40% of patients and may impact compliance and reporting of symptoms
  • The divorce rate among people with RA is 70% higher than the national US average
  • Up to 50% of patients report changes in social roles; 75% decrease leisure activities
goals of ra treatment
Goals of RA Treatment
  • No constitutional symptoms (fever, malaise)
  • Returning to a normal work schedule
  • Minimizing the impact on activities of daily living
  • Changing the course of disease progression (slowing or stopping the disease)
  • A multidisciplinary approach
history of anti rheumatic therapy

Sulfasalazine

Azathioprine

Cyclophosphamide

Biologics

Leflunomide

Cortisone

Antimalarials

Aspirin

Willow Bark

Methotrexate

Gold

Penicillamine

Antiquity 1899 1935 1950 1960 1970 1987 1998

History of Anti-Rheumatic Therapy
corticosteroids in ra
Corticosteroids in RA
  • Not a mainstay of therapy
  • Can be used early as a bridging therapy in early disease or as a temporary “fix”
  • Intra-articular use for specific joints
methotrexate
Methotrexate
  • “Gold standard” DMARD
  • Mechanism of action in RA not certain
    • Folate antagonist
    • Increase extracellular adenosine
  • Side effects
    • Minor: mouth ulcers, nausea, hair loss
    • Major: bone marrow suppression, liver damage, pneumonitis
sulfasalazine
Sulfasalazine
  • Unknown mode of action
  • Side effects
    • Minor: nausea, rash
    • Major: leukopaenia, liver damage, fibrosing alveolitis
other dmards and immunosuppressants
Other DMARDS and Immunosuppressants
  • Gold
  • Antimalarials
  • Penicillamine
  • Azathioprine
  • Ciclosporin
  • Cyclophosphamide
biologic therapies
Biologic Therapies
  • First introduced around 1999
  • Targeted therapies to specific proteins or cells involved in inflammation
  • Monoclonal antibodies or engineered protein receptors
example biologic drugs
Example Biologic Drugs
  • Anti-TNF drugs
      • Etanercept
      • Infliximab
      • Adalimumab
  • IL1-RA
      • Anakinra
  • Anti-CD20
      • Rituximab
  • Anti-Il6
      • Tocilizumab
biologic therapy for rheumatoid arthritis
Biologic Therapy for Rheumatoid Arthritis
  • Very effective in clinical trials
      • Suppress disease activity
      • Slow erosions
      • Improve quality of life
  • No increase in serious adverse events compared to placebo.
  • Long term safety remains largely unknown
  • BUT very expensive and NICE controlled!
summary
Summary
  • A chronic disease of unknown cause affecting the joints and other tissues
  • Results in pain, disability, early mortality
  • A clinical diagnosis I.e. a constellation of findings by physician and lab, not just a blood test
  • Traditional therapy poorly tolerated over the long term
  • New drugs emerging with increased efficacy but long term risks unknown
pre talk quiz true or false1
Pre-talk Quiz - True or False
  • Rheumatoid arthritis is very rare with only 1 in 10000 people affected
  • Smoking may cause rheumatoid arthritis
  • Diet is important
  • Only 50% of patients with RA will be positive for RF
  • RA is characterised by an erosive arthritis
  • Most patients will have an excellent response to NSAIDs
  • The underlying cause of RA in thought to be infection
  • RA rarely affects the eyes
  • The most common cause of death in RA is infection
  • Patients with RA do not experience premature death