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Rheumatoid Arthritis

A Review
Samir Albreshni Acknowledgements: Dr R Gorodkin

Objectives
Definitions of arthritis and rheumatoid arthritis Review the epidemiology of RA Disease course and complications Basic investigations

Briefly review of disease management

What is arthritis?
An inflammatory condition that affects the joints
Inflammation:
Excessive heat Swelling Pain Redness Loss of function

What is rheumatoid arthritis?


One of over 100 types of arthritis
Symmetrical Chronic No known underlying cause

Characterised by changes in the synovial membranes Results in deformity and immobility.

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)

Risk Factors

Age and gender Genetic Hormonal and reproductive Infections Socioeconomic Lifestyle

Genetic
Genetic factors may predispose some individuals to
RA (concordance in twin studies; familial clustering)

The presence of HLA-DR4 antigen may confer up to


a 7x increased risk

The DRB1 gene is believed to be a predictor of


severe and persistent disease

PTPN22 and PAD14

1987 ACR Classification Criteria


1. Morning stiffness lasting at least one hour 2. Arthritis (swelling) of 3 or more joint areas 3. Arthritis (swelling) of hand joints 4. Symmetric arthritis 5. Positive rheumatoid factor 6. Subcutaneous nodules 7. Erosions on x-rays of hands and wrists To qualify as RA, need 4 of 7 for at least 6 weeks

New ACR and EULAR criteria


>=6 points: joint involvement, serology, duration of synovitis, acute phase reactants

Signs and symptoms


Joint swelling Morning stiffness Symmetry

Ulnar deviation Subluxation Boutonniere and swan-neck deformities Z-deformities of the thumb

How does RA start?


70% - insidious onset of joint pain, stiffness, and swelling over months
20% - subacute - over weeks 10% - acute onset Occasionally episodic progressing to persistent disease 50-90% of patients have progressive disease; few will experience remission

What joints are commonly affected?


Temporomandibular 20-30%
Cervical spine 40-50% Shoulder 50-60% Elbow 40-50% Wrist 80-90%

MCP 90-95% PIP 65-90%


Hip 40-50%
Knee 60-80% Ankle 50-80% MTP 50-90%

What is actually going on in the joint?

Established Rheumatoid Arthritis

Normal knee

Damaged Knee

Summary of XR changes
RA
Excess soft tissue Juxta-articular
osteopaenia Loss of jt. space Bony erosions Subluxation

OA

Loss of jt. space Subchondral sclerosis Subchondral cysts Marginal osteophytes

Laboratory Tests
FBC

Anaemia Thrombocytosis Acute phase response ESR / CRP / Alk P Raised immunoglobulins Rheumatoid factor Anti-CCP antibody

Rheumatoid Factor
Not unique to rheumatoid arthritis Present in about 80% of patients with RA Does not cause rheumatoid arthritis Associated with more severe disease NOT A BLOOD TEST FOR ARTHRITIS!!!!

Is rheumatoid arthritis limited to the joints?

NO!!!

Extra-articular Manifestations

Anaemia Sicca syndrome Pericarditis Pleuritis/ Pulmonary Fibrosis Subcutaneous Nodules Ocular Inflammation Neuropathies Vaculitis Splenomegaly (5% - only 1% is Feltys synd.) Amyloidosis

Nodule

Normal Lungs

Severe Pulmonary Fibrosis

Results:
Pain
Disability Loss of work

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


3

SMR

1 0.8
UK UK
Sweden USA/ Canada Finland

Mortality - Cardiac
3

SMR

1 0.8
UK UK
Sweden USA/ Canada Finland

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

Malignancy
SIR
5
Finland, 1978 Sweden, 1993 Denmark, 1996 Scotland, 2000

3 2

0.5

All cancers

NHL

Lung cancer

Colorectal cancer

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

Economic Impact
In the US, the total cost of RA is estimated at more
than $32 billion (20 billion).

Direct 8 billion (hospitalization, medicines,


surgery) Indirect 12 billion (loss of income, loss of work days, disability assistance)

Employer medical and work-loss claims twice as high


in patients who have RA

So how can we treat it??

Treatments
Analgesics Steroids DMARDS (disease modifying anti-inflammatory

drugs) Physiotherapy OT Podiatry Surgery

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)

History of Anti-Rheumatic Therapy


Cortisone Antimalarials Sulfasalazine Azathioprine Cyclophosphamide Etanercept Leflunomide Infliximab

Aspirin Willow Bark

Gold

Penicillamine

Methotrexate

Antiquity 1899 1935

1950

1960

1970

1987

1998

1999

DMARDS
Antimalarials eye involvement Methotrexate monthly blood tests Sulphasalazine 3 monthly blood tests
Steroids osteoporosis, early DM, early
cataracts, weight gain, skin thinning

What is a Biologic Drug?


Derived from living organisms

3 biologics commonly used for RA:


Etanercept Adalimumab Infliximab

All block the action of TNF


Key cytokine which drives inflammation and
damage in RA Recently CD20 depleting agent (Rituximab)

IL6 receptor inhibitors (Tucilizumab)

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.

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

New drugs emerging with increased efficacy but long term


risks unknown

Thank you
Any Questions

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