8. rheumatoid arthritis lau chak-sing

Rheumatoid Arthritis
Western Medicine Perspectives
September 2013
CS Lau
Daniel CK Yu and Chair Professor
Division of Rheumatology & Clinical Immunology
The University of Hong Kong

Outline of presentation
• Clinical presentation of RA
– Articular, extra-articular and radiological features

• The immunology of RA
• Diagnosis of RA
– Classification criteria to aid diagnosis
– The importance of early diagnosis

• Management of RA – an overview of drug
treatment

RA - epidemiology

• Commonest cause of autoimmune
inflammatory polyarthritis
• Found in all races with variable
prevalence
• 1 - 2% in Caucasians
• 0.3 - 0.4% in Chinese
• Rare in the blacks

• Peak age of onset: 35 - 55 years
• Female : Male = 3 : 1

RA – a erosive synovial disease

RA – a erosive synovial disease

Arthroscopic appearance of a
normal joint

Normal
synovium

© ACR

Arthroscopic appearance of a
rheumatoid joint

Rheumatoid
synovium

© ACR

Histological appearances of normal and
rheumatoid synovium

Proliferating synovial
fibroblasts

New blood
vessels

Other cell populations

Infiltrating
lymphocyes
Normal
synovium

Rheumatoid
synovium

Rheumatoid
synovium

Normal
synovium

Dendritic cells
B lymphocytes
Plasma cells
Mast cells
Osteoclasts
CD68+
macrophage

CD3+ T cells

Mab 67+
Type B
synoviocytes
IL-1

© ACR

© ACR

TNF

DR

DC = Dendritic cell
IL = Interleukin
Mø = Macrophage
RF = Rheumatoid factor
TCR = T cell receptor
TNF = Tumour necrosis factor

TCR
CD4
CD4

DC

Stimulatory
Inhibitory

Activated T-cell CD4

Antigen
presentation

Unknown antigen

B

TNF

Plasma
cell

Mø
TNF
IL-6

TNF, IL-6, IL1

Ig, RF
Anti-CCP

Chondrocytes

Synoviocytes

Osteoclasts

Endothelial cells

Cartilage degradation
Joint space narrowing

Synovial hyperplasia
Joint inflammation

Bone resorption
Bony erosion

Neovascularisation
Recruitment of
inflammatory cells

RA – Early X-ray changes
Soft tissue swelling

RA – Early X-ray changes
Peri-articular osteopenia

RA – Late X-ray changes
Peri-articular erosive lesions

RA – Advanced X-ray changes
Bony destruction with deformities

The progressive course of RA
Early RA

Intermediate

Inflammation

Late

Destruction

Severity (arbitrary units)

Disability

0

5

10

15

20

25

30

Duration of Disease (years)
Adapted from Kirwan. J Rheumatol. 1999;26:720-725.

RA – A chronic, serious, prevalent disease

 serious comorbidities such
as heart disease, infection,
and malignancies2
 a 5–10 year reduction in
life expectancy3
 reduced quality of life
compared with other
serious conditions4
 a considerable economic
burden4

Mean value

 A global prevalence of around 24 million cases1
 RA is associated with
90
80
70
60
50
40
30
20
10
0

Healthy controls
Patients with RA

1. World Health Organization. The global burden of disease: 2004 update. (www.who.int/healthinfo/global_burden_disease/2004_report_update);
2. Boonen A, Severens JL. Clin Rheumatol 2011;30(Suppl 1):S3-S8; 3. Kvien TK. Pharmacoeconomics 2004;22(2 Suppl 1):1-12; 4. Lundkvist J, et al. Eur J Health
Econ 2008;8(Suppl 2):S49-S60. Figure reproduced from Science Photo Library, London, UK.

15

Classification criteria for RA
Score
• 1 large joint
• 2-10 large joints
• 1-3 small joints (with/without large joint
involvement)
• 4-10 small joints (with/without large joint
involvement)
• >10 joints (at least 1 small joint)

0
1
2

Serology

• RF and anti-CCP negative
• Low +ve RF or low +ve anti-CCP
• High +ve RF or high +ve anti-CCP

0
2
3

Acute phase reactants

• Normal CRP and normal ESR
• Abnormal CRP or abnormal ESR

0
1

Duration

• <6 weeks
• ≥6 weeks

0
1

Joint involvement

≥6/10 = Rheumatoid arthritis

3
5

The need to diagnosis RA early
Clinically
uninvolved

Clinically
involved

Control
CD68+ macrophage

CD3+ T cells

Mab 67+ type B
synoviocytes

IL-1

TNF
Kraan et al A&R 1998; 1481-8

The need to treat RA early
Early Disease

Early
Disease
Reversible functional disability
Irreversible functional disability

The need to treat RA early
Early Disease

Advanced Disease

Early
Disease

Advanced
Disease

Reversible functional disability
Irreversible functional disability

Conventional drug treatment for RA
• Symptomatic treatment
– Non-steroidal antiinflammatory drugs
– Simple analgesics

• Local corticosteroids

• Disease modifying antirheumatic drugs
–
–
–
–
–
–
–
–

Azthioprine
Cyclosporine
Hydroxychloroquine
IM gold injection
Leflunomide
Methotrexate
Penicillamine
Sulphasalazine

DR

DC = Dendritic cell
IL = Interleukin
Mø = Macrophage
RF = Rheumatoid factor
TCR = T cell receptor
TNF = Tumour necrosis factor

TCR
CD4
CD4

DC

Biologic therapies
for RA

Stimulatory
Inhibitory

Activated T-cell CD4

Antigen
presentation

Unknown antigen

B

TNF

Plasma
cell

Mø
TNF
IL-6

TNF, IL-6, IL1

Ig, RF
Anti-CCP

Chondrocytes

Synoviocytes

Osteoclasts

Endothelial cells

Cartilage degradation
Joint space narrowing

Synovial hyperplasia
Joint inflammation

Bone resorption
Bony erosion

Neovascularisation
Recruitment of
inflammatory cells

Monitoring
RA

Alternative therapies for RA

• Patients want to try alternative therapies
– 335/402 patients – alt therapies in the past 1 year
– 243/335 are current users
– Mean cost per year = HK$10447 (~US$1400)
• Dietary supplements
• Vitamins
• Fish oil
• Evening primrose oil
• Green lipped mussels
• Minerals
• Copper bracelet
• Magnet necklace
• Bee sting

•
•
•
•
•
•
•
•

Scorpions
Bone setting
Traditional Chinese Medicine
Lingzhi / yunzhi
Tu-na
Qi gong
Taichi
Spa / balneotherapy
Combe et al 2007

Monitoring
RA

Summary

• RA is a common chronic autoimmune disease of the
joint
• Poorly treated, there is significant morbidity and
mortality
• The goal of treatment is to achieve remission
• Early patient identification and treatment is essential
• Multiple treatment regimens are available
• Clinicians should work together to control the
disease

Combe et al 2007

8. rheumatoid arthritis lau chak-sing

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