1. Management of Rheumatoid arthritis, Osteoarthritis & Gout Dr. Eoin Casey MD FRCPI, FRCP

2. Background Reading Davidson’s Principles & Practice of Medicine, 50 th Anniversary Ed, 2002 Davidson’s Principles & Practice of Medicine, 50 th Anniversary Ed, 2002 Musculoskeletal disorders, Ch 20: pg 957-1047 Musculoskeletal disorders, Ch 20: pg 957-1047 Clinical Assessment of the Musculoskeletal System (handbook) Arthritis and Rheumatism Council UK Clinical Assessment of the Musculoskeletal System (handbook) Arthritis and Rheumatism Council UK http://www.arc.org.uk/about_arth/opubs/6321/6321.pdf

3. General Assessment History History Clinical examination Clinical examination Functional anatomy Functional anatomy Physiology Physiology Investigations Investigations Major manifestations of musculoskeletal disease Major manifestations of musculoskeletal disease

4. Symptoms & Signs Joint pain Joint pain Stiffness Stiffness Swelling Swelling Inflammation Inflammation Skin changes Skin changes Muscle changes Muscle changes Deformity Deformity Non-specific systemic symptoms Non-specific systemic symptoms (weight ↓ ; appetite ↓ ; energy ↓ ; concentration ↓ ; mood ↓ ) (weight ↓ ; appetite ↓ ; energy ↓ ; concentration ↓ ; mood ↓ )

5. Osteoarthritis Aetiology is unknown

6. Aims of management Educate the patient Educate the patient Control pain Control pain Optimise function Optimise function Beneficially modify the disease process Beneficially modify the disease process

7. “It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has.” William Osler 1849-1919 William Osler 1849-1919

8. Management of OA Patient’s personality Patient’s personality Attitude Attitude Holistic factors Holistic factors - activities of daily living - activities of daily living - co-morbid disease - co-morbid disease Availability, cost & logistics of evidence-based intervention Availability, cost & logistics of evidence-based intervention

9. Patient education Randomized controlled trials have shown that education results in substantial improvement and prolonged benefit Randomized controlled trials have shown that education results in substantial improvement and prolonged benefit

10. Management of OA Exercise Exercise - aerobic fitness - aerobic fitness - local strengthening exercises - local strengthening exercises Weight reduction Weight reduction Simple analgesia Simple analgesia - eg Paracetamol 1g 4-6 hrly - eg Paracetamol 1g 4-6 hrly Non-steroidal anti-inflammatory drugs Non-steroidal anti-inflammatory drugs - (NSAIDS) - (NSAIDS)

11. NSAIDS >40 NSAIDS available in Ireland >40 NSAIDS available in Ireland Top most prescribed drugs in the world Top most prescribed drugs in the world In favour of their use are In favour of their use are - effectiveness - effectiveness - lack of toxicity - lack of toxicity - affordability - affordability Variable individual tolerance and response Variable individual tolerance and response Non-responders to one agent may improve with another Non-responders to one agent may improve with another

12. NSAIDS Mechanism of Action Mechanism of Action - ↓ prostaglandin levels - ↓ prostaglandin levels - inhibit cyclooxygenase (COX) - inhibit cyclooxygenase (COX)

13. Cyclo-oxygenase isoforms COX I COX I - housekeeping enzyme - housekeeping enzyme - expressed in gastric mucosa, platelets & kidney - expressed in gastric mucosa, platelets & kidney COX II COX II - inflammatory enzyme - inflammatory enzyme - expressed in various tissues largely at sites of inflammation - expressed in various tissues largely at sites of inflammation

14. The COX II controversy

15. Selective COX II inhibitors

16. Gastric side effects of NSAIDS GIT toxicity - up to 30% GIT toxicity - up to 30% Aetiological factor in 30% gastric ulcers Aetiological factor in 30% gastric ulcers 10% of RA/OA patients hospitalised annually for NSAID associated bleeding 10% of RA/OA patients hospitalised annually for NSAID associated bleeding Endoscopic evidence of ulceration in 20% of NSAID users even in absence of symptoms Endoscopic evidence of ulceration in 20% of NSAID users even in absence of symptoms 2000 deaths per annum in UK 2000 deaths per annum in UK

17. Risk factors for NSAID gastritis Age > 60 years Age > 60 years Past history of PUD Past history of PUD Past history of adverse effects with NSAIDS Past history of adverse effects with NSAIDS Steroid use Steroid use High doses High doses Multiple NSAIDS Multiple NSAIDS Specific NSAIDS eg Indomethacin, Azapropazone Specific NSAIDS eg Indomethacin, Azapropazone ↓ risk - Proton pump inhibitors; Ranitidine ↓ risk - Proton pump inhibitors; Ranitidine Cyto-protection with Mesoprostil Cyto-protection with Mesoprostil

18. NSAIDS side effects Older people are at greatest risk for Older people are at greatest risk for - renal - renal - cardiovascular - cardiovascular - GIT toxicity - GIT toxicity

19. Other treatment modalities Nutri-pharmaceuticals Nutri-pharmaceuticals - Glucosamine - Glucosamine - Chondroitin Sulphate - Chondroitin Sulphate Topical agents Topical agents Physiotherapy Physiotherapy Occupational therapy Occupational therapy

20. Rheumatoid arthritis Aetiology is unknown

21. Approach to management Holistic approach to assessment Holistic approach to assessment Education is as important as medications Education is as important as medications NSAIDS NSAIDS Corticosteroids Corticosteroids Disease modifying agents (slow acting) Disease modifying agents (slow acting)

22. Steroids in Rheumatoid Arthritis Glucocorticoids in low doses <7.5mg daily are very effective to bridge the gap of the latent period before disease modifying drugs work Glucocorticoids in low doses <7.5mg daily are very effective to bridge the gap of the latent period before disease modifying drugs work Local intra-articular steroid injections Local intra-articular steroid injections

23. Disease modifying agents Hydroxychloroquine Hydroxychloroquine Salazopyrine Salazopyrine Penicillamine Penicillamine Gold Gold Methotrexate Methotrexate Azathioprine Azathioprine Luflunomide Luflunomide Cyclophosphamide, Cyclosporine Cyclophosphamide, Cyclosporine Anti TNF agents Anti TNF agents eg Adalimumab (Humira), Etanercept (Embrel), Infliximab eg Adalimumab (Humira), Etanercept (Embrel), Infliximab

24. Non-drug treatments Physiotherapy Physiotherapy Physical treatments Physical treatments Surgery Surgery Coping strategies Coping strategies

25. Gout

26. Gout Crystal deposition Crystal deposition Negatively bi-refringent sodium monouric crystals in joints, bursa, tendons and kidney Negatively bi-refringent sodium monouric crystals in joints, bursa, tendons and kidney Not always associated with hyperuricaemia Not always associated with hyperuricaemia

27. Stages of Gout 1. Acute Gout 1. Acute Gout 2. Inter critical periods 2. Inter critical periods 3. Chronic tophaceous Gout 3. Chronic tophaceous Gout

28. Treatment of acute attack One of the most painful conditions known One of the most painful conditions known NSAIDS NSAIDS Colchicine (main s/e diarrhoea) Colchicine (main s/e diarrhoea) Steroids Steroids

29. Long term management Uricosuric agents Uricosuric agents - Allopurinol 100mg od increasing to 300mg od - Allopurinol 100mg od increasing to 300mg od - MOA: Xanthine oxidase inhibitor - MOA: Xanthine oxidase inhibitor - 2-3 weeks after acute attack - 2-3 weeks after acute attack - initiation may precipitate an acute attack - initiation may precipitate an acute attack

30. Gout in Older People Association with thiazide diuretics Association with thiazide diuretics Increased toxicity to Allopurinol Increased toxicity to Allopurinol