1. 1031 MD4

3. Jane is a 45 year old woman, who presents to her doctor complaining of morning stiffness of the joints of her fingers for several weeks now with pain. There is also a swelling of her knee joints. She says the pain Improves as she does her daily chores but Tylenol is ineffective in alleviating the pain. On inspection subcutaneous nodules are found behind the olecranon process with a cyst found on the popliteal fossa. What are the differentials for this patient?

4. Presents from early childhood(rare) to late old age. Most commonly 30-50 years. Worldwide distribution. 0.5-3% of the population Women before menopause are affected more than men (3:1)

5. HLA DR4 occurs in 50-75% of patients Presence of pentapeptide QK/RAA in 3 rd allelic hypervariable region of HLA-DRB1 increases susceptibility Positive rheumatoid factor and anti-citrullinated protein antigen(more specific for RA) When rheumatoid factor is present with HLA DR4, susceptibility increases 13 times. This rheumatoid factor is typically of IgM type, and is an auto-antibody to the Fc portion of IgG.

6. Inflammation of the synovial lining of joints, tendon sheats & bursae-synovitis Synovium becomes greatly thickened, with proliferation & infilteration by inflammatory cells(lymphocytes and macrophages) Hyperplastic synovium(pannus) spreads to cartilage surface & damages the underlying cartilage by blocking its normal routes of nutrition & by effects of cytokines on the chondrocytes. Fibroblasts from the proliferating synovium also grow along the course of blood vessels between the synovial margins and epiphyseal bone cavity and damage the bone.

8. Pain and stiffness of the small joints of the hands(MCP,PIP) and feet(MTP) Wrist, elbow, shoulders, knees and ankles are also affected Carpal tunnel syndrome Pain & stiffness worse in the morning, improves with activity

10. Morning stiffness>1 hour Arthritis of three or more joints 6 weeks or more Arthritis of hand joints and wrists Symmetrical arthritis Subcutaneous nodules Positive serum rheumatoid factor Typical radiological changes(e.g. Erosions, loss of joint space) Four or more criteria necessary for diagnosis

11. Blood count-ESR & CRP are raised Serology-Rheumatoid factor present in 70% of cases, anti-citrullinated protein antigen(more specifc, 85% of cases) Aspiration of the joint-the aspirate looks cloudy owing to white cells X-ray-Boutonniere deformity, ulnar deviation of fingers

12. Rose weeler test(most specific): ability of IGM rheumatoid factor to agglutinate sheep red cells that have been coated with rabbit anti-sheep antibody. Latex agglutination test: rheumatoid factor agglutinates latex particles that have been coated with human IgG

13. No curative agent for Rheumatoid Arthritis Use NSAIDS & analgesics to control symptoms If synovitis recurs, refer to a rheumatologist to start DMARDs like Methotrexate, sulfasalazine(cytokine inhibition) Other drugs-Gold(sodium aurothiomalate), corticosteroids, anti-malarials If no improvement, consider anti TNF-α(infliximab) Physiotherapy has been found to be very helpful in slowing progression

14. Septic Arthritis-Staphylococcus Aureus Amyloidosis Caplan syndrome(coal miners lung+rheumatoid factor) Interstitial pneumonitis + fibrosing alveolitis Anemia of chronic disorders

15. Sarah is a 64 year old lady. She was diagnosed with Rheumatoid Arthritis 6 years ago. Her Rheumatoid arthritis was initially treated with methotrexate and sulfalazine which brought the disease under control. Recently Sarah has had several flares and this has resulted in several spells of corticosteroid therapy(among other treatment). Sarah later suffers a prolonged flare which doesn’t respond well to synthetic DMARD treatment. Her rheumatologist suggests commencing treatment with infliximab in addition to methotrexate. What risk associated with biological drug treatment should you be particularly aware?

16. Kumar and clark clinical medicine www.nhs.co.uk Robbins textbook of pathology www.umm.edu