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Rheumatoid Arthritis

Rheumatoid Arthritis. 8 th September 2005 South Worcestershire VTS Dr A Walder. Is a lifelong progressive disease that produces significant morbidity, and premature mortality in some 50% have to stop work after 10y. Epidemiology. May present at any age

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Rheumatoid Arthritis

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  1. Rheumatoid Arthritis 8th September 2005 South Worcestershire VTS Dr A Walder

  2. Is a lifelong progressive disease that produces significant morbidity, and premature mortality in some • 50% have to stop work after 10y

  3. Epidemiology • May present at any age • Commonly, late child bearing age in females, and 6th-8th decade in males • Affects 1% of population

  4. Pathology • Symmetrical deforming polyarthropathy, affecting the synovial membrane of peripheral joints • Has a genetic component, but many do not have a FHx

  5. Presentation • May have a fulminant onset, but commonly insidious over weeks to months • Classically small joints initially – PIP’s, MCP’s, MTP’s • Pain, swelling, stiffness – esp early morning • Can affect any synovial joint - may involve TMJ, cricoarytenoids, or SCJ’s • Spares DIP’s (cf OA & psoriatic arthritis) • May involve C1-2 articulation – rarely affects the rest of the spine

  6. O/E • Early -> boggy warm joints in typical distribution • Hands – ulnar devation, swan neck & boutoniere’s deformity, tendon rupture • Wrists – radial devation, volar subluxation, synovial proliferation may compress median nerve • Feet – sublux at MTP’s, skin ulceration, painful ambulation • Large joints – affects whole joint surface in symmetrical fashion eg med & lat compartment of knees • Synovial cysts eg Baker’s cyst of the knee, ganglions

  7. Extra –articular manifestations Common: • Fatigue, wt loss, low grade fever • Subcutaneous nodules; • almost exclusively sero-positive pt’s • thought to be triggered by small vessel vasculitis • Carpel & tarsal tunnel syndromes • Capsulitis eg shoulder • Increased mortality & morbidity from CVS dx if have RhA Uncommon: • ‘Polyartritis nodosa-like’ vasculitis • Pyoderma gangrenosum • Pericardial effusions • Pulmonary effusions • Diffuse interstitial fibrosis • Scleritis • Mononeuritis multiplex • C1-2 -> myelopathy

  8. Bloods • Anaemia of chronic disease • ESR^ + CRP ^ - acute phase reactants • CRP is more specific than ESR • Not always ^ in small joint dx • RhF - +ve in 50% • Include U+E’s, LFT’s pre-DMARD use

  9. Radiology • Xray hands (include wrists) and feet • Loss of joint space • Soft tissue swelling • Erosions – partic look 5th MC & MT & ulnar styloid, & scaphoid/trapezium • Peri-articular osteoporosis • Joint destruction

  10. Differential Diagnosis • Viral syndromes – hep B or C, EBV, parvovirus, rubella • Psoriatic arthritis • Reactive arthritis • Enteropathic arthritis • Tophaceous gout • Ca pyrophoshate disease (pseudogout) • PMR • OA • SLE • Hypothroid association • Sarcoidosis • Lyme disease • Rheumatic fever

  11. Diagnosis • Distribution of joint involvement • Morning stiffness • Active synovitis. Inflammation (swelling, warmth, or both) on examination • Symptoms for > 6 weeks • RhF, ESR, CRP

  12. Diagnosis (American College of Rheumatology) • Morning stiffness* • Arthritis of 3 joint areas* • Arthritis of hands* • Symmetric arthritis* • Sero +ve • Radiological changes • * for greater than 6 weeks

  13. Who to refer • >12w • 3 or more joints • Skin rash - ? vascultis

  14. Treatment • To relieve pain & inflammation • Prevent joint destruction • Preserve / improve function

  15. Treatment • Early diagnosis is essential • Aim to treat with DMARD’s at 3 months • Once RA damage is done radiologically, it is largely irreversible. This usually occurs within first 2 years of the disease • The goal is to put the disease into remission

  16. MDT • GP • Rheumatologist • Specialist rheumatology nurses + help line • Physio + hydrotherapy • OT • Pharmacist • Phlebotomist

  17. NSAID’s • Symptom relief • Minimal role in altering disease process

  18. Gluccocorticoids • Symptom relief • Some slowing of radiological progression • Prednisolone > 10mg/d is rarely indicated • Avoid using without a DMARD • Use to bridge effective DMARD therapy • Minimise duration and dose • Always consider osteoporosis prophylaxis

  19. Methotrexate • Oral 7.5mg - ^ by 2.5mg every 6w to max 25mg. ONCE WEEKLY (allows liver to recover) • Is an anti-metabolite, cytotoxic drug, which inhibs DNA synthesis & cellular replication • Lower dose in elderly & renal impairment as its renally excreted • Folic acid (3d after methotrexate) thought to decrease toxicity • Avoid cotrimoxazole, trimethoprim, XS ETOH, live vaccines • Give annual flu jab • Can be given subcut if oral absorption poor

  20. Methotrexate cont….. • SE’s: oral ulcers, nausea, hepatotoxicity, bone marrow suppression, pneumonitis • All respond to dose reduction except pneumonitis • Stop 3/12 before pregnancy – remember males • Pre-Rx: FBC, U+E, LFT, CXR, Pt education • Monitoring: • every 2/52 for 1st 2/12. • then every 1/12

  21. Methotrexate • Withhold and d/w rheumatologist if; • WBC < 4 • Neuts <2 • Plts< 150 • > x2 ^ AST, ALT • Unexplained low albumin • Rash or oral ulcers • New or ^ing dyspnoea • Ix if MCV > 105 (B12/ Folate) • Deterioration in renal func – decease dose • Abnormal bruising or sore throat – stop and check FBC

  22. Sulfasalazine / Salazopyrine • 500mg/day - ^ by 500mg weekly to 2-3g/d • Pre-Rx: FBC, LFT, U+E • Monitor: • FBC, LFT every 2/52 for 8/52 • then 1/12 for 10/12 • Then every 3/12 after 1y’s treatment • Stop and d/w rheumatologist as indicated before • Headaches, dizziness, nausea – decrease dose

  23. Hydroxychloroquine • Least toxic • Is an anti-malarial • Yearly optician review – retinal toxicity • 200-400mg/d • Often used in combo with other DMARD’s • Check U+E prior to starting • Avoid in eye related maculopathy, diabetes or other significant eye disease • Consider stopping after 5 years • Yearly bloods

  24. Leflunomide (Arava) • 100mg for 3 days, then 20mg/d, can decrease to 10mg/d • 2nd line treatment. Is a new drug. • Should not be used with other DMARD’s • May inhibit metab of warfarin, phenytoin, tolbutamide • Long elimination half life – so may react with other DMARD’s even after stopping it • Must not procreate within 2y of stopping. Do serum levels.

  25. Leflunomide cont….. • SE’s: blood dyscrasias, hepatotoxicity, mouth ulcers, skin rash (inc stevens-johnson & toxic epidermal necrolysis), mild ^BP, GI upset, wt loss, headaches, dizziness, tenosynovitis, hair loss. • If severe SE’s – elim with cholestyramine 8g or activated charcoal • Pre-Rx: FBC, U+E, LFT, BP • Monitor: FBC, LFT, U+E, BP • Every 2/52 for 6/12 • Then every 8/52 • Withhold as above

  26. Azathioprine • 1mg/kg/d - ^ after 4-6/52 to 2-3mg/kg/d • Immunosuppressant, antiproliferative, inhibits DNA synthesis • Lower dose in hepatic or renal impairment • If on allopurinol cut dose by 25% • Avoid live vaccines • Give pneumovax and flu jab • Passive immunisation for varicella zoster in non-immune pts if exposed to chicken pox or shingles • Pre-Rx: FBC, U+E, LFT • Monitor: • Every 2/52 for 2/12 & after every dose change • Then every 1/12

  27. Gold / Sodium Aurothiomalate (Myocrisin) • 10mg im test dose (done in clinic) then 20mg, then weekly 50mg to dose of 1g – then reassess • Pre-Rx: FBC, U+E, LFT, urinalysis • Monitor: • FBC and urinalysis at each injection • Results to be available at next dose • Each time ask about oral ulcers & rashes • Withhold as above

  28. Penicillamine Rarely used!

  29. Cyclosporin • Is an immunosuppressant • 2.5mg/kg/d in 2 divided doses. ^ after 4/52 by 25mg to max 4mg/kg/d • Avoid in renal impairment or uncontrolled BP • Numerous drug interactions -> BNF • Need to ½ dose of diclofenac • Avoid colchine & nifedipine • Use k-sparing diuretics with care • Avoid grapefruit juice & live vaccines

  30. Pre-Rx: FBC, U+E X2, LFT, lipids, BP X2, 24 hour creatinine clearance • Monitor: FBC, LFT, ESR, BP • 2/52 till on stable dose for 3/12 • Then 1/12 • LFT’s every 1/12 until on stable dose for 3/12 then every 3/12 • Serum lipids every 6/12 – 1 year • Withhold and d/w rheumatologist; • ^ by 30% of baseline creat • Anormal bruising • ^K • ^BP^lipids • Plts < 150 • >X2 ^ of AST, ALT, ALP

  31. Anti-TNF alpha • Use for highly active RhA in adults who have failed at least 2 DMARD’s, including methotrexate • Etanercept 25mg subcut twice a week • Infliximab 3-10mg/kg iv every 4-8 weeks • Adalimumab 40mg subcut alternate weeks • Rapid onset (days to weeks) • Disadvantages: cost & unknown long term effects, infections, demyelinating syndromes • Should be given with methotrexate • High risk atypical infections – low threshold for abx prophylaxis

  32. IL-1 receptor antagonist • Not commonly used yet! • Anakinra 100mg/d subcut • In combo with methotrexate • Slower onset than anti-TNF • SE; injection site reactions, pneumonia (esp in elderly with asthma)

  33. Conclusion • RhA is a lifelong dx • Ideally want an early diagnosis • MDT + pt education • Effective new drugs • Safe monitoring (pt + MDT responsibility)

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