Rheumatoid arthritis 2

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Rawalpindi Medical college

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Rheumatoid arthritis 2

  1. 1. Rheumatoid Arthritis Prof. Dr. M.Shoaib Shafi FCPS (Pak) FCPS (Bangladesh) FACP (USA) FRCP (London) FRCP (Edin) FRCP (Ire) FRCP (Glasgow) Professor of Medicine, Rawalpindi Medical College Councillor and Vice President, College of Physicians and Surgeons Pakistan
  2. 2. • Is a lifelong progressive disease that produces significant morbidity, and premature mortality in some • 50% have to stop work after 10yrs
  3. 3. Epidemiology • May present at any age • Commonly, late child bearing age in females, and 6th-8th decade in males • Female: Male 3:1 difference diminishes in old age. • Affects 1% of population
  4. 4. Pathology • Symmetrical deforming polyarthropathy, affecting the synovial membrane of peripheral joints • Has a genetic component, but many do not have a FHx
  5. 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. 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. 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 disease if have RhA Uncommon: • vasculitis • Pyoderma gangrenosum • Pericardial effusions • Pulmonary effusions • Diffuse interstitial fibrosis • Scleritis • Mononeuritis multiplex • C1-2 -> myelopathy
  8. 8. Bloods • Anaemia of chronic disease • ESR + CRP ^ - acute phase reactants ▫ CRP is more specific than ESR ▫ Not always ^ in small joint disease • RhF - +ve in 50% • Include U+E’s, LFT’s pre-DMARD use
  9. 9. • Anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) assay.
  10. 10. Radiology • • • • Xray hands (include wrists) and feet Loss of joint space Soft tissue swelling Erosions – particularly look 5th MC & MT & ulnar styloid, & scaphoid/trapezium • Peri-articular osteoporosis • Joint destruction
  11. 11. 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
  12. 12. Diagnosis • Distribution of joint involvement • Morning stiffness • Active synovitis. Inflammation (swelling, warmth, or both) on examination • Symptoms for > 6 weeks • RhF, ESR, CRP
  13. 13. 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
  14. 14. Who to refer • >12w • 3 or more joints • Skin rash - ? vascultis
  15. 15. Treatment • To relieve pain & inflammation • Prevent joint destruction • Preserve / improve function
  16. 16. 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
  17. 17. MDT • • • • • • • GP Rheumatologist Specialist rheumatology nurses + help line Physio + hydrotherapy OT Pharmacist Phlebotomist
  18. 18. NSAID’s • Symptom relief • Minimal role in altering disease process
  19. 19. 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
  20. 20. 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
  21. 21. 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
  22. 22. 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
  23. 23. 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
  24. 24. 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
  25. 25. 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.
  26. 26. 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
  27. 27. 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 nonimmune 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
  28. 28. 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
  29. 29. Penicillamine Rarely used!
  30. 30. 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
  31. 31. • 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    
  32. 32. 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
  33. 33. 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)
  34. 34. 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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