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Rheumatoid Arthritis
8th September 2005
South Worcestershire VTS
Dr A Walder
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• Is a lifelong progressive disease that produces significant morbidity, and premature mortality in some
• 50% have to stop work after 10y
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Epidemiology
• May present at any age
• Commonly, late child bearing age in females, and 6th-8th decade in males
• Affects 1% of population
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Pathology
• Symmetrical deforming polyarthropathy, affecting the synovial membrane of peripheral joints
• Has a genetic component, but many do not have a FHx
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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
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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
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Extra –articular manifestationsCommon: • 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
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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
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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
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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
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Diagnosis
• Distribution of joint involvement
• Morning stiffness
• Active synovitis. Inflammation (swelling, warmth, or both) on examination
• Symptoms for > 6 weeks
• RhF, ESR, CRP
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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
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Who to refer
• >12w
• 3 or more joints
• Skin rash - ? vascultis
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Treatment
• To relieve pain & inflammation
• Prevent joint destruction
• Preserve / improve function
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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
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MDT
• GP
• Rheumatologist
• Specialist rheumatology nurses + help line
• Physio + hydrotherapy
• OT
• Pharmacist
• Phlebotomist
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NSAID’s
• Symptom relief
• Minimal role in altering disease process
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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
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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
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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
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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
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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
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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
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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.
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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
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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
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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
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Penicillamine
Rarely used!
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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
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• 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
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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
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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)
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Conclusion
• RhA is a lifelong dx
• Ideally want an early diagnosis
• MDT + pt education
• Effective new drugs
• Safe monitoring (pt + MDT responsibility)