Transcript Rheumatoid Arthritis

Rheumatoid Arthritis
8th 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
• Commonly, late child bearing age in
females, and 6th-8th decade in males
• Affects 1% of population
Pathology
• Symmetrical deforming polyarthropathy,
affecting the synovial membrane of
peripheral joints
• Has a genetic component, but many do
not have a FHx
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
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
Extra –articular manifestations
Common:
• Fatigue, wt loss, low grade fever
• Subcutaneous nodules;
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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
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
Radiology
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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
Differential Diagnosis
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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
Diagnosis
• Distribution of joint involvement
• Morning stiffness
• Active synovitis. Inflammation (swelling,
warmth, or both) on examination
• Symptoms for > 6 weeks
• RhF, ESR, CRP
Diagnosis (American College of
Rheumatology)
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Morning stiffness*
Arthritis of 3 joint areas*
Arthritis of hands*
Symmetric arthritis*
Sero +ve
Radiological changes
* for greater than 6 weeks
Who to refer
• >12w
• 3 or more joints
• Skin rash - ? vascultis
Treatment
• To relieve pain & inflammation
• Prevent joint destruction
• Preserve / improve function
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
MDT
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GP
Rheumatologist
Specialist rheumatology nurses + help line
Physio + hydrotherapy
OT
Pharmacist
Phlebotomist
NSAID’s
• Symptom relief
• Minimal role in altering disease process
Gluccocorticoids
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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
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
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
Methotrexate
• Withhold and d/w rheumatologist if;
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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
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
Hydroxychloroquine
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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
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.
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
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
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
Penicillamine
Rarely used!
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
• 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;
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^ by 30% of baseline creat
Anormal bruising
^K
^BP
^lipids
• Plts < 150
• >X2 ^ of AST, ALT, ALP
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
IL-1 receptor antagonist
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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)
Conclusion
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RhA is a lifelong dx
Ideally want an early diagnosis
MDT + pt education
Effective new drugs
Safe monitoring (pt + MDT responsibility)