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 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

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

• 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• 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)

• 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

• GP

• Rheumatologist

• Specialist rheumatology nurses + help line

• Physio + hydrotherapy

• OT

• Pharmacist

• Phlebotomist

NSAID’s

• Symptom relief

• Minimal role in altering disease process

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

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;– 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

• 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;• ^ 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

• 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

• RhA is a lifelong dx

• Ideally want an early diagnosis

• MDT + pt education

• Effective new drugs

• Safe monitoring (pt + MDT responsibility)