Rheumatoid arthritis 2

Rheumatoid ArthritisProf. Dr. M.Shoaib ShafiFCPS (Pak) FCPS (Bangladesh) FACP (USA)FRCP (London) FRCP (Edin) FRCP (Ire) FRCP (Glasgow)Professor of Medicine, Rawalpindi Medical CollegeCouncillor and Vice President, College of Physicians and Surgeons Pakistan

•Is a lifelong progressive disease that produces significant morbidity, and premature mortality in some

•50% have to stop work after 10yrs

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

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 disease if have RhA

Uncommon:• 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 disease

•RhF - +ve in 50%

•Include U+E’s, LFT’s pre-DMARD use

•Anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) assay.

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

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)