Rawalpindi Medical college

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. • Is a lifelong progressive disease that
produces significant morbidity, and
premature mortality in some
• 50% have to stop work after 10yrs

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. Pathology
• Symmetrical deforming polyarthropathy,
affecting the synovial membrane of peripheral
joints
• Has a genetic component, but many do not have
a FHx

6. 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

7. 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

12. 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

13. 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

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

15. 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

21. 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

22. Diagnosis
• Distribution of joint involvement
• Morning stiffness
• Active synovitis. Inflammation (swelling,
warmth, or both) on examination
• Symptoms for > 6 weeks
• RhF, ESR, CRP

23. 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

24. Who to refer
• >12w
• 3 or more joints
• Skin rash - ? vascultis

25. Treatment
• To relieve pain & inflammation
• Prevent joint destruction
• Preserve / improve function

26. 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

27. MDT
•
•
•
•
•
•
•
GP
Rheumatologist
Specialist rheumatology nurses + help line
Physio + hydrotherapy
OT
Pharmacist
Phlebotomist

28. NSAID’s
• Symptom relief
• Minimal role in altering disease process

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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.

36. 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

37. 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

38. 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

39. Penicillamine
Rarely used!

40. 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

41. • 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





42. 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

43. 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)

44. Conclusion
•
•
•
•
•
RhA is a lifelong dx
Ideally want an early diagnosis
MDT + pt education
Effective new drugs
Safe monitoring (pt + MDT responsibility)