1. Giant cell arteritis and Polymyalgia rheumatica
Dr. S. Bhalara
Rheumatology unit
West Herts Trust

2. Madonna and Cannon van der Paele – Jan Van Eyck (1436)
This is one of the most renowned of the flemish painters of the 15th centuary. Because of his early mastery of the technique, he is thought to be the father of oil painting. This is entitled the Madonna and Cannon Van der Paele. Who is the artist?
Someone in the painting has a rheumatological disease - headache jaw claudication and early visual loss.

3. Madonna and Cannon van der Paele – Jan Van Eyck (1436)
Temporal arteritis
Visual symptoms- 1mg/kg till symptoms abate – (1month)
No visual symptoms 40mg predn and reduce
Often need steroid sparing drugs mtx/aza/mmf

4. Ostial stenosis L common carotid
L subclavian occluded
Ostial stenosis L common carotid
It must be remembered that this is the commonest of the vasculitides and Although tA often affected a more apt term is GCA recogizing that other cranial and extra cranial vessels may be affected. This is an MR angiogram of a patient that presented with a systemic inflammatory syndrome characterised by upper limb claudication and tia’s

5. PET scan fdg showing in another pt showing hi uptake in aortic and subclavian vessels

6. Syndrome Clinical features Overall frequency Cranial arteritis
headaches
+++
Scalp tenderness ++
Jaw claudication – painful chewing/talking
Ocular symptoms – partial/complete visual loss, amaurosis fugax, ocular motor deficit +
Tongue claudication
CNS ischaemia – VB insufficiency, confusion, cortical blindness
dysphagia
Large vessel arteritis
Limb claudication
Absent peripheral pulses
Asymmetrical BP readings
Systemic inflammatory syndrome with arteritis
Fever, malaise, fatigue,
anorexia, weight loss,
depression
Synovitis of peripheral joints (wrists)

7. Acute ischemic optic neuropathy in GCA – disc is swollen with indistinct margins later atrophy with pallor

9. GCA: incidence Iceland Sweden Norway Denmark Asian – Takayasu’s
Highest
Lowest
Iceland
Sweden
Norway
Denmark
Asian – Takayasu’s
African
Scandinavian ancestry is an important risk factor

10. Investigations: acute phase
ESR, CRP, IL normal in 25% of biopsy proven cases
Weyand et al Arthritis Rheum 2000;43:1041
Normochromic, normocytic anaemia
Reactive thrombocytosis
Normal esr should not exclude GCA or the need for biopsy
Not known whether any specific marker is has a higher spec or sens for TA

11. Temporal artery biopsy
All patients with suspected TA (not pmr only)
Biopsy should not delay steroid therapy

12. Temporal artery biopsy
Yield
Retrospective cohorts – % positivity rate
Hall et al Lancet 1983;2:1217
Skip lesions – long length of biopsy needed
Increase in yield of 7-13% by biopsying other side - Eular guidance biopsy both sides
Mukhtyar et al Ann Rheum Dis 2009;68(3):318
Mayo clinic achieves a pos bx rate
Eular guidance biopsy both sides – frozen section of 1st side and if neg do other side.

13. Temporal artery biopsy
Timing
535 consecutive TA Bx
Positive biopsies
Steroid naive – 31%
Steroid treated – 35%
Positive biopsies at least 14 days post steroids
Achkar et al Ann Int Med 1994;20(12):987
Mouse models – vascular inflammation difficult to eradicate histologically even with high dose steroids
Black et al J Clin Invest 1997;99:2842
We don’t know how long steroid therapy takes to get rid of biopsy findings but mouse models suggest that histological change of vasc inflammation is actually not that easy to eradicate with steroids

14. Negative / no TA biopsy 535 consecutive TA Bx
95% chance of negative biopsy if
ESR<40
No jaw claudication
No TA tenderness
Synovitis
Gabriel et al 1995;22(1):93
Steroid trial – failure of response to high dose steroids > 1 week – GCA unlikely
No other plausible alternative- treat
? Shorter more rapid reduction regime

15. GCA: treatment Oral corticosteroids immediately
If visual loss in 1 eye -risk of blindness in second eye = 70% in 1 week
Once steroids started risk of visual loss is low
Visual disturbance – mg/kg prednisolone (60-80mg/day)
Single morning dose as effective as split dose
Alternate day dosing ineffective
No visual symptoms – 40mg
Pulse IV methylpredn may reduce long term steroid requirements Mazlumzadeh et al Arthritis Rheum 2006;54:3310
Pulse iv methyl pred 15mg/kg ie 1000mg on 3 consequtive days may allow more rapid steroid taper

16. GCA: Corticosteroid taper
Response may be considered as diagnostic criterion
Once reversible symptoms resolve and acute phase improves -50% (approx 1 month)
10% every 2 weeks to 20mg at 3-4 mths and 10mg at 6mths
Below 10mg – reduce by 1mg/month
Most pts respond rapidly and response considered diagnostic
Occlusive symptoms eg visual symptoms, jaw or limb claudication may not resolve

17. Relapse during corticosteroid taper
Only need modest increases in steroid doses
Refractory disease
Azathioprine
Methotrexate Jover et al Ann Int Med 2001;134:
Hoffman et al Arthritis Rheum 2002;46:1309
Mycophenolate mofetil, ciclosporin, leflunomide, tacrolimus, anti-TNF
Most relapses only need increases in steroids to last effective dose
Most immunosuppresants used as steroid sparing have been tried in GCA evidence is scant – can be very useful in some pts and in others nothing works either for pmr or gca
2 studies for mtx one found possible benefits jover and the other none hoffman
Infliximab ineffective in 1 study

18. Adjuvant therapy Low dose Aspirin Osteoporosis prophylaxis
Retrospective study – reduces visual loss and CVA rate Nesher et al Arthritis Rheum 2004;50:1332
Osteoporosis prophylaxis
GI protection – PPIs
Antifungals – (amphotericin lozenges etc)

19. Polymyalgia rheumatica
50% of GCA pts develop PMR
25% already have myalgias at time of diagnosis of GCA
15% of PMR patients develop GCA
Brooks Arch Int Med 1997;27:157(2):162
Complicated as myalgia and lethargy is a major feature of steroid withdrawal

20. Polymyalgia rheumatica
Cause?
Vasculitic
Subclinical vasculitis of temporal arteries seen
Vascular production of inflammatory mediators – IL-1, TGF-B, IL-2 (even without cellular infiltrate)
Circulating activated macropages/monocytes
Capsulitic
Imaging/histology shows synovitis/bursitis in shoulders
Often associated synovitis, tenosynovitis and oedema in hands and feet
Not a muscle disease (despite the name)

21. Polymyalgia rheumatica
Often very acute onset
Bilateral (symmetrical)
Pains may be widespread but proximal limb girdle predilection
Chest wall symptoms
Morning stiffness /systemic symptoms
Systemic symptoms- malaise lethargy
shoulder girdle alone can predominate and I’ve seen cases with chest wall symptoms

22. Investigations: acute phase
ESR, CRP, IL-6
Normochromic, normocytic anaemia
Reactive thrombocytosis
Liver enzymes (esp alk phos)

23. Investigations: acute phase
ESR < 40mm/hr in 7-22%
Helfgott Arthritis Rheum 1996;39(2):304
Gonzalez Arch Int Med 1997; 157(3):317
Gabriel J Rheumatol 1999;26(6):1333
? CRP more reliable
Steroid trial (10-20mg for 1-2 weeks)
Some diagnostic criteria include steroid response

24. Link with arthritis Synovitis – seronegative arthritis often seen
Late onset rheumatoid arthritis – PMR very common presenting feature Gonzalez J Rheumatol 2000;27:2179
Inflammatory oedema – RS3PE
Seroneg arthritis often seen –hands wrists often responds to the steroids and is of good prognosis

25. Differential diagnosis
Malignancy
Paraneoplastic musculoskeletal syndrome
Metastatic disease
Myeloma
Fibromyalgia
Vitamin D deficiency
Hypothyroidism
Cervical and lumbar spondylosis/spinal stenosis
Bursitis/tendonitis

26. PMR therapy Steroids Steroid sparing drugs 15-20mg prednisolone
maintain 2-4 weeks after resolution of symptoms
Taper by 10% every 2-4 weeks
Once below 10mg/day by approx 1mg/month
Benign diagnosis – adjust according to symptoms – ESR/CRP guides but does not dictate therapy
Steroid sparing drugs
20% steroid resistant (must exclude paraneoplastic syndrome or CTD/RA)
Methotrexate Caporali Ann Int Med 2004;141:568
azathioprine/mycophenolate/leflunomide
NSAID therapy alone is acceptable
1 double blind rct of low dose mtx 10mg/wk reduces steroid requirements greater no pts off steroids fewer flares

27. PMR prognosis No increase in mortality
Survival in 315 PMR patients longer than controls Myklebust et al Scand J Rheumatol 2003;32::38
Use steroids/immunosuppresants with caution
Recurrence rate approx 20%
PMR causes increased bone turnover in it’s own right – Osteoporosis prophylaxis
Scandinavian cohort – longer than expected survival -

28. Discussion: How should we manage GCA in West Herts?
Suspected GCA Primary care start high dose steroids visual symptoms Secondary care AAU urgent OPD Review Opthalmology acute medicine Rheumatology Neurology COE TA Biopsy Opthalmology Gen surgeons Vascular surgeons Follow up and Opthalmology Rheumatology COE General Med Neurology steroid taper GP