1. POLYMYALGIA & GIANT CELL ARTERITIS
RHEUMATOLOGY MATTERS!
POLYMYALGIA & GIANT CELL ARTERITIS

2. Polymyalgia Rheumatica and Temporal Arteritis

3. Polymyalgia and Temporal Arteritis.
Clinical syndromes which represent different ends of a disease spectrum.
Affects elderly patients--is rare below 50.
Respond to steroids.

4. Classification of Symptoms.
Systemic--malaise, anorexia, fever, night sweats, weight loss, depression.
Myalgic--proximal, symmetrical muscle pain and stiffness in PMR.

5. Classification of arteritic symptoms
Pain, swelling, erythema over affected artery.
Partial occlusion resulting in claudication-like symptoms.
Total occlusion resulting in ischaemia and necrosis (can occur anywhere in body).

6. Polymyalgia Rheumatica
Stiffness in morning which may worsen again in the evening.
May literally have to roll out of bed in morning.
Muscle strength generally preserved.

7. Temporal Arteritis. Almost only seen in Caucasians.
Pain commonly around temporal artery, jaw and post auricular artery.
Less common presentations may lead to pain in tongue, throat and teeth.
Loss of pulsation of artery is a debatable sign.
Histology reveals giant cell arteritis in 80% of cases.

8. Ophthalmic Features.
Sudden, painless deterioration of vision in one eye, usually on waking.
Visual acuity varies from 6/6 to no light perception.
Fundus examination reveals optic disc oedema with splinter retinal haemorrhages.
Starts as unilateral condition but may progress to bilateral disease.

9. Other Manifestations of GCA.
Giant cell artertitis can affect all arteries.
One study revealed 8 out of 244 patients with new stroke had GCA or PMR.
May lead to isolated cranial nerve palsies.
GCA can affect coronary arteries which may lead to myocardial infarct.
Great vessels can be affected, there is an association with aortic incompetence.

10. Diagnosis PMR in particular is a diagnosis of exclusion.
History is critical. Systemic, local and visual symptoms should be sought.
Examination should include full cardiovascular and neurological review as well as eliciting local arteritic signs.
The examination in PMR tends to be normal.

11. Differential Diagnosis for PMR.
Neoplastic disease.
Cervical spondylosis.
Rheumatoid arthritis.
Connective tissue disease.
Myeloma and leukaemia.
Bone disease (osteomyelitis).
Hypothyroidism.
Miliary TB.

12. Differential Diagnosis of TA.
Dental conditions.
Trigeminal neuralgia.
Otological conditions.
Retinal vascular accident.
Other causes of opthalmoplegia.

13. Investigations
ESR/Plasma viscosity raised in 80% but very non-specific.
ALP marginally raised in 30-50%.
Other features include thrombocytosis, raised IgG and a normocytic, normochromic anaemia.
Histology remains the gold standard.

14. Histology. Biopsy of artery only justified if arteritis suspected.
A negative biopsy dose not exclude TA.
Giant cell arteritis is characterized by skip lesions.
An inch of artery should be removed, preferably from a tender area.

15. J.W. male d.o.b.3/10/34 Oct 91doing building work at home
myalgia thighs & buttocks
morning stiffness to mid afternoon
difficulty walking
lethargy

16. J.W. male d.o.b.3/10/34 Dec 91 progressively worse
shoulder girdle myalgia
unable to crouch/elevate arms
night sweats
no energy
no headaches

17. J.W. male d.o.b.3/10/34 normal temporal arteries no muscle tenderness
moderate restriction shoulders & hips
ESR 88
prednisolone 15 mgs/day
better in 48 hrs
ESR 14 within 2 weeks

18. J.W. male d.o.b.3/10/34 Dec 92: well on prednisolone 5 mg/day
Jan 93: altered bowel habit rectal bleeding rectal carcinoma resected
Nov 93: right knee effusion (ESR 7)
Aug 95: right shoulder synovitis prednisolone 1mg/day
July 96: stopped steroids. Well. ESR 9.

19. Mrs. D.E. female d.o.b.7/7/27
Oct 96: pain stiffness right hand shoulder,both knees
morning stiffness shoulder & pelvic girdles
anorexia & weight loss 9kg

20. Mrs. D.E. female d.o.b.7/7/27 Feb 96: severe headaches,flashing lights
pain in tongue & throat when eating
tender scalp & nodules on temples
anorexia & weight loss 15kg
O/E nodules (R) temporal artery no temporal pulse palpable
ESR90 , gamma GT 136
TA biopsy: active giant cell arteritis

21. Mrs. D.E. female d.o.b.7/7/27
prednisolone 40mg/day. resolutionof symptoms in days
1996/7: unable to keep disease suppressed with less than 15mg prednisolone/day
methotrexate added
steady reduction of steroid thereafter
July 99: well. Stopped steroid. Continues methotrexate. ESR19.

22. Polymyalgia Rheumatica and Giant Cell Arteritis
Steroid treatment
How much ?
How long ?
Complications

23. Polymyalgia Rheumatica
Initial dose: 15mg Prednisolone daily for 1 month
Reducing dose: by 2.5mg every 2-4 weeks to a dose
of 7.5mg - 10mg daily
then by 1mg every 4-6 weeks
Maintenance dose: 10mg by 6 months
5mg by 1 year
Most patients require steroid treatment for at least 3-4 years

24. Giant Cell Arteritis
Do not wait for the temporal artery biopsy - treat immediately.
Initial dose: 40mg Prednisolone daily for 8 weeks
80mg Prednisolone if eye symptoms
Reducing dose: by 10mg/day at weekly intervals to 40mg
and then 5mg/day to a dose of 10mg daily
from 10mg rduce at 1mg intervals as PMR

25. Common concerns with treatment
Do not reduce steroids too quickly.
Apart from acute relapsing eye disease do not increase steroid dose for about 1 week after an apparent flare. The flare may be short lived.
There is no place for Deflazacort.
Intra-muscular steriods are currently under investigation.
Early bone loss and diabetes should be considered
Beyond 1 year, steroid-sparing agents should be used if the steroid dose remains mg +.

26. Do phenotypes like age, sex, ESR, IL-6 help?
Maximum benefit - VS - Minimum side-effects
Can we stratify patients ?
Rapid responders
Remitting / Relapsing
Slow responders
Do phenotypes like age, sex, ESR, IL-6 help?
No!
Weyand et al. Mayo clinic. Arch. Int. Med. 3/1999

27. Steroid induced Osteoporosis
Common
Early onset (2.5% loss 3 months. 5% loss 1 year)*
Mechanisms:
decreased calcium absorption
increased urinary calcium excretion
decreased sex hormones
reduced osteoblast formation
decreased muscle mass
effects on growth factors
Prevention of bone loss with cyclical etidronate**
* Lo Casio et al. Bone & Mineral Research.Aug’ 90
** Adachi et al. New Eng. J. Med. 1997;337

28. Steroid induced Osteoporosis
Accounts for 10% of osteoporosis in both sexes.
Walsh et al BMJ Aug. 1996:
Nottinghamshire study: GP population of 65,786.
303 cases (65% female) on ‘continuous’ steroids
mean daily dose 8mg
mean duration of 3 years
23% RA 22% PMR 19% CAL

29. Results:
Only 14% of people taking any preventative treatment for osteoporosis in the last 4 years.
Only 10% of women over the age 45 and on steroids were taking HRT.
Assuming the study representative of general population then approx 250,000 people in the UK, on steroids, were not on prophylaxis.
Hospital based practice? - Worse!!!
Reid et al. Aberdeen study (BMJ 1998)

30. Mrs T 74yrs Jan 1993 - 3yr history of temporal headaches
- Inconclusive TA biopsy (1992)
- Treated successfully with steroids (3 days)
Recurrence of temp.headaches, also aches in shoulder girdles, Rt. buttock & thigh
O/E - Tender TA. ESR=70
On Prednisolone 30mg for 3 days

31. Temporal Artery Biopsy Results
“Sections of temporal artery show focal duplication and loss of elastic lamina but with no associated inflammation. Features represent a healed stage of temporal arteritis.”
NB: steroid therapy for 7 days

32. ESR vs Prednisolone

33. Osteoporosis Assessment
Menopause yrs
# R wrist yrs
# L patella yrs
Steroid therapy
c/o spinal pain - Thoracic wedge #
DXA scan - results

34. Osteoporosis Treatment
1993
Rocaltrol 250 nanograms b.d
Sandocal 1g o.d
Calcitonin 50units 3 times weekly for 4 months
1996
Lowering BMD - Alendronate 10 mg o.d
1998
Improved BMD

35. Serial lumbar spine bone density

36. Subsequent course of condition
Symptoms responded & did not recur but ESR 40-90mm/h
1994 Pred.5mg ESR40
1995 Pred.4mg ESR51
1997 Pred.3/2mg ESR46
1998 Pred.2/1mg ESR46
1999 Pred.1mg ESR27

37. Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties
The Normal ESR

38. What is the ESR? Rate of agglutination of red cells
determined by fibrinogen level
fibrinogen is an Acute Phase Reactant
main stimulus Interleukin-6
source of IL-6 in PMR/GCA?
IL-6 level correlates with disease activity

39. Is PMR/GCA a viable diagnosis with a normal ESR?
Retrospective analysis of cohorts of PMR cases:
1) Gonzalez et al : ESR<40 20% of 201 cases
more frequent in:
men; younger patients
less fever
no weight loss
no anaemia or electrophoretic abnormalities

40. 2) Helfgott & Kieval : ESR<30 20% of 117 cases
men more frequent
higher Hb
much longer disease duration before treatment

41. Are these cases really PMR/GCA?
Retrospective studies
cases already included on clinical grounds
in ACR GCA criteria ESR excluded from classification tree due to low specificity
best predictor is temporal artery tenderness or decreased pulsation

42. Summary PMR/GCA can be present in the absence of an elevated ESR
generally indicates less severe disease

43. Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties
The Young Patient

44. often associated with malignancy no trials
very rare under 50 years
often associated with malignancy
poor steroid response
no trials

45. The Normal Temporal Artery
Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties
The Normal Temporal Artery

46. variable percentage of biopsies in GCA are positive
?poor selection
previous steroid therapy
‘some’ PMR patients have positive biopsies
? positivity rate in clinically normal arteries

47. SUMMARY do not overtreat PMR ‘in case’ of GCA
consider prevention of steroid-induced osteoporosis
atypical cases of GCA/PMR occur rarely