1. Giant Cell Arteritis&Polymyalgia Rheumatica
Olabambo Ogunbambi
Consultant Rheumatologist
Hull Royal Infirmary

2. Epidemiology
Pathogenesis
Clinical Features
Investigations
Imaging
Mimics
Treatment

3. Giant cell arteritis Primary systemic vasculitis medium/large vessels
involves aorta & main branches
First described by Hutchinson 1890
Histological features described by Horton et al 1932

4. Epidemiology Most common vasculitis Europe/N america
Incidence increases with age
Women affected 2-3 times more commonly
Incidence increases with latitude
17/million in North American populations of Scandinavian descent (over age 50)
<12/million in South European populations
Rare in blacks and Asians

5. Pathogenesis Still much uncertainty Factors implicated Age
Genetic factors
Infection(?)
seasonal variation incidence

6. Pathogenesis Genetic factors HLA Association with HLA DRB1*04
TNF microsatellite polymorphisms
Functional variant VEGF gene
Polymorphisms in genes for IL-13, NOS2, TLR-4

7. Pathogenesis Both innate and adaptive immune factors implicated
Possible viral/other trigger
stimulates monocyte activation
Activated monocytes infiltrate adventitia of large arteries and recruit further monocytes/lymphocytes
Macrophages migrate to media and produce cytokines and growth factors responsible for damage to elastic lamina and intimal hyperplasia

8. Figure 1 Pathogenetic mechanisms operating in GCA
Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritis
Nat. Rev. Rheumatol. doi: /nrrheum

9. Pathology Affects extracranial branches of carotid artery
All layers of arterial wall involved
Inflammatory lesions contain
activated T cells
dendritic cells
macrophages
giant cell cells

10. Pathology

12. Clinical features Classic features related to artery involvement
- extracranial branches of carotid artery
Headache
-Sudden, severe, predominantly temporal
-May affect occipital, parietal, frontal areas
-often severe enough to disturb sleep

13. Clinical features Jaw claudication Occurs in 40-50% patients
Highly specific
Needs to be distinguished from jaw pain , TMJ dysfunction and trismus
Occasionally patients have intermittent claudication affecting tongue, swallowing muscles

14. Temporal artery abnormalities
Decreased or absent pulses
Tenderness
Thickening
Nodules
Redness

16. Clinical features Scalp tenderness -occurs in 30-50%
Worse with brushing/combing hair
Occasional patients develop scalp necrosis

17. Scalp necrosis in giant cell arteritis.
Mackie S L , and Pease C T Postgrad Med J 2013;89:

18. Clinic features Constitutional symptoms
fever, night sweats, weakness, weight loss
Less commonly seen compared to pre-steroid era
Patients with constitutional symptoms and high infl markers may be less likely to develop ischemic manifestations

19. Ophthalmic complications
Frequency of occurrence
Opthalmology studies:
50% of patients
Rheumatology studies:
20-30% of patients

21. Ophthalmic complications
Anterior ischemic optic neuritis
Most common cause visual loss
Due to interruption of flow in posterior ciliary arteries
Presents as sudden painless visual loss
May present as mist in VF progressing to blindness in hrs
Unilat visual loss may initially be missed by patient
May progress to contralat eye in 1-10 days

22. Ophthalmic complications
Other causes of visual loss
Central retinal art occlusion
Ischaemic retrobulbar neuropathy
Occipital infarction

23. Ophthalmic complications
Amaurosis fugax
-2-30% patients
-Best clinical predictor of visual loss
Diplopia
-ischemia of oculomotor nerve
-occurs in 5-6% patient

24. Ness, T; Bley, T A; Schmidt, W A; Lamprecht, P
The Diagnosis and Treatment of Giant Cell Arteritis
Dtsch Arztebl Int 2013; 110(21): ; DOI: /arztebl

25. Clinical features Large vessel involvement Distal ischemia
Limb claudication
Vascular bruits
May present as PUO
Aortic involvement possibly more common than recognised
-risk of aortic rupture/dilatation

26. Clinical features Neurological manifestations CVA
Mononeuropathies/polyneuropathies(rare)

27. Clinical features Resp tract symptoms (often missed) Cough Sore throat
Hoarseness

28. Clinical features Audiovestibular dysfunction Facial pain
Facial swelling
Odontogenic pain
Glossitis
Carotidodynia

29. Investigations Elevated ESR/CRP/PV
Inflammatory markers usually abnormal
Usual to check both CRP and ESR (or PV)

30. Investigations High fibrinogen/haptoglobin Thrombocytosis
Anemia of chronic disease
Elevated alkaline phosphatase
Anticardiolipin antibodies

31. Temporal artery biopsy
Considered Gold Standard
Recommended length > 2 cm
False neg
-Sampling error
-missed areas of inflammation
-Skipped lesions
-Arteritis limited to great arteries
Biopsy should be done preferably before treatment
Or soon as possible after starting treatment if required

32. Temporal artery biopsy
What is a positive biopsy?
-Transmural changes only
-What about adventitial changes only?
-“Healed” arteritis?
possible confusion with age related changes
Bilateral biopsies?

33. Temporal artery biopsy

34. Temporal artery biopsy

35. Temporal artery biopsy

36. Imaging High resolution colour doppler US
Can visualise both lumen and vessel wall
Vessel wall features of presumed inflammation
Seen as hypoechogenic mural thickening
-”halo”
Dependent on equipment, operator
NB “halo” reported in normal patient, PAN

37. Imaging Other features stenoses, occlusions
Sensitivity 88%, Specificity 78%
Precise role still not clearly defined

38. Figure 3 Ultrasonographical findings for GCA
Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritis
Nat. Rev. Rheumatol. doi: /nrrheum

39. a & b = normal artery
c & d= temporal arteritis

40. MRI Can demonstrate mural inflammatory enhancement Role in diagnosis?
Temporal artery involvement
Small studies: Sens 89-94%, Specificity %
May be useful for assessing large vessels
Role in monitoring?

41. C+D= Biopsy proven Giant Cell arteritis
Bley et al AJNR October :

42. A 62-yr-old female patient with histologically validated GCA
A 62-yr-old female patient with histologically validated GCA. Transverse contrast-enhanced, fat-suppressed, T1-weighted SE image at initial presentation (A) and after 10 months of corticosteroid treatment (C).
Bley T A et al. Rheumatology 2008;47:65-67

43. PET-CT Useful modality for assessing extent of disease involvement
May demonstrate subclinical vasculitis of great vessels
May provide information about response to treatment
Can only evaluate large arteries
Clinical utility still unclear

44. Patient presenting with PUO

45. Mimics/differentials
Herpes zoster
Migraine
Basal skull lesions
Infiltrative retro orbital lesions
TIA
Cluster headache
Cervical spondylosis
Sinus disease
Temporomandibular joint pain
Ear problems
CTD
Other systemic vasculitides

46. Classification criteria
Age at onset>50yrs
New headache
Temporal artery abnormality
Elevated ESR >50 (Westergren method)
Abnormal artery biopsy
Three or more features yield
Sensitivity 93.5%
Specificity 91.2%
Limited applicability in daily practice

47. Predictors of neuro ophthalmic complications/positive TAB biopsy
History
Jaw claudication
Diplopia
Physical exam
TA beading
TA prominence
TA tenderness

48. Treatment Recommended starting regimens Uncomplicated GCA
-no visual symptoms
-no jaw claudication
Start Prednisolone 40-60mg

49. Treatment Complicated evolving visual loss or hx amaurosis fugax
IV methylpred 500mg-1g daily for three days
Then Prednisolone 60mg daily

50. Treatment Other issues Bone protection
Bisphosphonate/calcium/vitamin D supplementation
PPI
Aspirin 75mg daily

51. Tapering 40-60mg prednisolone (not <0.75 mg/kg) continued
for 4 weeks
(until resolution of symptoms and laboratory abnormalities)
Then dose is reduced by 10mg every 2 weeks to
20 mg
Then by 2.5mg every 2- 4 weeks to 10 mg
Then by 1mg every 1-2 months provided there is no relapse

52. Monitoring
Frequency: Suggested review at Weeks 0, 1, 3, 6 then months 3, 6, 9, 12 in the first year
Features:
Headaches
Jaw and tongue claudication
Visual symptoms.
Vascular claudication of limbs, bruits, pulses
Blood pressure
Proximal pain and morning stiffness.
Disability related to GCA.

53. Monitoring Full blood count, ESR/CRP, urea and electrolytes, glucose
Every two yrs-CXR(?)
Bone mineral density

54. Management of relapse
Headache: treat with the previous higher glucocorticosteroid dosage
Headache and jaw claudication: treat with 60mg prednisolone
Eye symptoms: treat with either 60mg prednisolone or IV methylprednisolone

55. Steroid sparing agents
Limited evidence
Consider if recurrent relapses or difficulty reducing steroid dose
Methotrexate
Tocilizumab
small case series/case reports of efficacy
Cyclophosphamide

56. Complications/prognosis
Generally runs self limited course
Overall survival similar to general population
Permanent partial/complete loss of vision in 15-20%
Inc risk CV events inc MI, CVA & PVD
Risk aortic dilatation/aneurysmal rupture

59. Polymyalgia rheumatica
Highest incidence in Northern Europeans & people of Scandinavian ancestry
2-3 times more common than GCA
Occurs in 50% patients with GCA
5-30 % of patients with PMR may develop GCA
Some pathogenetic similarity to GCA

60. Polymyalgia rheumatica
Presentation with pain and stiffness of neck. Shoulder girdle and pelvic girdle usually at least 4 weeks duration
May be abrupt in onset
Symptoms and signs of systemic inflammation
Malaise, weight loss, low grade fever, swats
Elevated CRP/ESR.
Up to 20% may have normal ESR

61. Clinical features Up to 50% distal MSK features
Mild distal synovitis, bursitis
Occasionally swelling/pitting edema of hands, wrists
Carpal tunnel syndrome
Subjective weakness
Constitutional symptoms

62. Investigations Elevated CRP &/or ESR(PV)
Nonspecific abnormalities in other tests
Anemia, elevated alkaline phosphatase
US & MRI can demonstrate bursitis and synovitis
PET CT may demonstrate subclinical vasculitis

64. Differentials Rheumatoid arthritis
Remitting Seronegative Symmetrical Synovitis with Pitting Edema
Multifocal MSK problems
Bone disease
Inflammatory myositis
Fibromyalgia
Hypothyroidism
Parkinson’s disease

65. PMR treatment Dramatically responsive to steroids
Most response to Prednisolone <20mg/day
Dose gradually tapered
Tapering an art not science!
Monitor for relapse, features of GCA ,side-effects of GC

66. Steroid sparing Mostly conflicting and inconclusive data
Options tried include
Methotrexate
Biologics (anti-TNF agents)
Azathioprine

67. Summary
GCA & PMR are closely related disorders affecting middle aged/older people
Unknown cause but genetic and enviromental factors influence pathogenesis
GCA primarily affects aorta and extracranial branches
In GCA biopsy is important in confirming diagnosis
GC are cornerstone of treatment
Significant associated morbidity
Some patients have chronic course and require GC for several yrs

68. Questions/comments?

69. Question Jaw claudication A. is pathognomonic of GCA
B. is defined by pain on chewing
C. signifies extensive involvement of branches of the external
carotid artery
D. is classified as an ischaemic feature of GCA
E. is never due to atherosclerosis alone
S. Mackie and C Pease. Postgrad Med J 2013;89:

70. Question In the diagnosis of GCA
A. The American College of Rheumatology criteria are
useful diagnostic criteria in clinical practice.
B. Ophthalmological evaluation is necessary in the presence
of visual manifestations
C. Pain on opening the mouth is one of the typical ischaemic
manifestations of GCA
D. Jaw claudication is never caused by atherosclerosis
E. Aortic imaging should be routinely performed
S. Mackie and C Pease. Postgrad Med J 2013;89:

71. Thank you