Giant Cell Arteritis&Polymyalgia Rheumatica

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:10.1038/nrrheum.2012.97

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;89:284-292

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 24-48 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): 376-86; DOI: 10.3238/arztebl.2013.0376

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:10.1038/nrrheum.2012.97

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 92-100% • May be useful for assessing large vessels • Role in monitoring?

41. C+D= Biopsy proven Giant Cell arteritis Bley et al AJNR October 2007 28: 1722-1727

42. 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. Herpes zoster Migraine Basal skull lesions Infiltrative retro orbital lesions TIA Mimics/differentials • 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