1. Giant Cell Arteritis Julie Story July 27, 2006

2. Overview Typical case presentation Differential diagnosis Confirming the diagnosis Associated symptoms & conditions Treatment Monitoring The frontier

3. Arthritis Foundation 2001, Givre 2006, Hunder 2006. Classic Case Presentation 55 yo female (70%) Headache (50-75%) Fever (50%) Jaw pain with chewing (50%) Fatigue (40%) Monocular vision loss (15%) Non-productive cough (10%) Bilateral vision loss (5%) Arm claudication (3-15%)

4. Differential Diagnosis Migraine Infection Tempo-Mandibular Joint disorder Ischemia –Carotid stenosis or dissection –Atherothrombosis or embolus Vasculitis –Giant cell arteritis –Takayasu’s arteritis –Wegener’s granulomatosis Orbital mass Papilledema Demyelination of optic nerve

5. American College of Rheumatology GCA Classification Criteria 3 of the following: –≥ 50 yo at disease onset –Localized new headache –Tenderness or decreased temporal artery pulse –ESR > 50 mm/hr –Arterial biopsy with necrotizing arteritis with mononuclear cell predominance or granulomatous process with multinucleated giant cells 94% sensitive, 91% specific

6. Confirming GCA Diagnosis History Physical exam Labs Temporal artery biopsy Ultrasound not consistently helpful Good response to prednisone

7. Physical Exam Tender, thickened temporal arteries Carotid bruits Limited ROM of neck, shoulders, and hips

8. Arthritis Foundation Primer on the Rheumatic Diseases. Edition 12. 2001, Hunder G. Clinical Manifestations and diagnosis of giant cell (temporal) arteritis. UpToDate. 2006. Labs ESR > 100 mm/hr Acute phase reactants – Increased CRP –Increased fibrinogen –Decreased albumin Anemia Microscopic hematuria Increased AST and alk phos Elevated factor VIII and Von Willebrand factor Elevated IL-6

9. Arthritis Foundation Primer on the Rheumatic Diseases. Edition 12. 2001, Hunder G. Clinical Manifestations and diagnosis of giant cell (temporal) arteritis. UpToDate. 2006. Temporal Artery Biopsy Best yield w/ 3-5cm samples bilaterally –94% Sensitive –Positive biopsy indicates poorer prognosis –Bilateral biopsy only increases sensitivity by 2-3%

10. Davies C et al. Temporal artery biopsy...Who needs one? Postgrad Med J. 2006; 82: 476- 478. Ray-Chaudhuri N et al. Effect of prior steroid treatment on temporal artery biopsy findings in giant cell arteritis. Br J Ophthalmol. 2002; 86: 530-532. Temporal Artery Biopsy Before or after treatment? –Treatment with steroids does not significantly alter biopsy results when samples are taken within 6 weeks. Small sample size (11 pts in 3 groups), but Risk of vision loss while waiting for biopsy is high Is a biopsy really necessary? –5%-9% false negative due to skip lesions –Risk of scalp necrosis, stroke, facial nerve injury, infection, bleeding, pain –Results rarely change treatment –If ≥ 3 ACR criteria are present without biopsy, biopsy is unnecessary –Biopsy is more helpful in atypical cases or when only 2 criteria are otherwise met

11. Hunder G. Clinical Manifestations and diagnosis of giant cell (temporal) arteritis. UpToDate. 2006. Associated Conditons Polymyalgia rheumatica –40-50% of patients w/ GCA also have PMR –15% of patients w/ PMR have GCA –Stiff, sore muscles in shoulders and hip girdle –Worse in the morning –ESR > 40mm/hr –Fever (10-15%) Thoracic aortic dissection Increased risk of cancer?

12. Arthritis Foundation 2001, Hoffman 2002, Jover 2001, Hunder 2006 Treatment of GCA Start glucocorticoids immediately –40-60 mg prednisone daily; Increase if suboptimal response –If visual loss, consider IV steroids –Maintain dose until sx remit and ESR and other labs return to normal, then taper 10% every 2 weeks as tolerated –If no response, perhaps it’s not GCA Methotrexate + glucocorticoids may prevent relapses and spare some steroid side effects, but results are not consistent Low-dose aspirin is recommended to reduce the risk of visual loss and CNS effects. Consider PPI to protect GI tract DEXA, Calcium and Vitamin D to protect against steroid- induced osteoporosis

13. Monitoring Mostly symptomatic Vision rarely decreases after treatment Increased risk of thoracic aortic aneurysm –17-fold increase, but still rare –Chest X-ray annually for 10 years

14. Lamprecht P. TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases. Autoimmunity Reviews. 2005; 4: 28-34. New Frontiers Diagnosis w/ MRI of temporal artery –Abnormal contrast enhancement –$$$, limited availability Further study of methotrexate use in GCA treatment needed TNF-α Inhibitors –Study underway

15. References Arthritis Foundation Primer on the Rheumatic Diseases. Edition 12. 2001. Davies C et al. Temporal artery biopsy... Who needs one? Postgrad Med J. 2006; 82: 476-478. Givre S, Van Stavern G. Amaurosis fugax: transient monocular and binocular vision loss. UpToDate. 2006. Hoffman G et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis & Rheumatism. 2002; 46: 1309-1318. Hunder G. Clinical Manifestations and diagnosis of giant cell (temporal) arteritis. UpToDate. 2006. Hunder G. Treatment of giant cell (temporal) arteritis. UpToDate. 2006. Image: Man with headache. www.arc.org.uk/about_arth/booklets/6047/6047.htm. 2006 Image: PMR pain. www.allaboutarthritis.com/.../PMR300X300.jpg. 2006. Image: Temporal artery. www.uveitis.org/medical/articles/case/gca.html. 2006 Image: Temporal artery biopsy. www.hopkinsmedicine.org/gec/studies/gca.html. 2006. Jover J et al. Combined Treatment of giant-cell arteritis with methotrexate and prednisone. Ann Intern Med. 2001; 134: 106-114. Kupersmith M et al. Visual performance in giant cell arteritis (temporal arteritis) after 1 year of therapy. Br J Ophthalmol. 1999; 83: 796-801 Lamprecht P. TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases. Autoimmunity Reviews. 2005; 4: 28-34. Ray-Chaudhuri N et al. Effect of prior steroid treatment on temporal artery biopsy findings in giant cell arteritis. Br J Ophthalmol. 2002; 86: 530-532.