Giant Cell Arteritis - Acute Myocardial Infarction

Giant Cell ArteritisDiagnosis and Management Update

Roger Baer May 2008

What is Giant Cell Arteritis?

Ophthalmic Emergency

‘….GCA ranks as the prime medical emergency in ophthalmology, there being no other disease in which prevention of blindness depends so much on prompt recognition and early treatment…’

Kearns 1975

Sight Threatening and Treatable

What is Giant Cell Arteritis?Granulomatous, necrotising inflammation of medium and large arteries, with a predilection for the superficial temporal, ophthalmic, posterior ciliary and proximal part of the vertebral arteries. The aetiology is unknown.

Incidence of ~18 cases per 100,000 population >50y.o

Histologically characterised by:

● Thickening of the intima, narrowing of the lumen and disruption of the internal elastic lamina

● Inflammatory cell infiltrate● Skip lesions

60-80% of patients with GCA will have a +ve TAB

Diagnostic Criteria

1. Age (≥50y.o)2. New onset of localised headache3. Temporal artery tenderness or decreased temporal

artery pulsation4. Elevated ESR (≥50mm/h)5. Positive TAB

Prior to this study, the ‘gold standard’ for diagnosing GCA was considered to be the guidelines set by the The American College of Rheumatology in 1990

‘A patient shall be classified as having GCA if 3 of the following 5 criteria are met’:

Hayreh & Zimmerman Study

Opthalmologica August 2003; 217:239-259Sohan Singh Hayreh, Bridget Zimmerman

Prospective study between 1973 and 1995 of 363 cases of suspected GCA at the University of Iowa Hospitals and Clinics referred for TAB106 positive (29%), 257 negative (71%)


Occult GCA

21.2% of patients with visual loss and a positive TAB had no other symptoms



•Criteria Missing from ACR Guidelines

•Likelihood of a positive TAB were:• ● 9.0 times greater if associated with jaw claudication• ● 3.4 times greater if associated with neck pain• ● 3.2 times greater if associated with CRP >24.5mg/l



•Headache & Scalp Tenderness

•55.7% of patients with a positive TAB complained of a ‘new onset of localised headache’


But…..so did 45.5% of patients with a negative TAB

Scalp tenderness was similarly unreliable


•Clinically Abnormal Temporal Artery

•19.8% of patients with a positive TAB had temporal artery tenderness or decreased temporal artery pulsation


But…..so did 12.8% of patients with a negative TAB


•Elevated ESR

•Whilst the ACR guidelines advocated an ESR of ≥50mm/h, this study showed a presenting ESR in patients with a positive biopsy of 4-140mm/h.


And…..in those with a negative biopsy of 2-155mm/hA normal ESR does NOT rule out GCA


•Conclusion

•Reliance on the ACR Guidelines is likely to result in both false-negative and false-positive diagnoses of Giant Cell Arthritis



Revised criteria for the diagnosis of GCA

Age, sex and ethnicity● The youngest patient in this study was 56 y.o● The ratio of women to men was 2.6 : 1● Caucasians are more susceptible than other races



Symptoms & SignsAches & pains Flu-like symptomsHeadache Temporal artery tendernessJaw claudication Scalp tendernessMalaise Pyrexia of unknown originMyalgia Anorexia weight lossNeck pain







21.2% of patients with visual loss and a positive TAB had no systemic symptoms or signs


A few notes on Inflammatory Markers

Erythrocyte Sedimentation Rate (mm/h) (>47mm/h)● What is normal? Age in years divided by 2 ♂

Age in years +10 divided by 2 ♀● Hayreh & Zimmerman suggest normal range 1 - 59mm/h

Plasma Viscosity (1.5 – 1.72 units) (>1.9 units)● Easily automated, ♂ = ♀, slight increase with age● Value of >1.90 equivalent to ESR >50mm/h

CRP (C-Reactive Protein) (<5 mg/l) (>24.5 mg/l)● More specific, sensitive, reproducible and quantitative● Responds more rapidly to disease activity● Not influenced by age, gender or haematological factors



Diagnostic Testing – Inflammatory markersErythrocyte Sedimentation Rate

Patients with positive TAB (n=106) 4 - 140mm/hNormal individuals (n=749) 1 - 59mm/hSpecificity and sensitivity of 92% using ‘normal range’

C-Reactive ProteinExcellent sensitivity (100%), but specificity ~80%

● Odds of having GCA were 3.2 times greater with CRP >24.5 mg/l compared with ≤ 24.5 mg/l



Other Haematological TestsFull Blood Count ● Patients with GCA had a significantly higher platelet count than the control group, 60.4% had a thrombocytosis

(>400 x 103/μl) ● GCA patients also tended to have a higher white cell count

and lower haemoglobin than the control group

Conclusion: ESR, CRP and FBC are highly useful in diagnosing GCA. Used together ESR and CRP provide the best specificity (97%)



Temporal Artery Biopsy‘Skip lesions’ – fact or fiction?In the H&Z study, taking a 2.5cm biopsy with serial sectioningyielded a 100% positive TAB rate in GCA patients

TABs for every patient?1. GCA is a well-known masquerader2. The risks of steroid-related systemic complications

Low yields (3-4%) from bilateral TABs suggests unjustified

Steroids therapy does NOT significantly alter pick-up rate*** DO NOT WITHOLD STEROIDS TO WAIT FOR TAB ***



Doppler StudiesValue not proven

Fluorescein AngiographyGood demonstration of attenuated flow in posteriorciliary arteries


Ophthalmic Manifestations of GCA

Visual symptoms in patients with positive TABsVisual loss 98%

Arteritic anterior ischaemic optic neuropathy 76.4%Posterior ischaemic optic neuropathy 5.7%Central retinal artery occlusion 12.2%Cilioretinal artery occlusion 21.2%Cotton wool spots 33.0%

Amaurosis fugax 31% - useful early symptomDiplopia 6%Anterior segment ischaemia RareCortical visual loss Rare


Conclusions – Diagnostic Criteria

Age (≥55y.o) Yes, check inflammatory markers

Visual symptoms? No, consider other criteria:

Jaw claudicationCRP >24.5mg/lNeck painESR >47mm/hAge ≥75y.o

Temporal Artery Biospy

∆GCA if ↑CRP


Revised criteria for treatment of GCA

Immediate high dose corticosteroidsAcross-the-board 1mg/kg prednisolone is now outmoded Dose should be tailored to extent or potential for visual lossHigh doses indicated: History of amaurosis fugax

Complete or severe visual loss Signs of bilateral involvement Marked systemic symptoms, CRP or ESR Progression on lower dose Poor response in CRP or ESR



Immediate high dose corticosteroidsAcross-the-board 1mg/kg prednisolone is now outmoded Dose should be tailored to extent or potential for visual lossIn the Hayreh & Zimmerman Study:

● Median starting dose 80mg/day (40% ≥ 100mg/day)● IV megadose steroid was no more effective than oral● Current advice to give one megadose IV only if:

History of amaurosis fugaxComplete or severe visual lossSigns of bilateral involvement



Tapering steroids1. Tapering of steroid therapy not started until both ESR and

CRP reach low, stable levels (normally after 2-3 weeks of high dose steroids).

2. Aim then to maintain these low levels on the lowest possible dose of steroids

3. Review: Every 2-3 weeks until dose ≤40mg Every 4-6 weeks until maintenance dose

established Then every 3 months



Tapering steroidsIn the Hayreh & Zimmerman Study: ● Median time to maintenance dose 48.7 months ● Median maintenance dose 7mg/day ● Only 10 out of 145 patients got off steroids ● Most patients will therefore require indefinite steroids ● Maintenance doses of steroids present a low risk of morbidity, though calcium and vitamin D would be advised ● Limited evidence for use of steroid-sparing agents ● Limited evidence benefit from aspirin


Prognosis

● 4% of patients with visual loss due to GCA experienced an improvement in vision with high-dose steroids

● 4% of patients suffered further deterioration in vision after starting high-dose steroids (though none after 5 days)

● High-dose steroids are effective in preventing further visual loss in 96% of GCA patients


Conclusions – Treatment

Start high dose steroids immediately (this will not affect any subsequent TAB)

Consider IV megadose steroids if amaurosis fugax, compete or severe visual loss or bilateral

CRP and ESR are reliable and sensitive parameters for monitoring activity and tapering steroids

Anticipate an indefinite course of steroids

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Giant Cell Arteritis - Acute Myocardial Infarction