Giant Cell Arteritis Diagnosis and Management Update

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Giant Cell ArteritisDiagnosis and Management
Update

• Roger Baer May 2008

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What is Giant Cell Arteritis?

• Ophthalmic Emergency

Sight Threatening and Treatable
.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 Kear
ns 1975
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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
gt50y.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
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Diagnostic Criteria
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

• Age (50y.o)
• New onset of localised headache
• Temporal artery tenderness or decreased temporal
  artery pulsation
• Elevated ESR (50mm/h)
• Positive TAB

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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• Opthalmologica August 2003 217239-259
• Sohan Singh Hayreh, Bridget Zimmerman

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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• Occult GCA
• 21.2 of patients with visual loss and a positive
  TAB had no other symptoms

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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• 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
  gt24.5mg/l

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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• 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
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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• 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
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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

• 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/h
A normal ESR does NOT rule out GCA
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Hayreh Zimmerman Study
Prospective study between 1973 and 1995 of 363
cases of suspected GCA at the University of Iowa
Hospitals and Clinics referred for TAB 106
positive (29), 257 negative (71)

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

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Hayreh Zimmerman Study
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
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Hayreh Zimmerman Study
Revised criteria for the diagnosis of
GCA Symptoms Signs Aches pains Flu-like
symptoms Headache Temporal artery
tenderness Jaw claudication Scalp
tenderness Malaise Pyrexia of unknown
origin Myalgia Anorexia ? weight loss Neck
pain
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Hayreh Zimmerman Study
Revised criteria for the diagnosis of
GCA Symptoms Signs Aches pains Flu-like
symptoms Headache Temporal artery
tenderness Jaw claudication Scalp
tenderness Malaise Pyrexia of unknown
origin Myalgia Anorexia ? weight loss Neck
pain
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Hayreh Zimmerman Study
Revised criteria for the diagnosis of
GCA Symptoms Signs Aches pains Flu-like
symptoms Headache Temporal artery
tenderness Jaw claudication Scalp
tenderness Malaise Pyrexia of unknown
origin Myalgia Anorexia ? weight loss Neck
pain
21.2 of patients with visual loss and a positive
TAB had no systemic symptoms or signs
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Hayreh Zimmerman Study
A few notes on Inflammatory Markers Erythrocyte
Sedimentation Rate (mm/h) (gt47mm/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) (gt1.9 units) ?
Easily automated, ? ?, slight increase with
age ? Value of gt1.90 equivalent to ESR
gt50mm/h CRP (C-Reactive Protein) (lt5 mg/l) (gt24.5
mg/l) ? More specific, sensitive, reproducible
and quantitative ? Responds more rapidly to
disease activity ? Not influenced by age, gender
or haematological factors
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Hayreh Zimmerman Study
Revised criteria for the diagnosis of
GCA Diagnostic Testing Inflammatory
markers Erythrocyte Sedimentation Rate Patients
with positive TAB (n106) 4 - 140mm/h Normal
individuals (n749) 1 - 59mm/h Specificity
and sensitivity of 92 using normal
range C-Reactive Protein Excellent sensitivity
(100), but specificity 80 ? Odds of having
GCA were 3.2 times greater with CRP gt24.5
mg/l compared with 24.5 mg/l
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Hayreh Zimmerman Study
Revised criteria for the diagnosis of GCA Other
Haematological Tests Full Blood Count
? Patients with GCA had a significantly higher
platelet count than the control group,
60.4 had a thrombocytosis (gt400 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)
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Hayreh Zimmerman Study

• Revised criteria for the diagnosis of GCA
• Temporal Artery Biopsy
• Skip lesions fact or fiction?
• In the HZ study, taking a 2.5cm biopsy with
  serial sectioning
• yielded a 100 positive TAB rate in GCA patients
• TABs for every patient?
• 1. GCA is a well-known masquerader
• 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

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Hayreh Zimmerman Study
Revised criteria for the diagnosis of GCA Doppler
Studies Value not proven Fluorescein
Angiography Good demonstration of attenuated flow
in posterior ciliary arteries
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Hayreh Zimmerman Study
Ophthalmic Manifestations of GCA Visual symptoms
in patients with positive TABs Visual
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 symptom Diplopia 6 Anterior
segment ischaemia Rare Cortical visual
loss Rare
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Hayreh Zimmerman Study
Conclusions Diagnostic Criteria

• Age (55y.o)
• Yes, check inflammatory markers
• Visual symptoms?
• No, consider other criteria
• Jaw claudication
• CRP gt24.5mg/l
• Neck pain
• ESR gt47mm/h
• Age 75y.o
• Temporal Artery Biospy

?GCA if ?CRP
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Hayreh Zimmerman Study
Revised criteria for treatment of GCA Immediate
high dose corticosteroids Across-the-board
1mg/kg prednisolone is now outmoded Dose should
be tailored to extent or potential for visual
loss High 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
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Hayreh Zimmerman Study
Revised criteria for treatment of GCA Immediate
high dose corticosteroids Across-the-board
1mg/kg prednisolone is now outmoded Dose should
be tailored to extent or potential for visual
loss In 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 fugax Complete
or severe visual loss Signs of bilateral
involvement
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Hayreh Zimmerman Study

• Revised criteria for treatment of GCA
• Tapering steroids
• 1. 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
• Review Every 2-3 weeks until dose 40mg
  Every 4-6 weeks until maintenance dose
  established Then every 3 months

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Hayreh Zimmerman Study
Revised criteria for treatment of GCA Tapering
steroids In 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
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Hayreh Zimmerman Study
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
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Hayreh Zimmerman Study
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