Olabambo OgunbambiConsultant Rheumatologist
Hull Royal Infirmary
Giant Cell Arteritis&Polymyalgia
Rheumatica
EpidemiologyPathogenesisClinical FeaturesInvestigationsImagingMimicsTreatment
Giant cell arteritisPrimary systemic vasculitis medium/large vessels involves aorta & main branches
First described by Hutchinson 1890
Histological features described by Horton et al 1932
Epidemiology Most common vasculitis Europe/N americaIncidence increases with ageWomen affected 2-3 times more commonlyIncidence increases with latitude17/million in North American populations of
Scandinavian descent (over age 50)<12/million in South European populationsRare in blacks and Asians
Pathogenesis Still much uncertaintyFactors implicatedAgeGenetic factorsInfection(?) seasonal variation incidence
PathogenesisGenetic factorsHLA Association with HLA DRB1*04TNF microsatellite polymorphismsFunctional variant VEGF genePolymorphisms in genes for IL-13, NOS2,
TLR-4
Pathogenesis Both innate and adaptive immune factors implicatedPossible viral/other trigger stimulates monocyte activationActivated 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
Figure 1 Pathogenetic mechanisms operating in GCA
Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritisNat. Rev. Rheumatol. doi:10.1038/nrrheum.2012.97
Pathology
Affects extracranial branches of carotid artery
All layers of arterial wall involvedInflammatory lesions contain activated T cells dendritic cells macrophages giant cell cells
Pathology
Clinical featuresClassic 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
Clinical featuresJaw claudicationOccurs in 40-50% patients Highly specificNeeds to be distinguished from jaw pain ,
TMJ dysfunction and trismusOccasionally patients have intermittent
claudication affecting tongue, swallowing muscles
Temporal artery abnormalitiesDecreased or absent pulsesTendernessThickening Nodules Redness
Clinical featuresScalp tenderness -occurs in 30-50%
Worse with brushing/combing hair
Occasional patients develop scalp necrosis
Scalp necrosis in giant cell arteritis.
Mackie S L , and Pease C T Postgrad Med J 2013;89:284-292
Clinic featuresConstitutional 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
Ophthalmic complications
Frequency of occurrenceOpthalmology studies: 50% of patients
Rheumatology studies: 20-30% of patients
Ophthalmic complicationsAnterior ischemic optic neuritisMost common cause visual lossDue to interruption of flow in posterior
ciliary arteriesPresents as sudden painless visual lossMay present as mist in VF progressing to
blindness in 24-48 hrsUnilat visual loss may initially be missed
by patientMay progress to contralat eye in 1-10 days
Ophthalmic complicationsOther causes of visual lossCentral retinal art occlusion
Ischaemic retrobulbar neuropathy
Occipital infarction
Ophthalmic complicationsAmaurosis fugax -2-30% patients -Best clinical predictor of visual loss
Diplopia -ischemia of oculomotor nerve -occurs in 5-6% patient
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
Clinical featuresLarge vessel involvementDistal ischemiaLimb claudicationVascular bruitsMay present as PUOAortic involvement possibly more common
than recognised -risk of aortic rupture/dilatation
Clinical featuresNeurological manifestations
CVA
Mononeuropathies/polyneuropathies(rare)
Clinical featuresResp tract symptoms (often missed)CoughSore throatHoarseness
Clinical features Audiovestibular dysfunctionFacial painFacial swellingOdontogenic painGlossitisCarotidodynia
Investigations
Elevated ESR/CRP/PV
Inflammatory markers usually abnormal
Usual to check both CRP and ESR (or PV)
Investigations High fibrinogen/haptoglobinThrombocytosisAnemia of chronic diseaseElevated alkaline phosphataseAnticardiolipin antibodies
Temporal artery biopsyConsidered 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 treatmentOr soon as possible after starting treatment if required
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?
Temporal artery biopsy
Temporal artery biopsy
Temporal artery biopsy
Imaging High resolution colour doppler USCan visualise both lumen and vessel wallVessel wall features of presumed
inflammation- Seen as hypoechogenic mural thickening-”halo”Dependent on equipment, operatorNB “halo” reported in normal patient, PAN
Imaging Other features stenoses, occlusions
Sensitivity 88%, Specificity 78%
Precise role still not clearly defined
Figure 3 Ultrasonographical findings for GCA
Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritisNat. Rev. Rheumatol. doi:10.1038/nrrheum.2012.97
a & b = normal arteryc & d= temporal arteritis
MRICan 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?
C+D= Biopsy proven Giant Cell arteritis
Bley et al AJNR October 2007 28: 1722-1727
Bley T A et al. Rheumatology 2008;47:65-67
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).
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 arteriesClinical utility still unclear
Patient presenting with PUO
Mimics/differentialsCluster headacheCervical spondylosisSinus diseaseTemporomandibular
joint painEar problemsCTDOther systemic
vasculitides
Herpes zosterMigraineBasal skull lesionsInfiltrative retro
orbital lesionsTIA
Classification criteriaAge at onset>50yrsNew headacheTemporal artery abnormalityElevated ESR >50 (Westergren method)Abnormal artery biopsyThree or more features yieldSensitivity 93.5%Specificity 91.2% Limited applicability in daily practice
Predictors of neuro ophthalmic complications/positive TAB biopsy HistoryJaw claudicationDiplopiaPhysical examTA beadingTA prominenceTA tenderness
Treatment Recommended starting regimens
Uncomplicated GCA -no visual symptoms -no jaw claudicationStart Prednisolone 40-60mg
Treatment Complicated evolving visual loss or hx amaurosis fugax
IV methylpred 500mg-1g daily for three days
Then Prednisolone 60mg daily
Treatment Other issuesBone protection Bisphosphonate/calcium/vitamin D
supplementation
PPI
Aspirin 75mg daily
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
Monitoring Frequency: Suggested review at Weeks 0,
1, 3, 6 then months 3, 6, 9, 12 in the first year
Features:HeadachesJaw and tongue claudicationVisual symptoms.Vascular claudication of limbs, bruits,
pulsesBlood pressure Proximal pain and morning stiffness.Disability related to GCA.
Monitoring Full blood count, ESR/CRP, urea and
electrolytes, glucose
Every two yrs-CXR(?)
Bone mineral density
Management of relapseHeadache: 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
Steroid sparing agentsLimited evidenceConsider if recurrent relapses or difficulty
reducing steroid doseMethotrexate
Tocilizumab small case series/case reports of efficacy
Cyclophosphamide
Complications/prognosisGenerally runs self limited courseOverall survival similar to general
populationPermanent partial/complete loss of vision in
15-20%Inc risk CV events inc MI, CVA & PVD Risk aortic dilatation/aneurysmal rupture
Polymyalgia rheumaticaHighest incidence in Northern Europeans &
people of Scandinavian ancestry2-3 times more common than GCAOccurs in 50% patients with GCA5-30 % of patients with PMR may develop
GCASome pathogenetic similarity to GCA
Polymyalgia rheumaticaPresentation with pain and stiffness of
neck. Shoulder girdle and pelvic girdle usually at least 4 weeks duration
May be abrupt in onsetSymptoms and signs of systemic
inflammation Malaise, weight loss, low grade fever, swatsElevated CRP/ESR. Up to 20% may have normal ESR
Clinical featuresUp to 50% distal MSK featuresMild distal synovitis, bursitisOccasionally swelling/pitting edema of
hands, wristsCarpal tunnel syndromeSubjective weaknessConstitutional symptoms
Investigations Elevated CRP &/or ESR(PV)Nonspecific abnormalities in other testsAnemia, elevated alkaline phosphataseUS & MRI can demonstrate bursitis and
synovitisPET CT may demonstrate subclinical
vasculitis
Differentials Rheumatoid arthritis
Remitting Seronegative Symmetrical Synovitis with Pitting Edema
Multifocal MSK problems
Bone disease
Inflammatory myositis
Fibromyalgia
Hypothyroidism
Parkinson’s disease
PMR treatmentDramatically 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
Steroid sparingMostly conflicting and inconclusive data Options tried includeMethotrexateBiologics (anti-TNF agents)Azathioprine
Summary GCA & PMR are closely related disorders
affecting middle aged/older peopleUnknown cause but genetic and enviromental
factors influence pathogenesisGCA primarily affects aorta and extracranial
branchesIn GCA biopsy is important in confirming
diagnosisGC are cornerstone of treatmentSignificant associated morbiditySome patients have chronic course and require
GC for several yrs
Questions/comments?
QuestionJaw claudicationA. is pathognomonic of GCAB. is defined by pain on chewingC. signifies extensive involvement of
branches of the external carotid arteryD. is classified as an ischaemic feature of
GCAE. is never due to atherosclerosis alone
S. Mackie and C Pease. Postgrad Med J 2013;89:284-292
Question In the diagnosis of GCAA. The American College of Rheumatology criteria are useful diagnostic criteria in clinical practice.B. Ophthalmological evaluation is necessary in the
presence of visual manifestationsC. Pain on opening the mouth is one of the typical
ischaemic manifestations of GCAD. Jaw claudication is never caused by atherosclerosisE. Aortic imaging should be routinely performed
S. Mackie and C Pease. Postgrad Med J 2013;89:284-292
Thank you