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