FINDING A HIDDEN GIANTRheumatology Case Presentation

Registrar: JLeR Malherbe

Consultant: C Nel

Presenting History

Mrs HL is a 68 year old lady from Odendaalsrus

Reports that left radial pulse disappeared 4 months ago

More recently her right radial pulse also disappeared

She has bilateral arm claudication No calf claudication

Presenting History

No Headaches No Jaw claudication No Visual disturbances or loss of vision She has lost weight and feels chronically

tired Reports no fever or nightsweats She has palpitations Pain of shoulder and neck muscles. Worse in

morning. Can’t state a specific date of onset. Also reports pain around hips

Previous History

No Hypertension or Diabetes Only smoked for a few months when

younger No alcohol history Multiple DVT’s. After surgery. Using warfarin

for 12 years (episode early January INR suptherapeutic)

No History of miscarriages Family history of genetic hypercoagulable

state

Clinical Examination

Did not look acutely or chronically ill J- A- C- C- O- L- Respiratory exam normal Cardiac: Bigeminal rhythm, no murmers, no

CCF Abdominal: No HSM, no bruits Very weak radial pulse in right arm Absent radial pulse on left No skin changes or ulceration but both hands

cold

Clinical Examination

Femoral and leg pulses normal No pain over temporal arteries No temporal artery thickening Fundoscopy normal Neurological examination normal

Special Investigations

Duplex Doppler of arms Occlusion with ?thrombus of left axillary artery and severe stenosis of distal right axillary artery

Arteriogram rigth arm Complete right axillary artery stenosis at transition with brachial artery. Extensive collaterals. Complete stenosis of the radial artery at it’s origin. Interosseous and ulnar artery normal. Subclavian artery and aorta and other branches normal

Lupus anticoagulant positive

Picture so far

Considering Strong family history of hypercoagulability Patient history of DVT’s Episode of subtherapeutic INR (Although her

symptoms started before this) Positive Lupus Anticoagulant (Will need

repeat in 12 weeks)

Would be easy to attribute her presentation purely to the hypercoagulable state with arterial thrombosis/emboli

BUT.........

Rest of her Investigations

ESR > 90 (On multiple occasions) CXR, CT abdomen, PEF excluded TB and

occult malignancy CRP 66 No evidence of infection Hb 10.4, MCV 78.7 Plt 426, WCC 7.46, Eos

0.12 Fe 3.4, TF 1.9, TF sats 7%, Ferritin 231 RC Folate 529, VitB12 444

Albumin 28, Rest of Biochem (U/E, LFT, CMP normal)

Rest of her Investigations

ANCA Negative ANA Negative RF Negative ECHO/TEE Normal heart with no source

of emboli ECG Sinus rhythm with periods of

bigeminy

Thus

There’s clear evidence of systemic inflammation with anaemia of chronic inflammation and slightly low albumin

? Vasculitis Large vessel Old patient

?GIANT CELL ARTERITIS?

GCA Pathogenesis

Chronic vasculitis of large and medium size vessels Cranial branches of the arteries originating from the

aortic arch. Can be generalized. Almost never intracranial arteries

Etiology and pathogenesis unknown Increasing age, Genetic/Ethnic susceptibility (HLA-DR4),

Infectious agents (Parvo B19) Antigenic trigger Activation monocytes

Inflammatory cytokines (systemic symptoms) Infiltration of adventitia More cytokines, lymphocytes and macrophages chronic inflammation destruction, fibrosis, thrombosis

GCA History

Age > 50 Usually gradual onset. Can be abrupt Systemic complaints Fever, weigtloss, fatigue New headache in 2/3 Often temporal Jaw Claudication ½ (Specific) Visual symptoms Amaurosis fugax, AION,

Diplopia, Bitemporal hemianopia, Homonymous hemianopia, Visual hallucinations

Polymyalgia rheumatica 40 – 50% of GCA has PMR, 5% of PMR has GCA

CNS TIA, vertigo, hearing loss, and stroke

GCA History

3 – 15% subclavian/axillary arteries sufficiently narrowed to cause Arm Claudication Younger age of onset (66 vs 72) Less likely to have headache (14% vs 57%) Less likely to have temporal artery

involvement

Brack A; Martinez-Taboada V; Stanson A; Goronzy JJ; Weyand CM; Disease pattern in cranial and large-vessel giant cell arteritis: Arthritis Rheum 1999 Feb;42(2):311-7

GCA Examination

Thickened and tender temporal artery Absent temporal pulse Absent or diminished carotid, radial,

femoral or pedal pulses Bruits over major arteries Aortic regurgitation murmer heralds

development of ascending aorta aneurysm

GCA Diagnosis

Compatible clinical picture Laboratory

ESR Often > 100. Out of 941 biopsy proven GCA cases only 4 had normal ESR’s

CRP levels tend to parallel ESR. Anaemia of chronic inflammation, Reactive

thrombocytosis, Hypoalbuminaemia, Mildly elevated transaminases

Smetana GW; Shmerling RH; Does this patient have temporal arteritis? JAMA 2002 Jan 2;287(1):92-101.

GCA Diagnosis

Biopsy of temporal artery (or other accessible clinically involved artery) should be performed on all suspected cases of GCA

If artery not clinically abnormal at least 2cm. Shorter if visibly abnormal

Biopsy should be examined in multiple cuts Consider bilateral biopsy (unilateral misses 7.4 to

13%) Sensitivity of 85% in appropriate clinical setting In phenotype clinically involving only subclavian

or axillary artery sensitivity is 58%

Brack A; Martinez-Taboada V; Stanson A; Goronzy JJ; Weyand CM; Disease pattern in cranial and large-vessel giant cell arteritis: Arthritis Rheum 1999 Feb;42(2):311-7

Mrs HL’s Biopsy

Mrs HL’s Biopsy

GCA Pathology

Vasculitic lesions involve arteries in patchy fashion T lymphocytes and macrophages predominate Variable numbers of multinucleated giant cells (50% of

cases). Occasional plasma cells, neutrophils, and eosinophils.

Inflammation tends to occur mainly in media and internal elastic lamina (becomes fragmented)

Intimal thickening and thrombosis Based on above Mrs HL’s biopsy was reported as

being non-diagnostic for GCABUT.... In minimally involved arteries inflammation can be

localized to adventitia/external internal elastic lamina

GCA Diagnosis

MRI/MRA Especially suited for large vessels GCA Can demonstrate early arterial wall

oedema/thickening and inflammation Localize temporal artery disease Guiding

biopsy MR at Universitas does not have sufficient

resolution Conventional angiography

Only demonstrate lumen and not wall Tapering of subclavian/axillary artery is typical

GCA Diagnosis

Ultrasound Demostrate stenosis, occlusions Halo sign Highly dependant on operator sensitivity

in predicting positive biopsy only 40%

Considering the constellation of Mrs HL’s: clinical signs and special investigations Potential serious complications of untreated

GCA (Visual loss, limb ischaemia)

we decided to treat her as GIANT CELL ARTERITIS

Main differential diagnosis is Takayasu arteritis Age Arteries involved Renovascular hypertension is common Visual loss rare

Other vasculitides usually excluded on histology and vascular bed involvement

GCA Treatment

GCS is mainstay Prednisone 40 to 60mg dly Taper

slowly over a period of 9 to 12 months IV methylprednisone pulse if visual loss Low dose aspirin (plus PPI) Prophylaxis against osteoporosis ESR and CRP to monitor disease activity Remember complication of aortic

aneurysm

Conclusion

This is an unusual presentation of GCA Diagnosis confused by presence of a

history of thrombophilia Up to 18% of GCA may be positive for

Lupus Anticoagulant/ACLA/B2GP but there’s no statistical correlation with thrombotic ischaemic events. Congenital thrombophilia does not have a higher incidence in GCA

Espinosa G, Tàssies D, Font J, Muñoz-Rodríguez FJ, Cervera R, Ordinas A, Reverter JC, Ingelmo M; Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis: Semin Arthritis Rheum. 2001 Aug;31(1):12-20

References

1. Hunder GG; Pathogenesis of giant cell (temporal) arteritis; Clinical manifestations of giant cell (temporal) arteritis; Diagnosis of giant cell (temporal) arteritis; Treatment of giant cell (temporal) arteritis: UpToDate 17.3

2. Brack A; Martinez-Taboada V; Stanson A; Goronzy JJ; Weyand CM; Disease pattern in cranial and large-vessel giant cell arteritis: Arthritis Rheum 1999 Feb;42(2):311-7

3. Smetana GW; Shmerling RH; Does this patient have temporal arteritis? JAMA 2002 Jan 2;287(1):92-101

4. Espinosa G, Tàssies D, Font J, Muñoz-Rodríguez FJ, Cervera R, Ordinas A, Reverter JC, Ingelmo M; Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis: Semin Arthritis Rheum. 2001 Aug;31(1):12-20