An elderly man presented with headache - HKGShkgs.org/IHGM/IHGM_wl_chow27Sept2013.pdf · 1 14 Anterior ischemic optic neuropathy due to occlusion of the posterior ciliary arteries

An elderly man presented with headache

Dr Chow Wan Lung (Yan Chai Hospital)

( supervisor) Hung SC

27th September 2013 (IGHM)

Patient- Mr. C Part 1

•Mr. C, 67 y. o. male

•presented with a 2 weeks history of persistent dull headache over the vertex and bi-temporal areas, associated symptoms include malaise and fatigue.


• Negative history:

- Non throbbing / periodic / cyclical in nature

- No history of fever

- No history of early morning headache associated with vomiting

- No history of blurring of vision/ diplopia / amaurosis fugas / visual loss

- No history of jaw/ tongue claudication / tooth ache

- Denied muscular pain/ joint stiffness/focal weakness

- No history of chest pain/ limb claudication / abdominal pain

- No history of recent un-intentional weight loss /cough/ respiratory

- symptoms

- No history recent head injury

- No history alcohol abuse / substance withdrawal


• Past medical history revealed:

1) A treated pulmonary Tuberculosis over 20 years ago.

2) Type II Diabetes mellitus

3) A treated Peptic ulcer disease over 10 years ago

• Chronic medications:

Diamicon 80 MG om

Zocor 20 MG om

Aspirin 80 mg om

Pepcidine 40 mg om


Note : differential diagnosis of headache are:

• 1) Migraine , with or without aura

• 2) tension-type headache

• 3) cluster headache

• 4) headache associated with head/neck trauma, including chronic post-traumatic headache.

• 5) headache attributed to cranial/ cervical vascular disorder. i.e. ischaemia, ICH, SAH, GCA, artery dissection, cerebral venous sinus thrombosis.

• 6) Hydrocephalus, idiopathic intracranial hypertension, neoplasm.


• 7) headache attributed to substance or its withdrawal.

• 8) Headache attributed to disorder of homeostasis – hypoxia, hypercapnia, metabolic disturbance, fasting, arterial hypertension, hypertensive encephalopathy.

• 9)Headache or facial pain attributed to disorder to cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cranial structures.

• 10) headache attributed to psychiatric disorder.

• 11) Cranial neuralgia- i.e. Trigeminal neuralgia.


•Clinical examination:

BP 130/61 mmHg

P 60 bpm

Temp 36.6 ‘c.

Weight : 68 kg Height : 1.6 m BMI: 27

MMSE 29/30, GDS 2

CNS: Gait Normal.

No focal focal neurological deficit


• CVS: Equal pulses felt bilaterally. Peripheral pulses were

present.

No AR / murmur heard. No carotid bruit.

• Abdomen : No abdominal bruit.

• Oral cavity- no sign of tongue/ lip necrosis. Dental carries.

• Sinus: no tenderness.

• Scalp: Reduce pulsation felt over the Right temporal artery.

My patient- Mr. C

• Ophthalmologic exam :

VA R=6/8 ; L=6/8

EOM – normal. No pain felt upon eye movement

Fundoscopy : Normal optic disc , no cotton wool spot,

normal retinal vessels seen.

• Other systems : no positive finding

Investigations:

Blood results: Hb 13.8, ESR 92


• Right Temporal artery biopsy :Findings:

- featuring intimal thickening and calcification.

- Inflammatory cells found in the intma and internal elastic lamina focally

- No giant cell identified.

Pathological diagnosis: Consistent with arteritis , could be in keeping with Giant cell arteries.

Note:- 1) Biopsy segment of temporal artery - 3 cm in length.

2) Performed by surgical team 26 days after the empirical Prednisolone

therapy had begun.


•Treatment:

Prednisolone 50 mg daily PO.

( Prednisolone was given as an empirical treatment prior the Temporal artery biopsy.)

Part 2 : Giant cell arteritis (GCA)

•A granulomatous arteritis of the large and medium-vessels. ( i.e. Aorta and its branches)

•Holding a particular tropism to the extra-cranial branches of the carotid arteries ,especially the superficial temporal artery.

•Occurs almost exclusively in patients >50 years of age.

•Etiology : unknown.

Giant cell arteritis (GCA) Part 2

•The inflammatory process starts in the adventitia and may lead to vascular lumen narrowing or non-thrombotic , complete occlusion secondary to proliferation of the intima ( intimal hyperplasia).

• Ischaemic complications developed in tissues irrigated by these vessels.

• It is a critically ischaemic disease and should be treated as a medical emergency.

Classic features of giant cell arteritis

1) Headache

2) Claudication of the jaw and tongue

3) Loss of vision in one eye (up to a fifth of patients)

4) Fever

5) Myalgia

6) Weight loss

7) Anorexia

8) Fatigue


Complications:

1) Disease related:

• Early: Neuro-ischaemic complications.

i.e. vision loss or stroke.

• Late : Inflammatory aorta-arteritis- development of

aortic aneurysm , aortic dissection.

2) Glucocorticosteroid related: weight gain, bruising

osteoporosis and fractures, diabetes,

cataract, hypertension, GI, neuropsychiatric,

accelerated atherosclerosis and

hyperlipidaemia.

Vasculature Complications

Affected Arteries Possible Complications

Ophthalmic Blindness

Subclavian Absent pulse

Renal Hypertension

Coronary Angina pectoris

Carotid Stroke

Vertebral Dizziness, Stroke

Iliac Claudication

Mesenteric Abdominal pain


Prognosis:

• 1) If vision has not been affected-outlook is excellent.

• 2) If vision loss occur- usually permanent.

• 3) If aorta or nearby branches affected- prognosis may be worse, because these blood vessels may enlarged or even rupture.

The American College of Rheumatology classification criteria for giant cell arteritis

Patients should meet three of the followings:

•Age ≥ 50 years.

•New onset of localized headache.

•Tenderness or decreased pulse in the temporal artery.

•Erythrocyte sedimentation rate ≥ 50 mm/h.

•A positive biopsy of the temporal artery showing mononuclear cell infiltrates or a granulomatous process with multinucleate giant cells.

Common Signs & Symptoms of GCA

Royal College of Physicians. (2010, Aug). Diagnosis and management of giant cell arteritis.

The Guidelines of GCA


The Guidelines- Continued


The Guidelines- Continued


Pathway for management of GCA


Recommended regimens for glucocorticosteroidtreatment


Recommended regimens for glucocorticosteroidtreatment


Classic symptoms of GCA part 3

•Classic symptoms such as headache, jaw claudication and visual changes, make the diagnosis relatively easy.

However! part 3

atypical presentations are often missed or attributed to another cause.

Important for clinicians to be aware of the diverse presentations to avoid unnecessary investigations and prevent complications such as visual loss, myocardial ischemia, cerebrovascular accident, and death.

Part 3 :Discussion on GCA

1) “up to 40 % of patients have an atypcial presentation”

Moltyaner Y. &Tenenbaum J. (1996). Temporal arteritis a: a review and case history. J Fan Pract, 43, 294-300.

2) “Many histologically negative individuals were nevertheless clinically diagnosed and manages as GCA”

Habbia Saedon et al. (Oct 2012). JRSM Short Rep, 3(10), 73

3) “Giant Cell Arteritis can occur in the absence of a raised ESR”

Elisabeth De Smit et al. (2013). BMJ, 346, 122

Discussion on GCA part3

4) a) “Imaging techniques for giant cell arteritis:

Ultrasound and MRI” Reinhard M et al. (Mar 2009). Z Rheumatod, 68(2), 108-16

b) “Use of Color Duplex ultrasound to diagnosed

giant cell arteritis”Butteriss A et al . (2004). The British journal of radiology, 77, 607-609

5) “Anti-Interleukin 6 receptor therpay as rescue

treatment for giant cell arteritis”

Beyer et al. (Oct 2011). Annals of Rheumatic diseases, 1874-1875

1) Atypical presentation of GCA part3

‣ As many as 40% of presentations may be atypical

Moltyaner Y.& Tenenbaum J.(1996).Temporal arteritis: a review and case history. J Fam Pract,43,294–300.

The American College of Rheumatology classification criteria for giant cell arteritis

Patients should meet three of the followings:

•Age ≥ 50 years

•New onset of localized headache

•Tenderness or decreased pulse in the temporal artery

•Erythrocyte sedimentation rate ≥ 50 mm/h

•A positive biopsy of the temporal artery showing mononuclear cell infiltrates or a granulomatous process with multinucleate giant cells

The American College of Rheumatology 1990 criteria for the classification of GCA

Criteria for the classification of giant cell (temporal) arteritis were developed by comparing214 patients who had this disease with 593 patients with other forms of vasculitis:

1)For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%.

2)A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%.

Hunder GC et al. (1990, Aug). Arthritis Rheum, 33(8), 1122-8.

Initial manifestation and clinical findings in 100 patients with temporal arteritis

Features

No. of patients

DescriptionAt presentationFinding at diagnosis

Headache 32 68 Continuous generalized or temporal pain

Polymyalgia rheumatica

25 39 Pain in the neck, shoulder girdle or pelvic girdle; prolonged muscle stiffness upon waking

Fever 15 42 Elevated body temperature (e.g., 39ºC)


Initial manifestation- Continued

Features

No. of patients

DescriptionAt presentation Finding at diagnosis

Visual symptoms without loss of vision

7 30 Amaurosis fugax (precedes permanent loss of vision in 44% of patients), diplopia or eye pain

Weakness, malaise or fatigue

5 40 May be the only presenting symptoms

Tenderness over arteries

5 27 The frontal and parietal branches of the superficial temporal arteries may be thickened, nodular, erythematous and tender


Initial manifestation- Continued

Features

No. of patients

DescriptionAt presentation Finding at diagnosis

Weight loss or anorexia

2 50 May be mistaken for malignant disease

Claudication of the jaw 2 45 Pain while chewing due to ischemia of the muscles of the jaw

Permanent loss of vision

1 14 Anterior ischemic optic neuropathy due to occlusion of the posterior ciliary arteries

Claudication of the tongue

1 6 Pain due to ischemia of the muscles controlling the tongue


Atypical presentation of GCA part 3

Though loss of vision due to ischaemic optic neuritis is a well-known complication of GCA, 21.2 % of patients with GCA and visual symptoms have no other cranial or systemic manifestations

Melson Mret al. (2007). The diagnosis of giant cell arteritis. Rev Neurol Dis, 4, 128-42.

15 % of patients may present with fever aloneCantini F et al. (2009). Diagnosis and treatment of Giant cell arteritis.. Drugs Aging, 25,

281-97

Atypical presentation of GCA-Tongue necrosis part 3

Case Report 1:

- 80 y.o. male - Sudden massive swelling of tongue- Swelling rapidly progressed to a complete necrosis within

few days.- unilateral blindness developed despite prompt treatment

confirmed Dx of temporal arteritis.- However the biopsy of left and right temporal artery,

remained non-specific for the disease. - Dx based on the unusual clinical presentation

Cikes A et al. (Jul 2001). Vasa,30(3), 222-4


•Tongue necrosis - a complication of temporal arteritis

Case Report 2: - 79 y.o. patient - had tongue necrosis 3 hours after ingestion of 2 mg of

ergotamine tartrate - basis for Dx of temporal arteritis Possible existence triggering factors in 11 of the published

cases was analyzed- In 7 of these cases, ingestion of ergotamine derivative had

taken place .Llorente pendas S et. (Oct 1994). Oral Surg Oral Med Oral Pathol, 78(4), 448-51


Case Report 3:

- Tongue necrosis with partial visual field loss in a patient with temporal arteritis

- Complications were probably released by ergotaminetartrate administered because of a presumably migrainoid headache.

Barfoed CP. & Bretlau P. (Sep- Oct 1984). Acta Otolaryngol, 98(3-4), 380-4

Atypical presentation of GCA-Scalp necrosis

- Scalp necrosis associated with GCA first described in 1940s

- It represent a :

Severity marker. Higher mean age at diagnosis

Elevated risk of vision loss and tongue gangrene

Overall higher mortality

Maidana DE. ( Jul 2011).World Journal, 11, 1313-5


Case Study:•70 y. o. male •with a painful 6 x 6 cm necrotic ulceration in the left temporparietal region of the scalp•Smaller satellite lesion with identical characteristic in occipital area•Both lesions rapidly developed over 6 weeks•Further complain of jaw claudication•However, no fever, malaise, headache or visual loss

Maidana DE. (Jul 2011). World Journal, 11, 1313-5


• Blood tests: mild thrombocytosis, ESR was 30 mm/h

• Temporal artery biopsy : multinucleated giant cells at the media-intima border



Note : The differential diagnosis of scalp ulceration in older patients

include:1)herpes zoster2)irritant contact dematitis3)ulcerated skin tumors4)post-irradiation ulcers5)microbial infections6)pyoderma gangrenosum7)giant cell arteritis

Overall mortality rate in GCA with scalp necrosis varies in different studies and range from 23.7% to 38%.


Atypical presentation of GCA-Cotton-wool spots

Case Study:- 71 y. o. woman - reduced vision in right eye- Additional symptoms : headache , scalp tenderness, pain

in jaw when chewing- Fundoscopy: multiple cotton-wool spots in both eyes.

More markedly in right eye- ESR- 90 mm/h - Biopsy of the temporal artery confirmed GCA

Elisabeth D. et al. (Oct 2012). Canadian Medical Association Journal. (impact factor: 8.22).


- Despite high-dose IV steroids treatment, vision deteriorated in both eyes

- Subsequently vision improved in left eye but remained poor in right eye

- Systemic symptoms resolved, ESR dropped to 25mm/h

- Over the next 2 months , the cotton –wool spots resolved completely



Note :

1 ) Differential diagnosis of cotton-wool spots :

• hypertension,

• diabetes,

• HIV infection

• rheumatologic disease

2) Cotton-wool spots are associated with retinal ischaemia and represent localised accumulation of axoplasmin debris. Their pathognesis is a topic of debates.


Ophthalmic artery inflammation produces

•visual blurring

•diplopia

•usually precede visual loss (sudden, painless, usually permanent partial or complete)

Atypical presentation of GCA-posterior circulation stroke

Reportedly the cause of first-ever stroke in 0.11% of patients

Wiszniewska M. (2007).Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis, 24,226-30


Case Study:

-85 y. o. man

-Difficulty walking, dizziness and double vision lasted for one week

-Previously experienced several weeks of temporal headache and weight loss

-Abnormal findings: upbeat nystagmus, gaze palsy when looking to right and gait ataxia

-Diffusion-weighted MRI: multiple, small, acute and subacute infarcts in the pons, cerebellar hemispheres and occipital lobes

-Computed tomography (CT) angiogram: bilateral concentric thickening of the walls of the vertebral arteries extracranially with irregular, concentric stenoses of these arteries from the subclavian artery to the upper cervical vertebrae .

Wiszniewska M. (2007). Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis, 24,226-30


Case Study- Continued:

-Treatment: IV heparin, followed by warfarin for the presumed dissection. -After 4 weeks in hospital, he was discharged to a stroke rehabilitation facility-6 weeks after being discharged from hospital, patient was readmitted with a decreased level of consciousness, dysarthria and worsening ataxia

Wiszniewska M. (2007). Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis,24,226-30


- A diffusion-weighted MRI showed:• new infarcts in the pons, cerebellum and midbrain

- A magnetic resonance angiogram showed: a)severely diminished blood flow in the basilar artery, as well as extensive multifocal areas of diminished flow within the vertebral arteries

b)a new, moderately severe, area of stenosis within the petrous portion of his left internal carotid artery wasevident

Wiszniewska M. (2007). Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis, 24, 226-30



Cerebral angiography performed within 24 hours of the start of treatment showed:

• occlusions of the vertebral arteries bilaterally and filling of the basilar artery coming only from collateral vessels

•Irregular beading and stenoses were seen in the superficial temporal arteries, which is consistent with giant cell arteritis.

Wiszniewska M. (2007). Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis,24,226-30



Rapid progression of changes in the large vessels led to the consideration of vasculitis as a possible diagnosis

- ESR- 30 mm/h

- C-reactive protein level was 25 mg/L

- Hb level was normal

- Laboratory markers of systemic vasculitis were negative

- Treatment with methylprednisolone (1 g/d intravenously) was initiated



Biopsy of superficial temporal arteries 48 hours after the start of steroid therapy showed:

•the classical pattern of multinucleated giant cells, fragmentation of the internal elastic lamina and lymphocytic infiltrate consistent with GCA



-Patient’s level of consciousness continued to deteriorate

-despite aggressive therapy with high doses of IV steroids, he died of respiratory arrest the following day

-The respiratory arrest was presumed to be secondary to brainstem ischemia

-The author conceded “Because the diagnosis of giant cell arteritis was not initially considered in our patient, we missed the significance of his weight loss and headache, and an erythrocyte sedimentation rate was not initially ordered.”



Red flags for the diagnosis of giant cell arteritis in patients

presenting with stroke:

• Headache or tenderness of the temporal artery

• Constitutional symptoms such as fever, malaise or weight loss

• Bilateral occlusions or severe stenosis of the vertebral arteries

• Imaging studies showing involvement of only the extracranial vessels and not the intracranial segments


Atypical presentation of GCA-Absence of a raised ESR part 4

1) “ESR can be normal in giant cell arteritis and polymyalgia rheumatica.”

- In these diseases up to 22.5 % of patient can have a normal ESR

Helliwell T. (2012). BMJ, 344, e1408


2) Giant cell temporal arteritis with a normal erythrocyte sedimentation rate.

a) Elevated ESR has a sensitivity of only 76% to 86 %.

Low ESR may be seen in : Polycythaemia, CHF or anti-inflammatory medications

b) CRP : higher sensitivity ( 97.5 % ) , but there have been cases with a normal CRP and GCA revealed on biopsy.

Advantage : not influenced by age or other hematological factors.

“ No laboratory tests have perfect sensitivity for GCA, reliance on them can result in delay to diagnosis, resulting in substantial morbidity and mortality.”

Ciccarelli M. (Feb 2009). Am J Emerg Med, 27(2), 255.e1-3


3) ” Are steroids alone sufficient for the treatment of giant cell arteritis ?”

Numerous retrospective and prospective studies have shown that a strong inflammatory response characterized by raised levels of acute-phase reactants and by constitutional symptoms such as fever and weight loss areinversely correlated with the risks of developing ischaemic events.

Low inflammatory response and the presence of previous ischaemic events including amaurosis fugax and unilateral visual loss, have been shown to be significantly associated with the risk of developing new ischaemic complications.

Pipitone N et al. (Apr 2005). Best Pract Res Clin Rheumatol, 19(2), 277-92


The reason for the “ protective role” of a stronginflammatory response against GCA related ischaemic complication remain to be established.

IL-6 – a potent inducer of hepatic acute-phase reactants might promote angiogenesis and thus protect against ischaemic complications in GCA, but it is conceivable that other inflammatory mediators could also play a role.

Pipitone N et al. (Apr 2005). Best Pract Res Clin Rheumatol, 19(2), 277-92

Temporal artery biopsy in GCA-retrospective audit part 5

• A retrospective audit of all patients undergoing TAB at a single teaching hospital between 2005 and 2011, identified from the histopathology database.

• 153 TAB were performed (mean age 70.8 years, men : women = 3:2, 110 Caucasian: 43 Asian). 32 biopsies were positive for GCA and 121 were negative.

• In total, 68 (61%) of 112 negative TAB patients were clinically diagnosed with GCA despite histological findings (P < 0.001).

• 9 out of 153 biopsies were non-arterial.

• Histologically positive TAB patients were of higher mean age (77.1 [95% CI 74.5–79.7] versus 69.1 [95% CI 66.7–71.6]; P < 0.001) and had a higher erythrocyte sedimentation rate (ESR) (60 [95% CI 46.1–73.9] versus 39.8 [95% CI 34.2–45.3]; P < 0.01)] than those with negative histology.

Habiba Saedon et al. (Oct 2012). JRSM Short Rep, 3(10), 73


Length of arterial biopsy (NB: 9 of the 121 histologically negative biopsies were excluded from this analysis due to non-arterial biopsy)

• Length of superficial temporal artery biopsied was a mean of 10.9 mm for ophthalmologists and 9.5 mm for vascular surgeons (P = NS; Mann–Whitney U test)

• Preoperative CRP, gender and ethnicity were not significantly associated with histological arteritis.

Habiba Saedon et al. (Oct 2012). JRSM Short Rep, 3(10),73


Note:

• Preoperative steroids therapy were commenced for 125 (82%) of the individuals subjected to TAB for a presumptive diagnosis of GCA. 9 % did not receive preoperative steroids and in a further 9%, there was no recorded data relating to steroid therapy.

• Postoperatively, a clinical diagnosis of GCA was made in all individuals found to exhibit histological arteritis. All of these patients received steroids postoperatively.



Arteritis, n = 32 (histological)

Non-arteritis, n = 112 (histological)

P value

Age-years (95%CI) 77.1 (74.5–79.7) 69.1 (66.7–71.6) P < 0.001

Gender (M/F) 21/11 69/52 P = NS

Mean length (mm) 10.5 9.4 P = NS

Ethnicity (Asian/Caucasian)

9/23 34/87 P = NS

ESR – mm/hour (95%CI)

60 (46.1–73.9) 39.8 (34.2–45.3) P < 0.01

CRP – mmol/L (95%CI)

41.9 (26.2–57.6) 31.2 (23.9–38.5) P = NS



The percentage of positive biopsies / length of the biopsies were:

1) Saedon et al. JRSM Short Rep. 2012 October; 3(10): 73

the percentage of positive biopsies was 29%

2) Mahr et al.'s study, temporal artery biopsy for diagnosing giant cell arteritis: the longer the better? Ann Rheum Dis 2006;65:826-8

1520 patients who had undergone TAB and found only 15% had histological evidence of GCA

19 % - < 5 mm 71-79% - 6-20 mm 89% - > 20 mm Therefore a recommendation of greater that 5 mm should be obtain



3) E. Ypsilantis al.’s study BKS volume 98 issue 11 Nov 2011.

Positivity rate of 24.8 per cent, biopsies with post-fixation length at least 0.7 cm

Double than those with specimen smaller than 0.7 cm (12.9 per cent).

4) Cantini al.’s Diagnosis and treatment of giant cell arteritis. Drugs Aging 2008;25:281–97

Recommended that a specimen of at least 1.5 cm in length be obtained if the temporal artery is tender and indurated on palpation.

A longer specimen should be obtained if the artery is not tender and appears normal.

Contralateral biopsy should be performed if the first side is normal

However, 10% of biopsies in patients with giant cell arteritis remain negative with this approach.



Point to note:

•A high proportion of histologically negative individuals were nevertheless diagnosed and managed as GCA on clinical grounds


Interpretation of Temporal artery specimen in GCA part 5

• Pitfalls can confuse a pathologist from correctly diagnosing giant cell arteritis from a temporal artery biopsy

1) Up to 40 % of positive biopsies show diffuse lymphocytic infiltrate without evidence of granulomatous inflammation or giant cells

2) Fragmentation and fraying of the internal elastic lamina is a constant feature of all aging arteries

Alone not indicative of active or healed arteritis

There must be an inflammatory cells infiltrate to diagnose temporal arteritis

3) healed temporal arteritis ( because patient on long term corticosteroids) can still be diagnosed, since it is characterized by:

intimal fibrosis,

medial scarring and

eccentric destruction of the internal elastic lamina

Corticosteroid therapy does not normalized the affected artery

Sterling W. (2002) Rheumatology Secrets. Hanley & Belfus 2nd Edition, 210

Could radiological tests aid the diagnosis?

Part 6Colour duplex Ultrasound: Advantages:

1) Rapid, simple and non-invasive method that has several applications2) Equivocal cases or when patients refuse temporal artery biopsy a

normal ultrasound may obviate the need for biopsy or unnecessary treatment

3) Used to identify abnormal segments before biopsy to reduce the risk of a false negative result

Radiological signs: 1) Transverse duplex ultrasound image showing the “halo” effect due to

mural edema2) Longitudinal duplex ultrasound image through the superficial temporal

artery showing irregular lumenal stenosis and mural thickening

Butteriss at al. (2004). British Journal of Radiology, 77, 607-609

Could radiological tests aid the diagnosis ?Part 6

1) Puechal et al. Superficial temporal Doppler flow studies in suspected giant cell arteritis : validation of diagnostic score. Arthritis rheum 1994;37 (Temporal, ophthalmic and facial arteries )

- Specificity of 80% and a sensitivity of 77% (Using temporal artery biopsy as the gold standard)

2) Schmidt et al. Colour duplex ultrasounography in the diagnosis of temporal arteritis. N Engl J med 1997;337:1336-42 (Temporal arteries – found echolucent halo / stenosis / occlusion)

In 28 of the 30 patients with GCA:- 93% specificity and sensitivity for diagnosing GCA- No halos were identified in the 82 patients without temporal arteritis- 6 (7%) had stenoses or occlusions



3) Stammler et al. Value of colour-coded duplex ultrasound in patients with polymyalgia theumatica without signs of temporal arteritis. Stsh Med wochenscgr 2000; 125:1250-6

(Echolucent halo at temporal artery)

- 100% sensitive and 80% specific for temporal arteritis,

(using temporal artery biopsy as the gold standard)



However ….

1) Venz et al have demonstrated an indistinguishable halo in the temporal arteries of patients without GCA, showing that it is not completely specific.

2) Stenosis and occlusion were not diagnostically useful, because these findings are common among the elderly or patient with macrovasculae disease.

3) Demand a high-quality Doppler ultrasound equipment ,a liner probe with a frequency higher than 8 Hz and a sonographer experienced in vascular ultrasound.



•Therefore, further study is necessary to determine if duplex ultrasound alone is sensitive and specific enough to diagnose GCA without recourse to temporal artery biopsy.


Anti-interleukin 6 receptor therapy as rescue treatment for GCA Part 7

• Treatment options for GCA are limited.

• Systemic corticosteroids are the main treatment, but relapse are common and often necessitate high cumulative doses of glucocorticoids.

• If patient is not responding or to taper the systemic steroids, one can add methotrexate as an adjuvant or maintenance therapy.

• Cytokines blockade with infliximab and etanercept has been tried with conflicting results.

• Temporal artery biopsy samples show enhanced IL-6 production and IL-6 levels generally correlate with disease activity

• To investigate the effects of Tocilizumab, a humanized IL-6 receptor antibody, in patient with refractory GCA

Beyer et al.(2011). Ann Rheum Dis, 70, 1874-1875


Case Report 1: 79 y. o. male with GCA Despite excellent initial response to coticosteroids, he could not taper

prednisolone to dose less than 30 mg /day Methotrexate was contraindicated due to chronic renal failure No clinical improvement with azathioprine.

Case Report 2: 71 y. o. famale with GCA experience relapse while on corticosteroid tapering regimen MRA show subclavian artery involvement Thickening of the femoral artery vessel walls with halo sign Methotrexate was not tolerated due to gastrointestinal side effect

Beyer et al. (2011). Ann Rheum Dis, 70, 1874-1875


Treatment for both cases:

• Tocilizumab infusion ( 8 mg/kg/ body weight) every month for 6 months

•Tapering of glucocorticoid during the induction phase

•After the induction therpay with tocilizumab, all patients were on prednisolone dosages below 7.5mg/day.



Discussion:

• The rapid clinical and serological response is stimulating.

• However there remains uncertainties:

1) Patient might represent a subgroup of GCA patient with high systemic inflammatory response and involvement of the aorta and its main branches-Takayasu-like features

2) IL-6 shows angiogenic activity and might have positive effects on neovascularisation to compensate for vessel occulsion in GCA.

3) Suppressing the acute phase response with the general feeling of sickness may mask persistent vascular inflammation.


ConclusionsKey points• Given the wide spectrum of presentations of giant cell arteritis,

physicians need to be equally familiar with both typical and atypical presentations

• Most important piece of information is the entire clinical presentations

• One must use the entire clincal picture as well as ancillary test for guidance

• Ancillary tests cannot rule out GCA i.e. ESR, Temproal artery biopsy• The presenting manifestation of giant cell arteritis may be stroke

Giant cell arteritis should be considered as a cause of stroke in patients with “red flags”.

• Concentric, long-segment, increased thickening of the arterial wall, particularly extracranially, on computed tomography angiography may indicate giant cell arteritis

Conclusions

Pitfalls in diagnosis of GCA:

• 1) cardinal ischaemic features of GCA( jaw/tongue claudication and visual symptoms), may go unrecognised or be attributed to other conditions especially if not accompanied by headache.

• 2) Patients at highest risk of neuro-ophthalmic complications do not always mount high-inflammatory responses.

• 3) PMR is also associated with GCA in 50% of the cases at presentation.

• 4) An acute phase response can occur in other setting.

References

• Beyer et al. (Oct 2011). Annals of Rheumatic diseases, 1874-1875

• Butteriss A et al . (2004). The British journal of radiology, 77, 607-609

• Cantini F et al. (2009). Diagnosis and treatment of Giant cell arteritis.. Drugs Aging, 25, 281-97

• Ciccarelli M. (Feb 2009). Am J Emerg Med, 27(2), 255.e1-3

• Cikes A et al. (Jul 2001). Vasa,30(3), 222-4

• Elisabeth De Smit et al. (2013). BMJ, 346, 122

• Elisabeth D. et al. (Oct 2012). Canadian Medical Association Journal. (impact factor: 8.22).

• European Journal of Dermatology. (Dec 1999). Vol 9. No. 8. 652-3

• Habbia Saedon et al. (Oct 2012). JRSM Short Rep, 3(10), 73

• Helliwell T. (2012). BMJ, 344, e1408

• Hunder GC et al. (1990, Aug). Arthritis Rheum, 33(8), 1122-8

References

Indian Journal of Dermatology. (2013 Jul- Aug), 58 (4):328

Jocelyn et al. (Mar 2011). CMAJ,183(5), E301–E305

Llorente pendas S et. (Oct 1994). Oral Surg Oral Med Oral Pathol, 78(4), 448-51

Maidana DE. ( Jul 2011).World Journal, 11, 1313-5

Melson Mret al. (2007). The diagnosis of giant cell arteritis. Rev Neurol Dis, 4, 128-42.

Moltyaner Y. &Tenenbaum J. (1996). Temporal arteritis a: a review and case history. J Fan Pract, 43, 294-300

Pipitone N et al. (Apr 2005). Best Pract Res Clin Rheumatol, 19(2), 277-92 The Scientific World Journal. (2011) 11, 1313–1315

Reinhard M et al. (Mar 2009). Z Rheumatod, 68(2), 108-16

Royal College of Physicians. (2010, Aug). Diagnosis and management of giant cell arteritis

Sterling W. (2002) Rheumatology Secrets. Hanley & Belfus 2nd Edition, 210

Wiszniewska M. (2007).Giant cell arteritis as a cause of first-ever stroke. Cerebrovasc Dis, 24,226-30

Documents

An elderly man presented with headache - HKGShkgs.org/IHGM/IHGM_wl_chow27Sept2013.pdf · 1 14 Anterior ischemic optic neuropathy due to occlusion of the posterior ciliary arteries