Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica

Giant cell arteritis is a granulomatous vasculitis of large and medium arteries, particularly the temporal artery, that frequently coexists with polymyalgia rheumatica, an inflammatory condition causing pain and stiffness in the shoulder and pelvic girdles, both predominantly affecting individuals over 50 years of age.

Exam domain	One-glance essentials
Definition / diagnosis	GCA is granulomatous vasculitis of the aorta and major branches, especially cranial arteries ^[1] PMR is inflammatory shoulder/hip-girdle pain and stiffness; the disorders frequently coexist ^[2]
Epidemiology / risks	*GCA occurs almost exclusively at age ≥ 50*; female predominance, and it is less common in Asians ^[1]^[2] Any PMR patient remains at risk of concurrent or subsequent GCA ^[2]
Core mechanism	Dendritic/T-cell/macrophage activation → granulomas and elastic-lamina destruction → intimal hyperplasia → arterial ischaemia ^[2] Ophthalmic artery involvement causes arteritic anterior ischaemic optic neuropathy ^[3]
Clinical picture	*New temporal headache, scalp tenderness, jaw claudication and amaurosis fugax/visual loss* ^[1] PMR: bilateral shoulder/hip pain, morning stiffness and reduced active but preserved passive movement ^[2]
Investigations	ESR/CRP, CBC and LFT; temporal-artery ultrasound halo sign and biopsy support GCA ^[1]^[2] Biopsy is segmental: skip lesions can cause false negatives; PMR usually has normal CK and negative autoantibodies ^[2]
Management	*Suspected GCA with visual symptoms: start high-dose steroid immediately—do not await biopsy* ^[1]^[3] Sight-threatening disease needs IV methylprednisolone; PMR usually responds to much lower-dose prednisolone ^[2]
Complications	Permanent visual loss, often preceded by amaurosis fugax; treatment chiefly protects the other eye ^[3] Stroke and aortic aneurysm/dissection/stenosis require long-term surveillance ^[2]
Prevention / follow-up	Baseline/long-term aortic surveillance and repeated screening for GCA symptoms in PMR ^[2] With prolonged steroids: calcium/vitamin D, bisphosphonate when indicated, glucose/BP and infection monitoring ^[2]
Exam traps	*Treat → investigate → confirm when vision is threatened; biopsy can remain informative after steroid initiation ^[2]^[3] GCA and PMR overlap but steroid doses are not interchangeable*; PMR pain is not true myopathic weakness ^[2]

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (GCA/PMR, pp.87–88) ^[2] Senior notes: Ryan Ho Rheumatology.pdf (GCA and PMR, pp.95–96) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (GCA visual complications and management, pp.1158–1162)

Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are closely related inflammatory conditions that frequently co-exist and may represent clinical subsets of a single disease process ^[1]^[2].

Giant Cell Arteritis (GCA) — also known as temporal arteritis or cranial arteritis — is an idiopathic autoimmune, granulomatous arteritis of the aorta and its major branches ^[1]^[2]^[3]. The name tells you the pathology: "giant cell" = multinucleated giant cells seen on histology; "arteritis" = inflammation of arteries. It is the commonest form of primary vasculitis ^[1]^[2].
Polymyalgia Rheumatica (PMR) — "poly" = many, "myalgia" = muscle pain, "rheumatica" = relating to rheumatic/joint stiffness — is a clinical syndrome of sudden onset of severe pain and stiffness of shoulders and pelvic girdle (limb girdle pattern) with markedly raised inflammatory markers ^[4]. It is NOT a vasculitis per se, but reflects periarticular/synovial inflammation in the proximal joints.

Key Relationship: GCA and PMR

GCA and PMR often co-exist and may represent clinical subsets of a single disease process. However, treatment of these conditions is not the same. PMR patients require lower doses of steroid ^[1]. Approximately 40–50% of GCA patients have PMR, while conversely ~10–15% of PMR patients have underlying GCA ^[2]^[3]^[4].

Why is GCA a Medical Emergency?

GCA is a potentially sight-threatening disease — untreated, it causes permanent visual loss in ~15–20% of patients via arteritic anterior ischaemic optic neuropathy (AAION). The importance of timely diagnosis and treatment cannot be overstated: once vision is lost, it is almost always irreversible ^[5]^[6].

Epidemiology

Parameter	Detail
Incidence	~20/100,000 person-years in those > 50 years ^[1]^[2]
Sex	Female : Male = 2:1 ^[1]^[2]
Age	Predominantly the elderly; almost never occurs before age 50; mean onset age ~70–76 years ^[2]^[3]^[7]
Ethnicity	Most common in Northern Europeans/Scandinavians; unusual in Asians (lower incidence in Hong Kong Chinese populations compared to Caucasians) ^[4]^[7]
Distinction	The MOST common form of systemic vasculitis affecting people ≥ 50 years old ^[3]

Parameter	Detail
Incidence	Varies widely by ethnicity; less common in Asians ^[4]
Sex	F >> M (2–3:1) ^[4]
Age	Peak onset 70–80 years; rarely < 50 years ^[4]
Association	~50% of GCA patients have PMR; ~10–15% of PMR patients develop or have concurrent GCA ^[2]^[4]

Risk Factor	Mechanism / Comment
Ageing	MOST important risk factor — incidence rises steadily after age 50, peaking between 70–79 years ^[3]. Ageing-related immunosenescence and vascular remodeling predispose to aberrant immune activation in vessel walls
Female sex	2–3× increased risk; possibly related to hormonal/immunological sex differences ^[1]^[2]
Northern European / Scandinavian descent	Highest incidence globally; genetic founder effects. Lower in Asians (relevant to Hong Kong exam context)
Genetics	*HLA-DRB104 alleles (same HLA association as RA — both T-cell–mediated diseases); non-HLA gene polymorphisms such as PTPN22** (involved in T-cell signalling threshold) ^[3]
Smoking	Independent risk factor for GCA ^[3]
Prior/concurrent PMR	PMR is a risk factor for developing GCA and vice versa
Seasonal/infectious triggers	Epidemiological data suggest possible seasonal clustering, possibly triggered by infections (e.g., Mycoplasma, parvovirus B19, VZV), though no definitive causal pathogen has been identified

Anatomy and Function

Understanding the anatomy is crucial because GCA preferentially targets specific vessels, and the pattern of involvement explains virtually every symptom.

GCA is a large vessel vasculitis primarily affecting:

Aorta and its major branches (subclavian, axillary, vertebral, carotid arteries)
Extracranial branches of the carotid artery, especially:
- Superficial temporal artery (most commonly affected → hence "temporal arteritis")
- Occipital artery
- Ophthalmic artery and its branches:
  - Posterior ciliary arteries → supply the optic nerve head
  - Central retinal artery → supplies inner retina
- External carotid artery → maxillary artery → masseteric branch (supplies masseter and temporalis muscles)
Vertebral arteries → posterior circulation

GCA preferentially affects arteries with well-developed internal elastic lamina and vasa vasorum. The internal elastic lamina is the primary target of the granulomatous inflammatory process. Intracranial arteries are relatively spared because they lose their internal elastic lamina and vasa vasorum after penetrating the dura — this is why GCA causes extracranial but rarely intracranial strokes.

Artery	Clinical Consequence of Occlusion
Superficial temporal artery	Temporal headache, scalp tenderness, visible/palpable artery abnormalities
Posterior ciliary arteries (branches of ophthalmic artery)	Arteritic anterior ischaemic optic neuropathy (AAION) → sudden painless monocular blindness ^[6]^[7]
Central retinal artery	Central retinal artery occlusion (CRAO) → sudden severe monocular vision loss with cherry red spot ^[8]
Maxillary/masseteric artery (branch of ECA)	Jaw claudication — ischaemia of masseter/temporalis muscles during chewing ^[2]^[3]
Lingual artery (branch of ECA)	Tongue claudication — rare but described ^[9]
Vertebral/basilar arteries	Posterior circulation stroke ^[2]
Aorta	Aortic aneurysm, dissection, stenosis ^[2]^[4]
Subclavian/axillary arteries	Limb claudication, asymmetric BP, absent pulses ^[9]

PMR involves periarticular synovial structures (bursae, tendon sheaths, synovial membranes) around the:

Shoulder girdle — glenohumeral joint, subacromial/subdeltoid bursae, biceps tendon sheath
Hip girdle — hip joint, trochanteric bursae, iliopsoas bursae
Cervical spine

This is NOT primarily a muscular disease despite the name — the "myalgia" comes from periarticular inflammation perceived as muscle pain. Imaging (MRI, PET-CT, ultrasound) shows bursitis and tenosynovitis rather than myositis.

Etiology and Pathophysiology

The exact cause remains unknown. GCA/PMR is presumed to be autoimmune based on:

Response to corticosteroids
Association with HLA-DRB1*04
T-cell–mediated granulomatous inflammation
Possible infectious triggers (molecular mimicry)

This is a T-cell and macrophage-driven granulomatous vasculitis centred on the arterial wall:

Key Pathological Steps Explained

Initiation — Adventitial dendritic cell activation: Dendritic cells in the vessel wall become activated and recruit T cells and monocytes to the vessel wall ^[3]. The adventitia (outermost layer) contains resident dendritic cells that serve as sentinels. In GCA, these become inappropriately activated — possibly by ageing-related damage-associated molecular patterns (DAMPs) or infectious molecular mimics.
T-cell–mediated inflammation: CD4+ T cells infiltrate the arterial wall and polarise into Th1 (producing IFN-γ) and Th17 (producing IL-17) subsets. IFN-γ is the master cytokine driving macrophage activation.
Granuloma formation: Macrophages then form multinucleated giant cells ^[3] — these are the histological hallmark. Giant cells cluster at the media–intima junction, specifically at the fragmented internal elastic lamina.
Vessel wall destruction: Giant cells secrete metalloproteinases (MMPs) and reactive oxygen species (ROS) compromising the structural integrity of the vessels ^[3]. MMPs digest the elastic fibres of the media, while ROS cause oxidative damage.
Intimal proliferation: Intimal proliferation leads to reduced blood flow resulting in partial or complete ischaemia ^[3]. This is the crucial step that causes clinical manifestations — the lumen narrows concentrically due to myofibroblast proliferation and extracellular matrix deposition in the intima.
Thrombosis: The damaged, narrowed vessel is prothrombotic → thrombosis due to vessel wall thickening ^[6] → end-organ ischaemia (optic nerve, brain, muscles).
Systemic inflammation: IL-6 is the dominant systemic cytokine in GCA → drives the acute phase response (hepatic production of CRP, fibrinogen, hepcidin → anaemia of chronic disease) and the constitutional symptoms.

Why IL-6 Matters — The Tocilizumab Connection

IL-6 is the key cytokine driving both systemic inflammation and the acute phase response in GCA. This is why anti-IL-6 therapy (tocilizumab) has emerged as a steroid-sparing agent — it directly blocks the pathogenic cytokine. The GiACTA trial (2017) showed tocilizumab significantly reduces relapse rates and cumulative steroid exposure in GCA.

Temporal artery biopsy shows ^[2]^[6]:

Panarteritis: inflammation affecting all three layers (adventitia, media, intima)
Mixed inflammatory infiltrate: lymphocytes, plasma cells, neutrophils
Multinucleated giant cells: clustered at the internal elastic lamina (present in ~50–80% of positive biopsies; their absence does NOT exclude GCA)
Fragmentation and disruption of the internal elastic lamina (best seen on elastic van Gieson stain)
Intimal hyperplasia: concentric thickening narrowing the lumen
± Fibrinoid necrosis of the media

Skip Lesions

GCA inflammation is patchy (segmental) — "skip lesions" occur along the temporal artery. This means a biopsy may be falsely negative if the sampled segment is uninvolved. This is why an adequate length biopsy (≥ 1 cm, ideally 2 cm) and bilateral biopsy (if first side negative) are recommended ^[6]^[2].

PMR pathophysiology is less well understood than GCA, but involves:

Subclinical synovitis and bursitis: Ultrasound and PET-CT studies show inflammation in subacromial/subdeltoid bursae, biceps tendon sheaths, hip joint synovium, and trochanteric bursae
Cytokine-mediated: Similar IL-6–dominant cytokine profile to GCA but without the full granulomatous arterial wall inflammation
No true myositis: Muscle enzymes (CK) are normal — the pain is referred from periarticular structures
Shared pathogenesis with GCA: The same Th1/Th17 immune dysregulation likely underlies both, with PMR representing a "forme fruste" (incomplete form) of the same disease spectrum

Classification

GCA is classified as a large vessel vasculitis (LVV) alongside Takayasu arteritis ^[10]:

Feature	GCA	Takayasu Arteritis
Age	≥ 50 years (almost never < 50)	< 50 years (typically 10–40)
Sex	F:M = 2:1	F:M = 9:1
Ethnicity	Northern European predominance	Asian predominance (most relevant for HK exams)
Vessels	Temporal and cranial arteries + aorta	Aorta and major branches (less cranial involvement)
Histology	Granulomatous (both)	Granulomatous (both)
Distinguishing feature	Temporal artery involvement, jaw claudication, visual loss	"Pulseless disease", limb claudication, HTN (renal artery stenosis)

Mnemonic: "BATHE" ^[2]

Criterion	Detail
B — Biopsy evidence	Necrotizing arteritis, predominant mononuclear cells / multinucleated giant cells (granuloma)
A — Age ≥ 50 years	Almost never occurs before 50
T — Tenderness / decreased pulsation of temporal artery	On clinical examination
H — New onset localised Headache	Typically temporal
E — ESR > 50 mm/hr	Characteristically very high

Sensitivity 93.5%, Specificity 91.2% for classification purposes. Note: these are classification criteria (for research/categorisation), not strictly diagnostic criteria — clinical judgement remains paramount.

The updated 2022 criteria use a weighted scoring system (≥ 6 points classifies as GCA) and incorporate imaging:

Mandatory entry criterion: Age ≥ 50 years
Clinical criteria: morning stiffness in shoulders/hips, jaw/tongue claudication, temporal artery abnormality (tenderness, decreased pulse), new headache
Laboratory criteria: ESR ≥ 50 or CRP ≥ 10 mg/L
Imaging/biopsy criteria: positive temporal artery biopsy, halo sign on temporal artery ultrasound, bilateral axillary artery involvement on imaging

Subtype	Description
Cranial GCA	Classic temporal arteritis with headache, jaw claudication, visual symptoms — involvement of superficial temporal, ophthalmic, occipital arteries
Large vessel GCA (LV-GCA)	Involvement of aorta and its major branches (subclavian, axillary, etc.) — may present with limb claudication, asymmetric BP, aortic aneurysm — overlaps with Takayasu-like picture
Overlap	Many patients have both cranial and extra-cranial large vessel involvement ^[5]

High Yield: GCA with Large Vessel Involvement

The GC interactive tutorial emphasises understanding that GCA can have both cranial AND extra-cranial large vessel involvement ^[5]. Don't think of GCA as only a "temporal artery disease" — it is fundamentally an aortitis that can affect any branch of the aorta. Aortic aneurysm (especially thoracic) occurs in ~10–20% of GCA patients and may present years later.

Clinical Features

From the GC lecture slide on headache, a comprehensive breakdown of presenting features in GCA ^[9]:

Feature	Frequency
Headache	72%
Polymyalgia rheumatica	58%
Malaise, fatigue	56%
Jaw pain during chewing (jaw claudication)	40%
Fever	35%
Cough	17%
Neuropathy	14%
Sore throat, dysphagia	11%
Amaurosis fugax	10%
Permanent visual loss	8% (ophthalmological complications, mostly optic neuropathy, ~20%)
Limb claudication	8%
TIA/Stroke	7%
Neuro-otological disorder	7%
Scintillating scotoma	5%
Tongue claudication	4%
Depression	3%
Double vision, diplopia	2%
Myelopathy	0.6%

Symptoms (with Pathophysiological Basis)

New onset intense throbbing headache ^[2]^[6], typically bitemporal ^[9]
Why? Inflammation of the superficial temporal artery and other cranial arteries stimulates perivascular nociceptive nerve fibres (trigeminal sensory afferents that innervate the adventitia) → pain. The temporal artery runs in the superficial temporal fascia, making it accessible to palpation and explaining the localised headache.
Character: typically described as severe, persistent, throbbing; may be unilateral or bilateral
Often associated with scalp tenderness — painful to comb hair, wear a hat, or rest head on pillow ^[6]^[7]

Pain when chewing or talking ^[2]^[6] — 越咬越痛 (the more you chew, the worse it gets) ^[2]
Why? Ischaemia of masseter and temporalis muscles due to occlusion/stenosis of the maxillary artery (branch of the external carotid artery) ^[2]^[6]. "Claudication" = pain with use that improves with rest (Latin: "claudicare" = to limp). The masseter has high metabolic demand during chewing → ischaemic pain when demand exceeds supply through narrowed arteries.
Pathognomonic for GCA ^[6] — highest positive likelihood ratio of any symptom for GCA (LR+ ~4.2)

Pain in the tongue during sustained talking or eating
Why? Ischaemia of tongue muscles via lingual artery involvement (branch of ECA)
Rare but very specific for GCA ^[9]

Amaurosis fugax (10%) ^[9]: transient monocular visual loss (like a "curtain coming down"), lasting seconds to minutes, then resolving
- Why? Transient ischaemia of the optic nerve or retina via vasospasm or microemboli from inflamed temporal/ophthalmic arteries — a warning sign of impending permanent visual loss
Permanent visual loss (8%, ophthalmological complications ~20%) ^[9]: typically sudden, painless, severe monocular loss of vision
- Why? Arteritic anterior ischaemic optic neuropathy (AAION) — the posterior ciliary arteries (branches of the ophthalmic artery) that supply the optic nerve head become occluded by vasculitis-induced thrombosis → infarction of the optic nerve head ^[6]^[7]
- May be preceded by amaurosis fugax (prodromal) ^[7]
- If untreated, the contralateral eye is at high risk (bilateral blindness can occur within days to weeks)
Diplopia (2%) ^[9]: due to ischaemia of extraocular muscle cranial nerves (CN III, IV, VI) or the muscles themselves
Scintillating scotoma (5%) ^[9]: may mimic migraine aura; due to cortical or retinal ischaemia

Visual Symptoms = Emergency

For visual symptoms, do NOT wait for biopsy result → start empirical steroids ^[2]. Amaurosis fugax is a warning — once permanent visual loss occurs, it is almost always irreversible. The goal is to save vision of the other eye and prevent brainstem stroke ^[2].

Pain and morning stiffness in bilateral shoulder and hip girdles ^[2]^[4]^[6]
Sudden onset of severe pain + stiffness of shoulders and pelvic girdle (limb girdle pattern) ^[4]
Classically severe morning stiffness — marked 'gel' phenomenon with increased stiffness with rest ^[4]
May also involve the neck and torso ^[3]
Why? Periarticular synovial inflammation (bursitis, tenosynovitis) of the shoulder and hip girdle joints. The "gel phenomenon" occurs because during rest, inflammatory exudate accumulates in periarticular tissues → stiffness that improves with movement as the fluid redistributes.

Fever (35%) — usually low grade ^[2]^[4]^[9], but can occasionally be high and cause fever of unknown origin (FUO)
Malaise, fatigue (56%) ^[9]
Weight loss ^[2]^[4]
Night sweats ^[4]
Why? Systemic IL-6 and other pro-inflammatory cytokines act on the hypothalamus (fever), suppress appetite (weight loss), and cause generalised malaise

Cough (17%) ^[9]
Sore throat, dysphagia (11%) ^[9]
Why? Vasculitis of pharyngeal/laryngeal arteries → mucosal ischaemia and inflammation; also possibly central cough reflex sensitisation

Neuropathy (14%) ^[9]: mononeuropathy or mononeuritis multiplex due to vasa nervorum ischaemia
TIA/Stroke (7%) ^[9]: typically posterior circulation (vertebrobasilar territory) due to vertebral artery involvement; less commonly carotid territory
Neuro-otological disorder (7%) ^[9]: hearing loss, vertigo, tinnitus — due to ischaemia of vestibulocochlear arterial supply
Myelopathy (0.6%) ^[9]: very rare; spinal cord ischaemia from vertebral/anterior spinal artery involvement
Depression (3%) ^[9]: likely multifactorial (chronic illness, cytokine effects on CNS)

Limb claudication ^[9]: pain in upper (more common) or lower limbs with exertion
Why? Large vessel GCA affecting subclavian/axillary arteries → reduced blood flow to upper limbs. Functionally similar to peripheral arterial disease but caused by vasculitis rather than atherosclerosis.

Signs (with Pathophysiological Basis)

Tender, thickened, non-pulsatile temporal artery ^[2]^[6]
Prominent, tortuous temporal artery ^[6]
Decreased pulsation ^[2]
Why? The inflammatory infiltrate causes vessel wall thickening and oedema → the artery becomes palpably enlarged and tender. Luminal narrowing/thrombosis → loss of pulsation. The temporal artery is superficial (runs over the temporal fascia anterior to the ear) → easily examined.

Scalp tenderness ^[1]^[2] — particularly on combing hair ^[7]
Why? Ischaemia of the scalp via occluded superficial temporal and occipital arteries; also direct inflammation of subcutaneous arteries

Decreased pulses, discrepant BP, ± bruits ^[2]^[4]
Asymmetric BP — measure both arm BP! ^[2]
Why? Large vessel GCA causing stenosis/occlusion of subclavian or axillary arteries → differential blood pressure between arms (> 15 mmHg difference is significant). Bruits over carotid, subclavian, axillary arteries indicate turbulent flow through stenosed segments.

Very pale ('chalky white'), swollen optic disc with peripapillary haemorrhages ^[4]^[7]
± Central/branch retinal artery occlusion (CRAO/BRAO), cotton wool spots at posterior pole ^[7]
Why? Infarction of the optic nerve head → the disc becomes massively oedematous and pale (chalky white = more pale than NAION because it is a complete arteritic occlusion of the posterior ciliary arteries rather than partial). Peripapillary haemorrhages result from venous congestion secondary to the disc swelling.
RAPD (relative afferent pupillary defect) positive ^[7]: the afferent limb of the pupillary light reflex is damaged → the affected eye's pupil dilates (rather than constricts) when light is swung from the unaffected to the affected eye
Altitudinal visual field defect ^[7]: typically superior or inferior half of the visual field is lost, reflecting the watershed zone of posterior ciliary artery supply to the optic nerve head

Decreased active range of motion (AROM) with preserved passive range of motion (PROM) ^[4]
Classically shoulder abduction ROM < 90° ^[4]
Why? The pain from bursitis/tenosynovitis limits the patient's willingness and ability to move actively (AROM reduced), but the joints themselves are structurally normal so passive movement by the examiner is preserved (PROM normal). This distinguishes PMR from arthritis (where PROM would also be limited) and from true myopathy (where weakness, not pain, limits movement).
May have muscle tenderness on palpation ^[4]

Feature	GCA	PMR
Core symptoms	Headache, jaw claudication, visual symptoms	Bilateral shoulder/hip girdle pain and stiffness
Morning stiffness	May have (if co-existing PMR)	Marked — hallmark feature
Constitutional	Fever, weight loss, malaise	Similar but may be less prominent
Visual threat	YES — medical emergency	No (unless underlying GCA)
Key signs	Temporal artery tenderness/thickening, loss of pulse	↓AROM with preserved PROM
Inflammatory markers	Very high ESR (often > 100)	Elevated ESR/CRP (but less extreme)
Steroid dose needed	High dose (1–2 mg/kg/day prednisolone)	Low dose (10–15 mg/day prednisolone) sufficient ^[4]

High Yield Summary

GCA:

Granulomatous arteritis of aorta and its major branches; commonest form of primary vasculitis ^[1]^[2]
Almost never < 50 years; F:M = 2:1; less common in Asians
Pathophysiology: Adventitial dendritic cells activate → T cell and macrophage recruitment → granuloma formation → MMP/ROS → elastic lamina destruction → intimal hyperplasia → luminal narrowing → ischaemia
Key symptoms: New temporal headache (72%), jaw claudication (40%, pathognomonic), amaurosis fugax/visual loss, PMR (58%), constitutional symptoms
Key signs: Tender, non-pulsatile temporal artery; scalp tenderness; chalky white swollen disc (AAION); asymmetric BP
ACR criteria (BATHE): Biopsy + Age ≥ 50 + Temporal artery tenderness + Headache + ESR > 50 (≥ 3/5)
EMERGENCY: Do NOT wait for biopsy if visual symptoms — start empirical steroids immediately
GCA and PMR often co-exist but treatment is NOT the same — PMR requires lower doses of steroid

PMR:

Sudden onset bilateral shoulder/hip girdle pain and severe morning stiffness
↓AROM with preserved PROM; shoulder abduction < 90°
Elevated ESR/CRP with negative autoantibodies
Responds to low-dose prednisolone (10–15 mg/day); usually self-limiting (50% stop steroids after 1–2 years)

Active Recall - GCA and PMR

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf, p87–88 ^[2] Senior notes: Maksim Medicine Notes.pdf, p311 (Temporal arteritis / GCA section) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p1158–1160 ^[4] Senior notes: Ryan Ho Rheumatology.pdf, p95–96 ^[5] Lecture slides: GC_Interactive tutorial (Rheum case 1) student copy.pdf, p1 ^[6] Senior notes: Ryan Ho Neurology.pdf, p65 ^[7] Senior notes: Ryan Ho Opthalmology.pdf, p91–94 ^[8] Senior notes: Ryan Ho Opthalmology.pdf, p65 ^[9] Lecture slides: GC 082. Severe headache_headache and neuralgia; neuro-imaging I.pdf, p33 ^[10] Senior notes: Maksim Medicine Notes.pdf, p332

Differential Diagnosis of GCA and PMR

The differential diagnosis of GCA and PMR must be approached from two angles: (1) the presenting symptom complex that mimics GCA (headache ± visual loss ± constitutional symptoms in an elderly patient), and (2) the presenting symptom complex that mimics PMR (bilateral proximal girdle pain/stiffness with raised inflammatory markers). These are distinct clinical presentations that have overlapping but different differential lists.

Core Principle for DDx

Diagnosis of primary headache needs careful exclusion of secondary causes of headache ^[9]. The same principle applies here: GCA is itself a dangerous secondary cause of headache and visual loss. Conversely, PMR is a diagnosis of exclusion — you must rule out malignancy, infection, and other inflammatory conditions that can mimic it.

A. Differential Diagnosis of GCA (Presenting as Headache ± Visual Loss ± Constitutional Symptoms in Elderly)

Think about what makes GCA distinctive: new-onset headache in a patient ≥ 50 years, temporal tenderness, jaw claudication, visual symptoms, markedly raised ESR, constitutional symptoms. Any condition that produces one or more of these features enters the differential.

Condition	Key Distinguishing Features	Why it mimics GCA
Takayasu arteritis	Age < 50 years (typically 10–40); predominantly affects females of reproductive age, especially in Asians ^[4]^[11]; "pulseless disease" with absent radial pulses, renal artery stenosis → HTN; bruits (80%), limb claudication (70%)	Both are granulomatous large vessel vasculitides with identical histology; GCA with large vessel involvement ("aortic arch syndrome") can mimic Takayasu's. DDx Takayasu's arteritis — both arm BP! ^[2]. The key separator is age: GCA ≥ 50, Takayasu < 50
Primary CNS vasculitis (PACNS)	Headache, cognitive decline, focal neurological deficits, seizures; CSF shows lymphocytic pleocytosis; angiography shows "beading" of intracranial vessels; ESR often normal	Affects intracranial vessels (unlike GCA which is primarily extracranial); no temporal artery abnormalities; diagnosed by brain/leptomeningeal biopsy

GCA vs Takayasu — The Age Rule

Both GCA and Takayasu are granulomatous inflammation of the aorta and its major branches ^[1]^[3]^[11]. In an exam, the single most reliable discriminator is age at onset: GCA ≥ 50, Takayasu < 50. In Hong Kong, Takayasu arteritis is more relevant than GCA because it is more common in Asians, while GCA is unusual in Asian populations ^[4]^[11].

These are critical because temporal arteritis must be considered in the DDx of any persistent unilateral/bilateral temporal headache in a patient > 50 years old ^[12]^[13].

Condition	Key Distinguishing Features	Why it mimics GCA
Primary headache disorders (migraine, tension-type, cluster)	Migraine: unilateral pulsating, 4–72 h, photo/phonophobia, nausea, debilitating; Tension-type: bilateral band-like, 30 min–7 days; Cluster: severe periorbital, 15–180 min, ipsilateral autonomic features ^[13]	Primary headaches can present de novo in the elderly, but new onset of headache in a patient > 60 should prompt consideration of temporal arteritis ^[13]. GCA headache is persistent (not episodic like cluster) and associated with scalp tenderness and raised ESR
Intracranial mass lesion	Progressive headache worse in morning, nausea/vomiting, focal neurological deficits, papilloedema; focal neurological symptoms, constitutional symptoms → mass lesion ^[13]	Constitutional symptoms (weight loss, fatigue) and new headache overlap, but mass lesions cause raised ICP signs and focal deficits rather than jaw claudication or temporal artery tenderness
Subarachnoid haemorrhage (SAH)	Thunderclap (worst) headache with dramatic onset, meningism after 6 hours, often during exertion ^[13]	Sudden severe headache, but SAH is hyperacute ("worst headache of life") while GCA headache builds over days–weeks; SAH lacks temporal artery signs and inflammatory markers
Cervical spondylosis (referred headache)	Commonly over occipital region, associated with neck stiffness and pain ^[13]	Occipital headache in elderly, but no temporal artery tenderness, no raised ESR, no jaw claudication
Cerebral venous sinus thrombosis (CVST)	Progressive headache, may be diffuse, papilloedema, seizures, focal deficits; diagnosed on CT/MR venography	Headache with raised ESR (from underlying prothrombotic state), but no temporal artery signs
Medication overuse headache	History of chronic analgesic use (> 15 days/month); daily or near-daily headache	Chronic headache in elderly taking multiple medications; no inflammatory markers elevation
Herpes zoster ophthalmicus	Dermatomal vesicular rash in V1 distribution; severe unilateral pain; may cause visual loss from keratitis/uveitis	Unilateral temporal pain in elderly with visual symptoms, but rash is pathognomonic

When GCA presents primarily with visual symptoms, the DDx centres on distinguishing arteritic from non-arteritic causes ^[7]:

Condition	Key Distinguishing Features	Why it mimics GCA
Non-arteritic AION (NAION)	Most common type of AION (94%); mean onset age 66 years (younger than AAION); associated with atherosclerosis risk factors (HT, DM), small optic cup, thrombophilia ^[7]; acute painless monocular loss of vision, typically clouding upon awakening (73%); fundoscopy shows pale, oedematous optic disc with peripapillary splinter haemorrhage but less pale than AAION (not "chalky white"); rarely associated with prodromal or systemic symptoms ^[7]	Both cause acute painless monocular visual loss with swollen disc. Key differences: AAION disc is very pale ("chalky white") vs NAION is less pale; AAION has systemic symptoms (headache, jaw claudication, PMR) and raised ESR/CRP while NAION usually does not; NAION as DDx → similar fundoscopy but usually less pale ^[4]
Central retinal artery occlusion (CRAO)	Sudden profound monocular visual loss (usually hand movements or worse); fundoscopy shows retinal whitening with cherry red spot, attenuated arteries ± Hollenhorst plaque; usually embolic (carotid atherosclerosis, cardiac); GCA can cause CRAO ^[7]^[8]	Both cause sudden monocular visual loss in elderly; check ESR/CRP in any elderly CRAO to exclude GCA as the underlying cause
Optic neuritis (demyelinating)	Usually in young females (18–45 years), painful eye movement, central scotoma, hyperaemic (not pale) disc ^[7]; associated with multiple sclerosis	Age and pain profile completely different from GCA; optic neuritis is painful, GCA visual loss is painless
Central retinal vein occlusion (CRVO)	Sudden painless monocular visual loss; fundoscopy shows "stormy sunset" — diffuse retinal haemorrhages, dilated tortuous veins, disc swelling, cotton wool spots; associated with HTN, DM, glaucoma	Disc swelling present in both, but CRVO has profuse haemorrhages and dilated veins (not pale disc)
Acute angle-closure glaucoma	Severe eye pain (not painless), red eye, mid-dilated fixed pupil, nausea/vomiting, raised IOP, corneal oedema	Painful (unlike GCA visual loss); acutely red eye with raised IOP on tonometry

AAION vs NAION — The Crucial DDx

In any patient > 50 years with acute painless monocular visual loss and a swollen optic disc, you MUST urgently check ESR/CRP to distinguish AAION (GCA) from NAION. If inflammatory markers are raised, treat as GCA empirically — do NOT wait for biopsy result ^[2]. Missing AAION means the other eye may go blind within days. The fundoscopic clue: AAION disc is chalky white, NAION disc is pale but not as white ^[4]^[7].

GCA can present as fever of unknown origin (FUO) with weight loss, elevated ESR, and anaemia — mimicking malignancy and chronic infections:

Condition	Key Distinguishing Features
Malignancy (lymphoma, solid tumours)	Weight loss, night sweats, fatigue, raised ESR; lymphadenopathy, hepatosplenomegaly, abnormal imaging; no temporal artery tenderness or jaw claudication
Infective endocarditis	Fever, new murmur, splinter haemorrhages, Janeway lesions, Osler nodes; positive blood cultures; can cause embolic visual loss (septic emboli)
Tuberculosis	Chronic fever, weight loss, night sweats; risk factors (Hong Kong: endemic area); CXR findings, positive sputum/culture
Other infections (abscess, osteomyelitis)	Localising signs, positive cultures

PMR is a diagnosis of exclusion — the cardinal features (bilateral shoulder/hip girdle pain, morning stiffness, raised ESR/CRP, age ≥ 50, rapid response to low-dose steroids) are non-specific and shared by many conditions. You must systematically exclude the following:

Key Differentials for PMR

Condition	Key Distinguishing Features	Why it mimics PMR
Late-onset rheumatoid arthritis (LORA)	Symmetrical small joint synovitis (MCP, PIP, wrists, MTP); RF/anti-CCP positive; prolonged morning stiffness (hours); erosive changes on X-ray ^[13]	LORA can present with proximal girdle involvement; but PMR lacks true synovitis of small peripheral joints and has negative autoantibodies ^[4]; morning stiffness in PMR is also prolonged but responds dramatically to low-dose steroids unlike RA
Polymyositis / Dermatomyositis	More overt proximal muscle weakness (not just pain) ^[14]; elevated CK (PMR has normal CK); EMG shows myopathic pattern; DM has characteristic skin findings (Gottron's papules, heliotrope eruption) ^[14]	Both cause proximal limb girdle symptoms; but myositis causes true weakness (can't rise from chair, can't lift arms) while PMR causes pain-limited movement (AROM reduced but PROM preserved). CK is the key differentiator — always check it
Hypothyroidism	Fatigue, weight gain, cold intolerance, constipation, bradycardia; proximal myopathy possible; elevated TSH, low free T4; CK may be mildly elevated	Proximal stiffness and myalgia with fatigue in elderly; but thyroid function tests distinguish
SLE	Symmetric polyarthritis (non-erosive, non-deforming); ANA/anti-dsDNA positive; malar rash, photosensitivity, serositis, cytopenias; morning stiffness usually in minutes (not as prolonged as RA) ^[14]	Polyarthralgia/myalgia with raised ESR, but SLE has multi-system involvement and positive autoantibodies
Malignancy (paraneoplastic PMR-like syndrome)	Atypical features: age < 50, asymmetric symptoms, poor response to steroids, lymphadenopathy, abnormal blood counts, unexplained weight loss disproportionate to other symptoms	Up to 5–10% of patients initially diagnosed with PMR are later found to have underlying malignancy; always screen with age-appropriate cancer investigations
Multiple myeloma	Bone pain (may be girdle distribution), anaemia, hypercalcaemia, renal impairment, raised ESR (often very high due to paraprotein); serum protein electrophoresis (SPEP) shows M-band	Very high ESR + bone pain + anaemia in elderly can perfectly mimic PMR; SPEP is essential to exclude
Fibromyalgia	Widespread pain, fatigue, poor sleep, tender points; ESR/CRP normal; no objective inflammatory signs	Chronic widespread pain in older adults; but PMR has objectively elevated inflammatory markers while fibromyalgia does not
Osteoarthritis (OA)	Mechanical pain (worse with activity, better with rest — opposite of PMR); no morning stiffness or brief (< 30 min); normal ESR/CRP; joint crepitus, Heberden/Bouchard nodes	Shoulder/hip pain in elderly, but OA is mechanical (not inflammatory) and ESR is normal
Crystal arthritis (CPPD — pseudogout)	CPPD can cause "crowned dens syndrome" with acute neck pain mimicking PMR; chondrocalcinosis on X-ray; aspirate shows positively birefringent rhomboid crystals	Acute proximal pain + raised inflammatory markers in elderly; imaging of C1–C2 region may show calcification
Bilateral adhesive capsulitis (frozen shoulder)	Insidious bilateral shoulder stiffness and pain; BOTH AROM and PROM reduced (unlike PMR where PROM preserved); normal inflammatory markers	Bilateral shoulder pain with restricted ROM; but in frozen shoulder, passive ROM is also limited, and ESR/CRP is normal
Infection (including endocarditis)	Fever, raised ESR/CRP, possibly proximal myalgia; blood cultures positive; splenomegaly, embolic phenomena	Constitutional symptoms with raised inflammatory markers; always consider endocarditis in unexplained elevated ESR with fever
Statin-induced myalgia	Recent statin initiation; proximal muscle pain/weakness; CK may be elevated; resolves on drug withdrawal	Very common in elderly patients on statins; drug history is key
Spondyloarthritis (axial SpA, enteropathic)	Inflammatory back pain (worse at rest, better with exercise); sacroiliitis on imaging; HLA-B27 positive; may have enthesitis, dactylitis	Proximal girdle stiffness; but SpA predominantly affects the axial skeleton and is typically younger onset

PMR Mimics — Red Flags for Alternative Diagnosis

Think twice about PMR if any of these are present:

Age < 50 — PMR is exceptionally rare; consider myopathy, SLE, SpA
True weakness (not just pain) — think inflammatory myopathy (PM/DM); check CK
Positive autoantibodies (RF, anti-CCP, ANA) — think RA, SLE, other CTD
Normal inflammatory markers — diagnosis is essentially excluded; think fibromyalgia, OA
Poor/no response to low-dose steroids within 3 days — reconsider; malignancy, myopathy, late-onset RA
Peripheral synovitis — suggests RA or other inflammatory arthritis, not isolated PMR
Very high ESR with bone pain — exclude myeloma (SPEP essential)

Presentation	GCA DDx	PMR DDx
Headache	Primary headaches (migraine, tension, cluster), SAH, intracranial mass, CVST, cervicogenic, medication overuse, herpes zoster ophthalmicus	—
Visual loss	NAION, CRAO (non-arteritic), optic neuritis, CRVO, acute glaucoma	—
Large vessel involvement	Takayasu arteritis (age < 50), atherosclerotic disease, fibromuscular dysplasia	—
Constitutional symptoms	Malignancy (lymphoma), endocarditis, TB, other infections, other vasculitides	Malignancy, infection, endocarditis
Proximal girdle pain/stiffness	—	Late-onset RA, PM/DM, hypothyroidism, malignancy/myeloma, fibromyalgia, OA, CPPD, adhesive capsulitis, statin myalgia, SpA, SLE
Very high ESR	GCA (both), myeloma, endocarditis, other vasculitis	PMR (both), myeloma, endocarditis, malignancy

Investigation	What it helps exclude	Rationale
ESR/CRP	Normal ESR/CRP virtually excludes GCA and PMR	Both conditions almost always have markedly elevated inflammatory markers
CK (creatine kinase)	If elevated → inflammatory myopathy (PM/DM), not PMR	PMR is periarticular inflammation, not myositis — CK is always normal
RF, anti-CCP	If positive → RA rather than PMR	PMR has negative autoantibodies ^[4]
ANA, anti-dsDNA	If positive → SLE or other CTD	SLE can mimic PMR but has multi-system features
TSH, free T4	Hypothyroidism	Reversible cause of proximal myopathy/stiffness
SPEP/UPEP	Multiple myeloma	Very high ESR + bone pain + anaemia in elderly
Blood cultures	Endocarditis	Fever + raised ESR + anaemia
Temporal artery biopsy/US	Confirms GCA (or excludes alternative dx at the artery)	Gold standard for GCA ^[3]; halo sign on US is supportive
Age-appropriate cancer screening	Occult malignancy	Paraneoplastic PMR-like syndrome

High Yield Summary — DDx of GCA and PMR

GCA DDx priorities:

NAION vs AAION is the critical visual loss DDx — urgent ESR/CRP differentiates; AAION disc is chalky white, NAION is less pale ^[4]^[7]
Takayasu arteritis is the key large vessel vasculitis DDx — separated by age (GCA ≥ 50, Takayasu < 50) ^[4]^[11]
New-onset headache in elderly must exclude GCA as a secondary cause ^[9]^[13]
Always consider endocarditis and malignancy in elderly with constitutional symptoms and very high ESR

PMR DDx priorities:

Late-onset RA — check RF/anti-CCP; RA has small joint synovitis
Inflammatory myopathy (PM/DM) — check CK; myopathy causes true weakness, PMR causes pain
Malignancy/myeloma — check SPEP; poor steroid response is a red flag
Hypothyroidism — check TSH; easily reversible
PMR has negative autoantibodies and normal CK — these are key exclusion tests
Dramatic response to low-dose steroids (10–15 mg/d) within days essentially confirms PMR ^[4]

Active Recall - DDx of GCA and PMR

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf, p87–88 ^[2] Senior notes: Maksim Medicine Notes.pdf, p311 ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p1158–1162 ^[4] Senior notes: Ryan Ho Rheumatology.pdf, p95–96 ^[7] Senior notes: Ryan Ho Opthalmology.pdf, p91–94 ^[8] Senior notes: Ryan Ho Opthalmology.pdf, p65 ^[9] Lecture slides: GC 082. Severe headache_headache and neuralgia; neuro-imaging I.pdf, p33 ^[11] Senior notes: Ryan Ho Rheumatology.pdf, p96 (Takayasu arteritis section) ^[12] Senior notes: Ryan Ho Fundamentals.pdf, p312 ^[13] Senior notes: Ryan Ho Fundamentals.pdf, p313, p408 ^[14] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf, p706, p712

Diagnostic Criteria for GCA

This is the classic, most widely examined set of criteria. The GC headache lecture explicitly presents these ^[9]:

Diagnostic criteria for temporal arteritis (TA) ^[9]:

Age at onset ≥ 50 years

New headaches

Abnormalities of temporal artery at clinical examination

Raised ESR (≥ 50 mm/hr)*

Abnormal findings on biopsy of temporal artery

N.B. 3 or more criteria: Dx of TA with 91.2% specificity & 93.5% sensitivity.

*Raised C-reactive protein ( > 5 mg/L) is another, currently used, clinically useful laboratory parameter ^[9]

Mnemonic: "BATHE" ^[2]

Letter	Criterion	Detail	Why this criterion?
B	Biopsy evidence	Abnormal arterial biopsy: evidence of vasculitis with mostly mononuclear cell infiltration or granulomatous inflammation or evidence of giant cells ^[3]^[9]	Histological proof of granulomatous arteritis is the gold standard; giant cells at the internal elastic lamina are pathognomonic
A	Age ≥ 50	GCA almost never occurs before 50	This epidemiological cut-off has near-perfect negative predictive value for excluding GCA in younger patients
T	Temporal artery abnormalities	Scalp tenderness, reduced pulsation ^[3]^[9]	Inflammation and thrombosis of the superficial temporal artery cause palpable thickening and loss of pulse
H	New onset localised Headache	Not pre-existing; typically temporal	Perivascular nociceptor stimulation by inflamed cranial arteries
E	ESR ≥ 50 mm/hr	ESR to confirm diagnosis (should be very high > 50 mm/hour) ^[3]	Reflects the massive IL-6–driven acute-phase response; ESR often exceeds 100 mm/hr

Important Nuances of ACR 1990 Criteria

These are classification criteria (designed to separate GCA from other vasculitides in research), not strictly diagnostic criteria. A patient can have GCA even if they do not meet 3/5 criteria — clinical judgement prevails.
Raised CRP ( > 5 mg/L) is another, currently used, clinically useful laboratory parameter ^[9] — the original 1990 criteria used ESR only, but in modern practice CRP is equally (or more) useful. Around 5% of biopsy-proven GCA patients have a normal ESR but elevated CRP.
The criteria do NOT include jaw claudication, visual symptoms, or PMR — yet these are among the most important clinical features. This is a known limitation.

The 2022 update addresses limitations of the 1990 criteria by incorporating imaging and using a weighted scoring system:

Step	Requirement
Mandatory entry criterion	Age ≥ 50 at onset + clinical diagnosis of vasculitis
Scoring (≥ 6 points classifies as GCA)	See below

Criterion	Points
Morning stiffness in shoulders/neck/hip girdle	+2
Sudden visual loss	+3
Jaw or tongue claudication	+2
New temporal headache	+2
Scalp tenderness	+2
Temporal artery abnormality on examination	+2
ESR ≥ 50 or CRP ≥ 10 mg/L	+3
Positive temporal artery biopsy	+5
Positive temporal artery halo sign on US	+5
Bilateral axillary artery involvement on imaging	+2
FDG-PET activity throughout the aorta	+2

Key advances: imaging (US halo sign, PET-CT, axillary involvement) now carries diagnostic weight, reflecting the GC tutorial learning objective that investigations for GCA, especially the role of imaging for GCA diagnosis are essential ^[5].

PMR does not have universally accepted formal diagnostic criteria in the same way GCA does. The 2012 ACR/EULAR Provisional Classification Criteria are used:

Mandatory entry criteria: Age ≥ 50, bilateral shoulder aching, abnormal CRP and/or ESR

Scoring algorithm (without ultrasound: ≥ 4 points; with ultrasound: ≥ 5 points):

Criterion	Points (without US)	Points (with US)
Morning stiffness > 45 min	2	2
Hip pain or limited ROM	1	1
Absence of RF and anti-CCP	2	2
Absence of other joint involvement	1	1
≥ 1 shoulder with subdeltoid bursitis and/or biceps tenosynovitis and/or glenohumeral synovitis AND ≥ 1 hip with synovitis and/or trochanteric bursitis	—	1
Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis	—	1

The key principle: PMR is essentially diagnosed by clinical presentation + raised inflammatory markers + negative autoantibodies ^[4] + dramatic response to low-dose steroids ^[4]. It remains a diagnosis of exclusion.

Diagnostic Algorithm

The diagnostic approach to GCA is driven by one overriding principle: GCA is a potentially sight-threatening disease and the importance of timely diagnosis and treatment ^[5] means you must never delay treatment to wait for investigation results when there is high clinical suspicion. For visual symptoms, do NOT wait for biopsy result → start empirical steroids ^[2].

Dx: based on clinical + ↑ESR + prompt response to steroid ^[4]. Tx started upon presumed clinical dx even despite –ve initial Ix ^[4].

Key Algorithm Principle — Treat First, Confirm Later

In GCA with visual symptoms, the algorithm is TREAT → INVESTIGATE → CONFIRM. This is the opposite of most conditions where you investigate first. Why? Because delay can put patient at risk for complications particularly sight loss ^[3]. The good news: resolution of inflammatory infiltrate in temporal artery occurs slowly after initiation of treatment so an accurate diagnosis of GCA can be made even several weeks or months after steroid treatment ^[3]. Steroids don't "wash away" the biopsy findings quickly.

Investigation Modalities — Detailed

A. Blood Investigations

Test	Expected Finding	Interpretation
ESR	Very high, often > 100 mm/hr ^[2]^[4]; diagnostic threshold ≥ 50 mm/hr ^[9]	Reflects the massive IL-6–driven hepatic acute-phase response (fibrinogen production ↑ → RBCs rouleaux faster → ESR rises). ESR to confirm diagnosis ^[3]. However, ~5% of biopsy-proven GCA can have normal ESR
CRP	Elevated, typically > 5–10 mg/L	CRP to monitor disease progression since it is more sensitive ^[3]. CRP reflects IL-6 activity more accurately and changes faster than ESR (ESR lags). A normal CRP + normal ESR together have very high NPV for excluding GCA

Why both? ESR can be falsely elevated by age, anaemia, polyclonal gammopathy, or infection. CRP is more specific to active inflammation. Using both together increases diagnostic accuracy. In the 2022 ACR/EULAR criteria, ESR ≥ 50 or CRP ≥ 10 mg/L earns 3 classification points.

Finding	Interpretation
Normochromic normocytic anaemia ^[3]^[4]^[6]	Anaemia of chronic disease/inflammation — IL-6 drives hepatic hepcidin production, which sequesters iron in macrophages, reducing iron availability for erythropoiesis. This is an unexplained anaemia ^[3]
Thrombocytosis (reactive) ^[3]^[4]^[6]	IL-6 stimulates hepatic thrombopoietin production → megakaryocyte proliferation → ↑platelets. Reactive (not clonal) — platelet count normalises with treatment
Leukocytosis ^[3]	Non-specific; reflects systemic inflammation

Finding	Interpretation
↑ALP (alkaline phosphatase) ^[6]	Found in ~30% of GCA; mechanism not fully understood but thought to relate to hepatic inflammation driven by IL-6; rarely due to hepatic granulomas. Often normalises with steroid treatment. Other LFTs usually normal

Test	Expected Finding	Why check?
RF, anti-CCP	Negative ^[4]	To exclude late-onset RA as a PMR mimic
ANA, anti-dsDNA	Negative	To exclude SLE and other CTD
ANCA	Negative	To exclude ANCA vasculitides (GPA, EGPA) which can also present with constitutional symptoms

Test	Purpose
CK	Must be normal in PMR; if elevated → myopathy (PM/DM)
TSH	Exclude hypothyroidism mimicking PMR
SPEP/UPEP	Exclude multiple myeloma (very high ESR + bone pain + anaemia)
Blood cultures	If febrile — exclude endocarditis
Renal function, glucose	Baseline before starting steroids (steroids cause hyperglycaemia, fluid retention)

B. Temporal Artery Biopsy

Temporal artery biopsy — GOLD standard in diagnosis of giant cell arteritis (GCA) ^[3]

This is the definitive diagnostic investigation. Let's understand every aspect:

Must order urgently ( < 24–48h) or else risk permanent visual impairment ^[6]
However: Do not delay steroid therapy while confirming diagnosis since delay can put patient at risk for complications particularly sight loss ^[3]
Resolution of inflammatory infiltrate in temporal artery occurs slowly after initiation of treatment so an accurate diagnosis of GCA can be made even several weeks or months after steroid treatment ^[3] — this is why you can start steroids AND still get a useful biopsy later. The histological changes persist for 2–6 weeks after steroid initiation.

Consult NS (neurosurgery) for biopsy ^[2]
1 side, 1 cm long ^[2] — ideally the clinically more affected side; current best practice recommends ≥ 1 cm (ideally 2 cm) of artery to reduce false negatives from skip lesions
Performed under local anaesthesia; the superficial temporal artery is palpated anterior to the tragus and a segment is excised

Feature	Description	Significance
Panarteritis	Inflammatory infiltrate involving all three layers (intima, media, adventitia) ^[4]	Defining feature — inflammation is transmural
Mixed inflammatory infiltrate	Mostly mononuclear cell infiltration: lymphocytes (CD4+ T cells), macrophages, plasma cells ^[3]^[9]	T-cell–mediated autoimmune process
Multinucleated giant cells	Evidence of giant cells ^[3]^[9] clustered at the internal elastic lamina	Classic but NOT required for diagnosis — absent in 20–50% of positive biopsies
Fragmentation of internal elastic lamina	Best seen on elastic van Gieson (EVG) stain	The elastic lamina is the primary target of the granulomatous attack; MMPs digest elastic fibres
Intimal hyperplasia	Concentric thickening of intima with myofibroblast proliferation	Causes luminal narrowing → ischaemia
Fibrinoid necrosis	Necrotizing arteritis ^[2] of the media	Severe active inflammation

Complications include FN result due to skip lesion, bleeding and facial nerve injury ^[3]
- Skip lesions: GCA inflammation is patchy (segmental) — a biopsy may sample an uninvolved segment. This is the main reason for false negatives (rate ~15–40%). May be falsely negative due to patchy inflammation ^[6]
- If initial biopsy is negative but clinical suspicion remains high → consider contralateral biopsy
- Bleeding: minor surgical risk
- Facial nerve injury: the temporal branch of CN VII runs close to the superficial temporal artery — careful surgical technique minimises this

Biopsy — Don't Let It Delay Treatment

The take-home message from multiple sources is clear: Temporal artery biopsy should be considered if ESR or CRP are abnormal with high clinical suspicion of GCA ^[3], but do NOT wait for biopsy result if visual symptoms are present — start empirical steroids ^[2]. The biopsy remains informative even after steroid initiation because histological changes persist for weeks.

C. Imaging Investigations

One of the key learning objectives from the GC interactive tutorial is investigations for GCA, especially the role of imaging for GCA diagnosis ^[5]. Imaging has become increasingly important and, in the 2022 ACR/EULAR criteria, now carries significant diagnostic weight.

Colour duplex US ^[1]^[4] is the first-line imaging modality in many centres:

Feature	Detail
Technique	High-frequency linear probe (≥ 15 MHz) placed over temporal, occipital, and facial arteries. Can also assess axillary arteries
Key finding	Halo sign ^[2]: a dark (hypoechoic) ring around the artery lumen, representing inflammatory oedema of the vessel wall. Pathognomonic when present
Sensitivity / Specificity	Halo sign: sensitivity ~77%, specificity ~96% for GCA (when performed by experienced operators)
Advantages	Non-invasive, no radiation, rapid, repeatable, can assess bilateral temporal + axillary arteries simultaneously
Limitations	Operator-dependent; halo sign disappears within days of starting steroids (unlike biopsy which persists for weeks); does not assess deep vessels (aorta)
Other US findings	Stenosis (narrowing with ↑ flow velocity), occlusion (absent flow signal), compression sign (halo remains visible when artery compressed)

Why "halo"? The inflammatory infiltrate and oedema in the vessel wall appear as a circumferential hypoechoic (dark) zone around the vessel lumen. It looks like a halo surrounding the bright flowing blood.

Feature	Detail
Technique	3T MRI with high-resolution, contrast-enhanced T1-weighted sequences centred on temporal arteries
Key finding	Mural thickening and contrast enhancement of the temporal artery wall
Advantages	Can detect inflammation beyond the biopsy site; not operator-dependent like US
Limitations	Expensive, limited availability, less validated than US and biopsy

Aortography if indicated — uncommon ^[1], but important for assessing large vessel involvement:

Feature	Detail
Indications	Suspected large vessel GCA (limb claudication, asymmetric BP, bruits); screening for aortic aneurysm/dissection ^[2]; aortic arch syndrome
Key findings	Wall thickening and enhancement of aorta and branches; stenosis/occlusion/ectasia of subclavian, axillary, carotid, vertebral arteries; aortic aneurysm (especially thoracic ascending aorta)
When?	At diagnosis if large vessel symptoms present; consider baseline imaging in all GCA patients to screen for subclinical aortitis; long-term surveillance for aortic aneurysm

Feature	Detail
Principle	FDG is taken up by metabolically active inflammatory cells (macrophages, T cells) in the vessel wall → "lights up" on PET
Key finding	Increased FDG uptake in the walls of the aorta and its branches — the hallmark of large vessel vasculitis. Can show cranial AND extracranial involvement
Advantages	Whole-body assessment in a single scan; can detect subclinical large vessel involvement that is clinically silent; useful when biopsy and US are inconclusive
Limitations	Expensive; low spatial resolution (cannot reliably assess temporal arteries); FDG uptake decreases rapidly after starting steroids (ideally performed before or within 3 days of steroid initiation); aortic atherosclerosis can cause false-positive uptake
Role in 2022 criteria	FDG-PET activity throughout the aorta earns classification points

Imaging in GCA — When to Use What

First-line: Colour duplex US of temporal ± axillary arteries — rapid, non-invasive, high specificity (halo sign). Best done BEFORE steroids (halo disappears within days of treatment).
Gold standard: Temporal artery biopsy — remains the definitive test; can be done even after steroids have been started (histology persists for weeks).
Large vessel assessment: CTA/MRA of aorta — if clinical suspicion of aortic arch syndrome or for baseline screening.
Comprehensive assessment: FDG-PET/CT — best for detecting subclinical large vessel involvement; ideally performed before steroids.

In any GCA patient with visual complaints (or even without — screening is prudent):

Assessment	Findings in GCA
Visual acuity	↓VA ^[7] — may range from mild reduction to no light perception
Pupil examination	RAPD+ (relative afferent pupillary defect) ^[7] — the affected eye's afferent pathway is damaged
Visual fields	Altitudinal VF defect ^[7] — typically superior or inferior hemianopia
Colour vision	↓colour vision ^[7]
Fundoscopy	Very pale ("chalky white"), swollen optic disc with peripapillary haemorrhages ^[4]^[7] in AAION; ± C/BRAO, cotton wool spots at posterior pole ^[7]
Fluorescein angiography	Delayed or absent choroidal filling; optic disc hypoperfusion

PMR investigations are primarily aimed at excluding mimics rather than confirming the diagnosis:

Investigation	Expected Finding	Purpose
ESR/CRP	Almost always elevated ^[4]	Supports diagnosis; used for monitoring
CBC	NcNc anaemia ^[4]	Anaemia of inflammation
CK	Normal	Excludes inflammatory myopathy
RF, anti-CCP	Negative ^[4]	Excludes RA
TSH	Normal	Excludes hypothyroidism
SPEP	No M-band	Excludes myeloma
ALP	May be mildly elevated	Non-specific
Shoulder/hip US	Subdeltoid/subacromial bursitis, biceps tenosynovitis, glenohumeral or hip joint synovitis, trochanteric bursitis	Supports diagnosis; part of 2012 ACR/EULAR criteria
Steroid response	Dramatic improvement within 1–3 days of 10–15 mg/d prednisolone ^[4]	Effectively a therapeutic trial that confirms diagnosis

Investigation	GCA	PMR	Key Finding
ESR	≥ 50, often > 100	Elevated	Acute-phase response
CRP	Elevated ( > 5 mg/L)	Elevated	More sensitive than ESR for monitoring
CBC	NcNc anaemia, thrombocytosis, leukocytosis	NcNc anaemia	IL-6–driven changes
LFT	↑ALP	May be mildly ↑ALP	Hepatic IL-6 effect
Autoantibodies	Negative	Negative	Exclude RA, SLE, ANCA vasculitis
CK	Normal	Normal	Exclude myopathy
Temporal artery US	Halo sign	Not applicable	First-line imaging for GCA
Temporal artery biopsy	Gold standard: granulomatous arteritis ± giant cells	Not applicable	Definitive but may be falsely –ve
CTA/MRA aorta	Wall thickening, stenosis, aneurysm	Not applicable	Large vessel assessment
FDG-PET/CT	FDG uptake in aorta/branches	May show bursitis/synovitis (research)	Whole-body vasculitis assessment
Shoulder/hip US	May show bursitis if co-existing PMR	Bursitis/tenosynovitis	Supports PMR diagnosis
Fundoscopy	Chalky white swollen disc	Normal	AAION assessment

High Yield Summary — Diagnosis of GCA and PMR

GCA Diagnostic Criteria (ACR 1990 — "BATHE"):

≥ 3 of 5: Biopsy + Age ≥ 50 + Temporal artery tenderness + new Headache + ESR ≥ 50 ^[2]^[9]
91.2% specificity, 93.5% sensitivity ^[9]
CRP > 5 mg/L is another currently used, clinically useful laboratory parameter ^[9]

Key Investigations:

Temporal artery biopsy = gold standard ^[3] — but do NOT delay steroids for biopsy if visual symptoms ^[2]
Colour duplex US ^[1] — halo sign (hypoechoic ring around artery) — first-line imaging, highly specific
ESR often > 100 ^[2], plus NcNc anaemia, thrombocytosis, ↑ALP ^[6]
Biopsy can still diagnose GCA even weeks-months after starting steroids ^[3]
FN biopsy can occur due to skip lesions ^[3]^[6] — consider contralateral biopsy

PMR Diagnosis:

Clinical: age ≥ 50, bilateral shoulder/hip girdle pain/stiffness, morning stiffness > 45 min
Labs: ↑ESR/CRP, negative autoantibodies, normal CK
Dramatic response to low-dose prednisolone (10-15 mg/d) confirms diagnosis ^[4]
Always screen for concurrent GCA symptoms

Algorithm Principle: In GCA with visual symptoms → TREAT → INVESTIGATE → CONFIRM (not the other way around)

Active Recall - Diagnosis of GCA and PMR

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf, p87–88 ^[2] Senior notes: Maksim Medicine Notes.pdf, p311 ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p1158–1162 ^[4] Senior notes: Ryan Ho Rheumatology.pdf, p95–96 ^[5] Lecture slides: GC_Interactive tutorial (Rheum case 1) student copy.pdf, p1 ^[6] Senior notes: Ryan Ho Neurology.pdf, p65 ^[7] Senior notes: Ryan Ho Opthalmology.pdf, p91–94 ^[9] Lecture slides: GC 082. Severe headache_headache and neuralgia; neuro-imaging I.pdf, p33–34

Management of GCA and PMR

Before diving into specifics, let's establish the foundational management principles — these dictate every treatment decision:

GCA is a potentially sight-threatening disease and the importance of timely diagnosis and treatment ^[5] — treatment must be initiated immediately upon clinical suspicion, especially if visual symptoms are present.
For visual S/S, do NOT wait for biopsy result → start empirical steroids ^[2]. Significant visual recovery is unlikely but treatment is aimed at preventing vision loss in the OTHER eye ^[3].
GCA and PMR often co-exist… However, treatment of these conditions is not the same. PMR patients require lower doses of steroid ^[1]. Why? Because PMR does not threaten the eyes — there is no ischaemic optic neuropathy risk, so lower-dose steroids suffice to control periarticular inflammation.
Tx started upon presumed clinical dx even despite –ve initial Ix ^[4] — a negative biopsy does NOT exclude GCA if clinical suspicion remains high.
Usually a/w dramatic response to steroid (complete resolution of S/S ≤ 48–72h of Tx) ^[4] — this rapid response itself supports the diagnosis and can be used as a therapeutic-diagnostic tool.

Treatment Modalities — Detailed

A. Corticosteroids — The Cornerstone of Treatment

Corticosteroids are the mainstay of therapy for both GCA and PMR. Understanding the pharmacology helps you understand dose choices.

Why do steroids work? Glucocorticoids bind intracellular glucocorticoid receptors → translocate to the nucleus → suppress transcription of pro-inflammatory cytokines (IL-1, IL-6, TNF-α, IFN-γ) → suppress T-cell activation, macrophage function, and giant cell formation → shut down the granulomatous inflammatory cascade. They also reduce vascular permeability and oedema → rapid symptom relief.

Scenario	Regimen	Rationale
Non-sight-threatening GCA (headache, jaw claudication, constitutional Sx, no visual symptoms)	Oral prednisolone 1 mg/kg/day (typically 40–60 mg/day) ^[1]^[2]^[3]^[4]	High enough to suppress the active granulomatous vasculitis and prevent progression to ischaemic complications
Sight-threatening GCA (amaurosis fugax, visual loss, diplopia, AAION)	IV methylprednisolone 500 mg–1 g daily for 3 days ^[3]^[6], then switch to oral prednisolone 1 mg/kg/day	IV pulsed steroids achieve rapid, high-concentration drug delivery to suppress active arterial inflammation and prevent contralateral eye involvement. Parenteral high dose if complications already occurred ^[6]

High-dose prednisolone 1 mg/kg/day: save vision of other eye & prevent brainstem stroke ^[2]

EARLY high dose oral/IV corticosteroids. High dose = 1 mg/kg/day. Oral = Prednisolone; IV = Methylprednisolone ^[3]

Expected response:

Usually a/w dramatic response to steroid (complete resolution of S/S ≤ 48–72h of Tx) ^[4]
Headache and constitutional symptoms typically resolve within 24–72 hours
ESR/CRP begin to normalise within 1–2 weeks
However, significant visual recovery is unlikely ^[3] — once AAION causes optic nerve infarction, the damage is usually permanent. The goal is to prevent vision loss in the OTHER eye ^[3]

Steroid taper protocol for GCA:

Phase	Dose Adjustment	Duration
Initial	Prednisolone 40–60 mg/day (or post-IV pulse)	2–4 weeks (until symptoms resolve and ESR/CRP normalise)
Early taper	Reduce by 10 mg every 2 weeks	Until reaching 20 mg/day
Mid taper	Reduce by 2.5 mg every 2–4 weeks	Until reaching 10 mg/day
Late taper	Reduce by 1 mg every 1–2 months	Until discontinuation or minimum maintenance dose
Total duration	—	Slowly tapered over 1–2 years ^[4]

Gradual ↓dosage to maintenance level according to ESR level ^[6] — each dose reduction should be guided by symptoms AND inflammatory markers. If symptoms recur or ESR/CRP rise → increase back to the last effective dose.

Regimen	Detail
Low dose corticosteroid: 10–15 mg/d prednisolone PO sufficient ^[4]	This is a critical exam point — PMR requires MUCH less steroid than GCA
Why lower?	PMR involves periarticular inflammation (bursitis/tenosynovitis) without the arterial wall granulomatous process that threatens the eyes. Lower doses adequately suppress the less severe inflammatory process
Response	Dramatic improvement within 1–3 days; failure to respond should prompt reconsideration of the diagnosis

PMR taper protocol:

Phase	Dose Adjustment
Initial	10–15 mg/day for 2–4 weeks
Taper	Reduce by 1–2.5 mg every 2–4 weeks, guided by symptoms and ESR/CRP
Maintenance	Many patients require 5–7.5 mg/day for months
Duration	Usually self-limiting → ~50% can discontinue steroid after 1–2 years ^[4]

GCA vs PMR Steroid Dosing — The Exam Trap

Treatment of these conditions is not the same. PMR patients require lower doses of steroid ^[1]. This is a common exam question: GCA = high-dose (1 mg/kg/day ≈ 40–60 mg), PMR = low-dose (10–15 mg). If you give a PMR patient high-dose steroids, they'll improve (because it's the same disease spectrum), but you'll cause unnecessary steroid side effects. If you give a GCA patient only low-dose steroids, you risk blindness.

Long-term steroid use in elderly patients (often 1–2+ years) causes significant morbidity. You must co-prescribe protective agents:

Side Effect	Mechanism	Prevention
Osteoporosis → fractures	Steroids inhibit osteoblast function, promote osteoclast activity, reduce intestinal calcium absorption, increase renal calcium excretion	Calcium and vitamin D supplements or bisphosphonates should be considered for prevention of osteoporosis ^[3]. Alendronate 70 mg weekly or risedronate. DEXA scan at baseline
Peptic ulcer / GI bleeding	Steroids reduce prostaglandin-mediated gastroprotection; risk compounded by co-prescribed aspirin	Gastroprotective agents such as PPIs should be administered in view of the concomitant use of glucocorticoids and aspirin ^[3]
Hyperglycaemia / steroid-induced diabetes	Steroids promote hepatic gluconeogenesis, reduce peripheral glucose uptake, cause insulin resistance	Monitor blood glucose regularly; may need oral hypoglycaemics or insulin
Hypertension	Mineralocorticoid effect: sodium/water retention	Monitor BP; adjust antihypertensives
Immunosuppression → infections	Suppression of cell-mediated and humoral immunity	PJP prophylaxis if prednisolone ≥ 20 mg for ≥ 4 weeks (co-trimoxazole); consider VZV risk
Adrenal suppression	Exogenous steroids suppress HPA axis via negative feedback → adrenal atrophy	Never stop steroids abruptly; always taper; patient needs steroid sick-day rules and medic alert
Cataracts, glaucoma	Posterior subcapsular cataracts from altered lens protein metabolism; raised IOP from reduced aqueous outflow	Regular ophthalmology review
Cushing's syndrome features	Moon face, buffalo hump, central obesity, skin thinning, easy bruising, striae, proximal myopathy	Clinical monitoring; aim to minimise dose and duration
Psychiatric	Insomnia, mood disturbance, psychosis (rare at standard GCA doses)	Counsel patient; consider taking dose in the morning

Steroid Co-prescribing Checklist

For any patient starting medium-to-high dose steroids for GCA/PMR, co-prescribe:

Calcium + Vitamin D (e.g., calcium carbonate 500 mg + cholecalciferol 1000 IU daily)
Bisphosphonate (e.g., alendronate 70 mg weekly) — especially if DEXA T-score ≤ −1.5 or age > 70
PPI (e.g., omeprazole 20 mg daily) — especially if also on aspirin/NSAID
Glucose monitoring — capillary blood glucose regularly
Steroid card / medic alert

Addition of low-dose aspirin reduces risk of visual loss, transient ischemic attacks or stroke ^[3]

Feature	Detail
Dose	75–100 mg daily
Mechanism	Irreversibly inhibits COX-1 → reduces thromboxane A2 → inhibits platelet aggregation → reduces thrombotic risk in inflamed, prothrombotic arteries
Rationale	GCA causes endothelial damage and intimal proliferation → the arterial lumen becomes prothrombotic. Aspirin reduces the risk of superimposed thrombosis causing complete occlusion → reduces ischaemic complications (visual loss, stroke, TIA)
Co-prescribe with	PPI (gastroprotective agent) in view of the concomitant use of glucocorticoids and aspirin ^[3] — both steroids and aspirin independently increase GI ulcer risk; together, the risk is multiplicative
Contraindications	Active GI bleeding, aspirin allergy, severe thrombocytopaenia
Evidence	Observational studies suggest ~50% reduction in cranial ischaemic events with aspirin; although RCT evidence is limited, it is recommended by BSR/BHPR and EULAR guidelines

C. Steroid-Sparing Agents

Why are steroid-sparing agents needed? Because many GCA patients relapse during steroid taper (40–60% experience at least one relapse) and long-term steroid use in elderly patients causes cumulative toxicity. The GC lecture and senior notes specifically mention two key steroid-sparing agents:

Anti-IL6 ^[1] — "toci" = tocilizumab, "lizumab" = humanised monoclonal antibody

Feature	Detail
Mechanism	Humanised monoclonal antibody against the IL-6 receptor (IL-6R). IL-6 is THE dominant pro-inflammatory cytokine in GCA driving both the granulomatous vasculitis and the systemic acute-phase response. Blocking IL-6R → suppresses T-cell activation, macrophage recruitment, hepatic acute-phase protein production (CRP, fibrinogen), and constitutional symptoms
Indication	Steroid-sparing agent: tocilizumab (anti-IL6)… upon relapsing disease ^[4]. Now recommended by 2023 BSR/BHPR and 2023 EULAR guidelines as first-line steroid-sparing agent in all newly diagnosed GCA (not just relapsing disease) — this is a significant guideline update from the senior notes era
Evidence	GiACTA trial (NEJM 2017): tocilizumab 162 mg SC weekly or biweekly + 26-week prednisone taper achieved sustained remission in ~56% vs ~14% with prednisone alone, with dramatically reduced cumulative steroid exposure
Dose	162 mg SC weekly (or every 2 weeks); some centres use IV tocilizumab 8 mg/kg monthly
Duration	Typically ≥ 1 year; some patients require longer-term therapy
Key caution	Tocilizumab suppresses CRP production (because CRP is IL-6–dependent) → CRP becomes unreliable as a monitoring marker. Must rely on clinical symptoms and ESR (which is less affected) for monitoring disease activity
Side effects	Hepatotoxicity (↑ALT), neutropaenia, ↑LDL cholesterol, infections (including GI perforation risk — avoid in diverticular disease), injection site reactions
Contraindications	Active infection, diverticulitis, severe hepatic impairment, neutropaenia (ANC < 0.5 × 10⁹/L)

Tocilizumab — 2023 Guideline Update

The GC lecture lists anti-IL6 as a treatment for GCA ^[1]. Since the GiACTA trial, tocilizumab has moved from "relapsing disease" to recommended first-line adjunct in new GCA (2023 BSR/EULAR guidelines). The rationale: it allows faster steroid taper and reduces cumulative steroid toxicity — particularly important in elderly patients prone to osteoporosis, diabetes, and infections. In exams, mention tocilizumab as a steroid-sparing agent and cite its mechanism (anti-IL-6 receptor).

Methotrexate ^[1]

Feature	Detail
Mechanism	Folate antagonist; at low doses, acts primarily as an immunomodulator (inhibits AICAR transformylase → adenosine accumulation → anti-inflammatory effects; also suppresses T-cell proliferation). "Metho-trex-ate" → interferes with folate metabolism
Indication	Methotrexate upon relapsing disease ^[4]; used when tocilizumab is unavailable, contraindicated, or as a second-line steroid-sparing agent
Evidence	Meta-analyses of 3 small RCTs suggest modest benefit in reducing relapse rates and cumulative steroid dose, but evidence is weaker than for tocilizumab
Dose	7.5–25 mg PO/SC once weekly + folic acid 5 mg weekly (taken on a different day to MTX)
Side effects	Hepatotoxicity, bone marrow suppression (pancytopaenia), pneumonitis, oral ulcers, teratogenicity
Contraindications	Significant renal impairment (MTX is renally cleared), pre-existing liver disease, active infection, pregnancy/breastfeeding, bone marrow failure
Monitoring	FBC, LFT, renal function every 2–4 weeks initially, then every 2–3 months

Agent	Role	Comment
Azathioprine	Steroid-sparing in refractory cases	Purine synthesis inhibitor; less evidence than MTX or tocilizumab for GCA; more commonly used in Takayasu
Leflunomide	Alternative steroid-sparing agent	Pyrimidine synthesis inhibitor; limited evidence in GCA
Ustekinumab (anti-IL-12/23)	Under investigation	Targets Th1/Th17 pathways; early trial data mixed
Abatacept (CTLA-4-Ig)	Under investigation for relapsing GCA	Blocks T-cell co-stimulation; some efficacy in pilot studies
Secukinumab (anti-IL-17A)	Under investigation	Targets the Th17 pathway; early phase trials
JAK inhibitors (baricitinib, upadacitinib)	Emerging	Inhibit JAK-STAT signalling downstream of multiple cytokines including IL-6; active clinical trials

E. Management of Specific Complications

Step	Action	Rationale
Immediate	IV methylprednisolone 500 mg–1 g daily for 3 days ^[3]	Rapid high-dose steroid to suppress active vasculitis and save vision of other eye & prevent brainstem stroke ^[2]
Then	Oral prednisolone 1 mg/kg/day with slow taper	Maintain suppression
Ophthalmology	Urgent ophtho review, visual acuity, fields, fundoscopy	Document severity and monitor for contralateral involvement
Prognosis	Significant visual recovery is unlikely ^[3] — vision already lost in the affected eye is usually permanent	Treatment prevents FURTHER loss, not reversal

Aortic arch syndrome: aneurysm, dissection, stenosis of aorta and its major branches ^[2]
Manage with high-dose steroids + steroid-sparing agents
Both arm BP! ^[2] — monitor for asymmetry indicating subclavian/axillary stenosis
Baseline CTA/MRA aorta at diagnosis; periodic imaging surveillance (annual CXR or CT) for aortic aneurysm
Thoracic aortic aneurysm ≥ 5.5 cm → vascular surgery referral for consideration of repair
Aortic dissection → emergency management (as per standard dissection protocol)

Standard acute stroke management if stroke occurs
Low-dose aspirin for secondary prevention
Steroid dose escalation if vasculitis is the suspected cause

Parameter	Frequency	Purpose
Symptoms (headache, jaw claudication, visual Sx, PMR stiffness)	Every visit	Detect relapse; guide steroid taper
ESR and CRP	Every 2–4 weeks during taper; monthly once stable	CRP to monitor disease progression since it is more sensitive ^[3]; gradual ↓dosage to maintenance level according to ESR level ^[6]. Note: CRP unreliable if on tocilizumab
CBC	Every 2–4 weeks initially	Monitor for steroid-induced leukocytosis; detect anaemia improvement; MTX bone marrow suppression
Blood glucose	Regularly	Steroid-induced hyperglycaemia
Blood pressure	Every visit	Steroid-induced HTN
LFT	If on MTX or tocilizumab	Hepatotoxicity monitoring
Bone density (DEXA)	Baseline, then every 1–2 years	Steroid-induced osteoporosis
Ophthalmology review	Baseline and if any visual symptoms	Monitor for cataract, glaucoma, visual complications
Aortic imaging	Baseline CTA/MRA; periodic surveillance	Aortic aneurysm screening — thoracic aortic aneurysm risk is ~10–20% in GCA patients

Aspect	GCA	PMR
First-line	High-dose prednisolone 1 mg/kg/day ^[1]^[2]^[3]^[4] (40–60 mg/d)	Low-dose prednisolone 10–15 mg/d ^[4]
If sight-threatening	IV methylprednisolone 500 mg–1 g × 3 days ^[3] then oral	N/A
Steroid-sparing	Tocilizumab (anti-IL6) ^[1]^[4] first-line; methotrexate ^[1]^[4] second-line	Methotrexate (for steroid-dependent cases)
Adjuncts	Low-dose aspirin ^[3] + PPI; Ca²⁺ + Vit D; bisphosphonate	Ca²⁺ + Vit D; bisphosphonate; PPI if needed
Taper duration	1–2 years, slowly tapered ^[4]	1–2 years; ~50% can discontinue ^[4]
Monitoring	ESR/CRP, symptoms, aortic imaging	ESR/CRP, symptoms, GCA screening
Prognosis	Dramatic response to steroid (≤ 48–72h) ^[4]	Dramatic response within 1–3 days

High Yield Summary — Management of GCA and PMR

GCA Management:

Urgent high-dose prednisolone 1–2 mg/kg/day — start on clinical suspicion, do NOT wait for biopsy ^[2]
IV methylprednisolone if sight-threatening (AAION, amaurosis fugax) ^[3]
Treatment aims to prevent vision loss in the OTHER eye — recovery of lost vision is unlikely ^[3]
Steroid-sparing agents: tocilizumab (anti-IL-6) and methotrexate ^[1]^[4]
Low-dose aspirin reduces risk of visual loss, TIA, and stroke — co-prescribe PPI ^[3]
Calcium, vitamin D, and bisphosphonates for osteoporosis prevention ^[3]
Slowly taper steroids over 1–2 years guided by ESR/CRP and symptoms ^[4]^[6]
Screen for aortic aneurysm with baseline imaging

PMR Management:

Low-dose prednisolone 10–15 mg/day sufficient ^[4] — NOT the same dose as GCA ^[1]
Dramatic response within days confirms diagnosis
Self-limiting: ~50% can discontinue steroids after 1–2 years ^[4]
Always screen for concurrent GCA throughout treatment

Co-prescribing checklist: Ca²⁺ + Vit D, bisphosphonate, PPI (if on aspirin), glucose monitoring, BP monitoring, steroid card

Active Recall - Management of GCA and PMR

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf, p87–88 ^[2] Senior notes: Maksim Medicine Notes.pdf, p311 ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf, p1160–1162 ^[4] Senior notes: Ryan Ho Rheumatology.pdf, p95–96 ^[5] Lecture slides: GC_Interactive tutorial (Rheum case 1) student copy.pdf, p1 ^[6] Senior notes: Ryan Ho Neurology.pdf, p65

Complications of GCA and PMR

Complications can be divided into two major categories:

Disease-related complications — direct consequences of the vasculitis or the inflammatory process itself
Treatment-related complications — consequences of long-term corticosteroid therapy (and other immunosuppressants)

Both categories are critical because GCA/PMR patients are typically elderly (age ≥ 70), meaning they are already vulnerable to osteoporosis, infections, diabetes, and cardiovascular disease — steroids amplify every one of these risks.

Permanent visual loss — MOST feared complication of GCA ^[3]

This is the complication that makes GCA a medical emergency. Let's break down the mechanisms:

Mechanism	Frequency	Pathophysiology
Anterior ischaemic optic neuropathy (AION) (80%)	Most common cause	Occlusion of posterior ciliary artery which is a branch of ophthalmic artery from ICA and is the main arterial supply to the optic nerve ^[3]. Granulomatous vasculitis → intimal hyperplasia + thrombosis → complete occlusion of posterior ciliary arteries → infarction of the optic nerve head. Fundoscopy: chalky white, swollen optic disc with peripapillary haemorrhages ^[4]^[7]
Central retinal artery occlusion (CRAO) (10%)	Second most common	Vasculitis-induced thrombosis of the central retinal artery → inner retinal infarction. Fundoscopy: diffuse retinal whitening + cherry red spot + attenuated arteries ^[7]^[8]
Posterior ischaemic optic neuropathy (PION) ( < 5%)	Rare	Interruption of blood flow to retrobulbar portion of optic nerve ^[3] — the optic nerve behind the globe is affected rather than the disc. Fundoscopy may be initially normal (no disc swelling), making it harder to diagnose acutely; optic atrophy develops later
Branch retinal artery occlusion (BRAO)	Uncommon	Vasculitis of a branch retinal artery → sectoral retinal infarction → partial visual field loss
Cerebral ischaemia (occipital lobe infarction)	Rare	Lesion in vertebrobasilar circulation leading to occipital lobe infarction ^[3] → cortical blindness (bilateral) or homonymous hemianopia (unilateral)

Key clinical points:

May be preceded by amaurosis fugax ^[2]^[4] — transient monocular visual loss is a warning sign of impending permanent blindness. It represents transient ischaemia before complete thrombotic occlusion occurs. If a patient with GCA reports amaurosis fugax, treat it as an emergency.
15–20% permanent visual loss ^[2]^[4] if untreated
Significant visual recovery is unlikely but treatment is aimed at preventing vision loss in the OTHER eye ^[3] — once the optic nerve is infarcted, the damage is almost always irreversible. Bilateral blindness can occur within days if untreated.
Permanent visual loss (8%), ophthalmological complications mostly optic neuropathy, ~20% ^[9]

Visual Loss in GCA — Irreversible and Bilateral

Do not reassure patients or yourselves that "it's only one eye." Without urgent treatment, the contralateral eye is at very high risk — bilateral sequential AAION can occur within hours to days. This is why high-dose prednisolone 1 mg/kg/day saves vision of the other eye & prevents brainstem stroke ^[2]. Amaurosis fugax is the warning shot — act on it.

Other ocular manifestations of GCA:

Giant cell arteritis: AAION, CRAO ^[8] — these are the two principal ocular complications
Double vision, diplopia (2%) ^[9]: ischaemia of CN III, IV, or VI (supplied by branches of the ophthalmic and posterior cerebral arteries) or extraocular muscles themselves → cranial nerve palsies → diplopia
Scintillating scotoma (5%) ^[9]: may result from retinal or cortical ischaemia, mimicking migraine aura

Aortic arch syndrome: aneurysm, dissection, stenosis of aorta and its major branches (DDx Takayasu's arteritis) — both arm BP! ^[2]

GCA is fundamentally an aortitis, and large vessel involvement causes some of the most serious long-term complications:

Complication	Pathophysiology	Clinical Presentation	Significance
Thoracic aortic aneurysm	MMPs and ROS from giant cells destroy the elastic media of the aorta → weakening of the aortic wall → progressive dilatation	Often asymptomatic until large; may present with chest/back pain, hoarseness (recurrent laryngeal nerve stretch), dysphagia (oesophageal compression). Risk of rupture if > 5.5 cm	GCA patients have a 17× increased risk of thoracic aortic aneurysm and 2.4× risk of abdominal aortic aneurysm compared to age-matched controls. May develop years after the initial GCA diagnosis, even after the vasculitis is "treated"
Aortic dissection	Medial necrosis from vasculitis weakens the aortic wall → intimal tear → blood enters the media, creating a false lumen	Acute severe tearing chest/back pain radiating to the back; asymmetric BP/pulses; may cause aortic regurgitation, cardiac tamponade, stroke, mesenteric/renal ischaemia	Life-threatening emergency; higher mortality than atherosclerotic dissection due to fragile inflamed tissue
Large artery stenosis/occlusion	Intimal hyperplasia in subclavian, axillary, carotid, vertebral arteries → luminal narrowing	Limb claudication (8%) ^[9] (especially upper limb); asymmetric BP; absent/weak pulses; bruits	Can mimic atherosclerotic peripheral vascular disease; both arm BP measurement is essential ^[2]
Aortic regurgitation	Aortic root dilatation from aneurysm → stretching of the aortic valve annulus → failure of leaflet coaptation	Early diastolic murmur at left sternal edge; wide pulse pressure; eventually heart failure	Uncommon but important to auscultate for

Why does aortic disease develop late? The initial granulomatous inflammation weakens the structural integrity of the aortic wall (MMP-mediated elastic fibre destruction). Even after steroids suppress active inflammation, the structural damage is permanent. The weakened wall continues to dilate under haemodynamic stress over years → aneurysm formation is a late, insidious complication. This is why long-term aortic surveillance (annual CXR or periodic CTA/MRA) is recommended for all GCA patients.

TIA/Stroke (7%) ^[9]
Mechanism: GCA preferentially affects extracranial arteries (vertebral, carotid) because they have internal elastic lamina and vasa vasorum. Thrombosis due to vessel wall thickening → basilar artery → posterior circulation infarct ^[6]. Posterior circulation strokes (vertebrobasilar territory) are more common than anterior circulation strokes in GCA.
Urgent Tx prevents blindness and brainstem stroke ^[6]
Clinical features of posterior circulation stroke: vertigo, ataxia, dysarthria, dysphagia, visual field defects, crossed neurological signs

Complication	Frequency	Pathophysiology
Neuropathy (14%) ^[9]	Relatively common	Ischaemia of vasa nervorum (the small arteries feeding peripheral nerves) → mononeuropathy or mononeuritis multiplex. Can affect cranial nerves (especially CN III, VI) or peripheral nerves
Neuro-otological disorder (7%) ^[9]	Uncommon	Ischaemia of the labyrinthine artery (branch of AICA/basilar) → sensorineural hearing loss, vertigo, tinnitus
Myelopathy (0.6%) ^[9]	Very rare	Ischaemia of the anterior spinal artery (branch of vertebral arteries) → spinal cord infarction → paraplegia, bladder/bowel dysfunction

Complication	Detail
Tongue claudication (4%) ^[9]	Ischaemia of the tongue via lingual artery (branch of ECA) involvement; can rarely progress to tongue necrosis/gangrene in severe untreated cases
Scalp necrosis	Severe ischaemia of the superficial temporal and occipital arteries → scalp infarction. Rare but dramatic — patches of necrotic scalp tissue
Jaw/masseter necrosis	Extreme extension of the jaw claudication process → actual muscle infarction if arterial supply is completely occluded. Very rare
Sore throat, dysphagia (11%) ^[9]	Pharyngeal/laryngeal artery ischaemia → mucosal ischaemia
Cough (17%) ^[9]	Pharyngeal/laryngeal ischaemia or centrally mediated cough reflex sensitisation
Depression (3%) ^[9]	Multifactorial: chronic illness, pain, steroid side effects, cytokine effects on CNS, social isolation

PMR itself does not typically cause end-organ damage (no ischaemic optic neuropathy, no aortic aneurysm from PMR alone). The main disease-related complications of PMR are:

Complication	Detail
Progression to GCA	~10–15% of PMR patients will develop GCA during their disease course. Must continuously screen for GCA symptoms (headache, jaw claudication, visual symptoms) throughout treatment
Functional disability	Severe girdle pain and stiffness → difficulty with activities of daily living (dressing, bathing, reaching overhead). Shoulder abduction < 90° limits independence
Frozen shoulder (adhesive capsulitis)	Prolonged immobility from pain can lead to secondary capsular contracture

These are arguably more morbid than the disease itself in many patients, because GCA/PMR require prolonged steroid use (1–2+ years) in an elderly population already predisposed to every steroid complication. Understanding these is essential both for exams and clinical practice.

Complication	Mechanism	Clinical Significance	Prevention/Monitoring
Osteoporosis → fragility fractures	Steroids inhibit osteoblast function (↓bone formation), promote osteoclast activity (↑bone resorption), reduce intestinal calcium absorption, increase renal calcium wasting	Vertebral compression fractures, hip fractures → significant morbidity and mortality in elderly. Calcium, vitamin D supplements or bisphosphonates should be considered for prevention of osteoporosis ^[3]	DEXA at baseline; calcium + vitamin D supplementation; bisphosphonate (alendronate, risedronate); consider denosumab if bisphosphonate contraindicated
Steroid-induced diabetes / hyperglycaemia	Steroids promote hepatic gluconeogenesis, reduce peripheral glucose uptake, and cause insulin resistance	New-onset diabetes or worsening of pre-existing diabetes; fasting and postprandial hyperglycaemia	Regular blood glucose monitoring; HbA1c at baseline and periodically; may need oral hypoglycaemics or insulin
Infections	Immunosuppression → impaired cell-mediated and humoral immunity	Increased susceptibility to bacterial, viral (VZV reactivation/shingles), fungal (oral/oesophageal candidiasis), and opportunistic infections (PJP if prednisolone ≥ 20 mg for ≥ 4 weeks)	PJP prophylaxis (co-trimoxazole); VZV vaccination if not contraindicated; influenza/pneumococcal vaccination; low threshold for investigating febrile episodes
Peptic ulcer disease / GI bleeding	Steroids reduce prostaglandin-mediated gastric mucosal protection; risk compounded by aspirin co-administration	Epigastric pain, haematemesis, melaena; GI perforation	Gastroprotective agents such as PPIs should be administered in view of the concomitant use of glucocorticoids and aspirin ^[3]
Adrenal suppression	Exogenous steroids suppress the HPA axis via negative feedback → adrenal cortical atrophy → inability to mount an endogenous cortisol response	Risk of adrenal crisis if steroids stopped abruptly or during physiological stress (illness, surgery, trauma): hypotension, hypoglycaemia, collapse	Never stop steroids abruptly — always taper; steroid sick-day rules (double dose during illness); steroid emergency card/medic alert bracelet
Cataracts	Posterior subcapsular cataracts from altered lens protein metabolism (glucocorticoids cause cross-linking of lens crystallins)	Progressive painless visual blurring; may compound visual problems already caused by GCA	Regular ophthalmology review; surgical extraction when visually significant
Glaucoma	Steroids reduce aqueous humour outflow via trabecular meshwork changes → raised IOP	Asymptomatic initially; can cause optic nerve damage if prolonged	Monitor IOP; especially important in GCA patients already at risk of optic nerve damage
Cardiovascular disease	Steroids promote HTN (mineralocorticoid effect), dyslipidaemia, insulin resistance, central obesity → accelerated atherosclerosis	Increased risk of MI, stroke, heart failure; compounded by the elderly demographic	Monitor BP; manage cardiovascular risk factors aggressively
Cushing syndrome features	Supra-physiological cortisol → redistribution of fat (central), protein catabolism (skin thinning, striae, easy bruising), proximal myopathy	Moon face, buffalo hump, truncal obesity, thin skin with bruising, abdominal striae, proximal muscle weakness	Aim for minimum effective steroid dose; use steroid-sparing agents (tocilizumab, methotrexate) to facilitate faster taper
Proximal myopathy	Steroid-induced muscle protein catabolism → type II fibre atrophy	Difficulty rising from a chair, climbing stairs — may be confused with PMR relapse. Key difference: steroid myopathy causes weakness (CK normal), while PMR causes pain and stiffness	Clinical distinction; physiotherapy; dose reduction
Psychiatric effects	Steroids affect CNS neurotransmitter systems (serotonin, GABA)	Insomnia, euphoria, irritability, depression, psychosis (rare at GCA doses)	Take steroids in the morning; counsel patients and families; psychiatric referral if severe
Skin thinning and poor wound healing	Steroids inhibit collagen synthesis and fibroblast activity	Easy bruising (senile purpura + steroid purpura), poor wound healing, skin tears	Gentle handling; protect skin from trauma
Avascular necrosis (AVN) of bone	Steroids cause fat cell hypertrophy within bone → ↑intraosseous pressure → compromised blood supply (especially femoral head)	Hip/knee pain (especially with weight-bearing); may require joint replacement	MRI if symptomatic; maintain lowest effective dose

Steroid Myopathy vs PMR Relapse — A Clinical Trap

Both present with proximal limb girdle symptoms. Steroid myopathy causes true weakness (difficulty rising from chair due to weak quadriceps, not pain) with normal ESR/CRP and normal CK. PMR relapse causes pain and stiffness with rising ESR/CRP. The management is opposite: for steroid myopathy you reduce the steroid dose; for PMR relapse you increase it. Getting this wrong worsens the patient's condition either way.

Agent	Key Complications
Tocilizumab	Hepatotoxicity (↑ALT), neutropaenia, ↑LDL cholesterol, infections (especially GI infections), GI perforation (caution in diverticular disease), injection site reactions
Methotrexate	Hepatotoxicity, bone marrow suppression (pancytopaenia), MTX pneumonitis (acute onset dyspnoea, cough, fever), oral ulcers, teratogenicity, infections

Category	Complications
Ophthalmological	AAION (80%), CRAO (10%), PION ( < 5%), BRAO, cortical blindness, diplopia (CN palsies), amaurosis fugax (warning sign)
Aortic / large vessel	Thoracic/abdominal aortic aneurysm, aortic dissection, large artery stenosis/occlusion, aortic regurgitation
Cerebrovascular	Posterior circulation stroke, TIA (7%)
Neurological	Peripheral neuropathy (14%), neuro-otological (7%), myelopathy (0.6%)
Other ischaemic	Tongue/scalp/jaw necrosis, pharyngeal ischaemia
PMR-specific	Progression to GCA (10–15%), functional disability, secondary frozen shoulder
Steroid complications	Osteoporosis/fractures, steroid diabetes, infections, peptic ulcer, adrenal suppression, cataracts, glaucoma, CVD, Cushing syndrome, AVN, psychiatric effects

High Yield Summary — Complications of GCA and PMR

Disease complications of GCA:

Permanent visual loss is the MOST feared complication — caused by AAION (80%), CRAO (10%), PION ( < 5%), or occipital cortical infarction ^[3]
15–20% permanent visual loss if untreated; may be preceded by amaurosis fugax (warning sign) ^[2]^[4]
Treatment aims to prevent vision loss in the OTHER eye — recovery of lost vision is unlikely ^[3]
Aortic arch syndrome: aneurysm, dissection, stenosis — 17× increased risk of thoracic aortic aneurysm; requires long-term surveillance ^[2]
TIA/Stroke (7%) — typically posterior circulation via vertebral artery involvement ^[9]
Neuropathy (14%), neuro-otological (7%), myelopathy (0.6%) ^[9]

Disease complications of PMR:

Risk of progression to GCA (10–15%) — must screen continuously
Functional disability from girdle stiffness

Treatment complications (steroids):

Osteoporosis/fractures — prevent with calcium, vitamin D, bisphosphonates ^[3]
GI ulcer/bleeding — prevent with PPI, especially if co-prescribed aspirin ^[3]
Steroid diabetes, infections, adrenal suppression, cataracts, glaucoma, Cushing syndrome, AVN, proximal myopathy
Steroid myopathy vs PMR relapse: myopathy = weakness with normal ESR; relapse = pain with rising ESR

Active Recall - Complications of GCA and PMR

References

High Yield Summary

GCA:

Granulomatous arteritis of aorta and its major branches; commonest form of primary vasculitis ^[1]^[2]
Almost never < 50 years; F:M = 2:1; less common in Asians
Pathophysiology: Adventitial dendritic cells activate → T cell and macrophage recruitment → granuloma formation → MMP/ROS → elastic lamina destruction → intimal hyperplasia → luminal narrowing → ischaemia
Key symptoms: New temporal headache (72%), jaw claudication (40%, pathognomonic), amaurosis fugax/visual loss, PMR (58%), constitutional symptoms
Key signs: Tender, non-pulsatile temporal artery; scalp tenderness; chalky white swollen disc (AAION); asymmetric BP
ACR criteria (BATHE): Biopsy + Age ≥ 50 + Temporal artery tenderness + Headache + ESR > 50 (≥ 3/5)
EMERGENCY: Do NOT wait for biopsy if visual symptoms — start empirical steroids immediately
GCA and PMR often co-exist but treatment is NOT the same — PMR requires lower doses of steroid

PMR:

Sudden onset bilateral shoulder/hip girdle pain and severe morning stiffness
↓AROM with preserved PROM; shoulder abduction < 90°
Elevated ESR/CRP with negative autoantibodies
Responds to low-dose prednisolone (10–15 mg/day); usually self-limiting (50% stop steroids after 1–2 years)

High Yield Summary — DDx of GCA and PMR

GCA DDx priorities:

NAION vs AAION is the critical visual loss DDx — urgent ESR/CRP differentiates; AAION disc is chalky white, NAION is less pale ^[4]^[7]
Takayasu arteritis is the key large vessel vasculitis DDx — separated by age (GCA ≥ 50, Takayasu < 50) ^[4]^[11]
New-onset headache in elderly must exclude GCA as a secondary cause ^[9]^[13]
Always consider endocarditis and malignancy in elderly with constitutional symptoms and very high ESR

PMR DDx priorities:

Late-onset RA — check RF/anti-CCP; RA has small joint synovitis
Inflammatory myopathy (PM/DM) — check CK; myopathy causes true weakness, PMR causes pain
Malignancy/myeloma — check SPEP; poor steroid response is a red flag
Hypothyroidism — check TSH; easily reversible
PMR has negative autoantibodies and normal CK — these are key exclusion tests
Dramatic response to low-dose steroids (10–15 mg/d) within days essentially confirms PMR ^[4]

High Yield Summary — Diagnosis of GCA and PMR

GCA Diagnostic Criteria (ACR 1990 — "BATHE"):

≥ 3 of 5: Biopsy + Age ≥ 50 + Temporal artery tenderness + new Headache + ESR ≥ 50 ^[2]^[9]
91.2% specificity, 93.5% sensitivity ^[9]
CRP > 5 mg/L is another currently used, clinically useful laboratory parameter ^[9]

Key Investigations:

Temporal artery biopsy = gold standard ^[3] — but do NOT delay steroids for biopsy if visual symptoms ^[2]
Colour duplex US ^[1] — halo sign (hypoechoic ring around artery) — first-line imaging, highly specific
ESR often > 100 ^[2], plus NcNc anaemia, thrombocytosis, ↑ALP ^[6]
Biopsy can still diagnose GCA even weeks-months after starting steroids ^[3]
FN biopsy can occur due to skip lesions ^[3]^[6] — consider contralateral biopsy

PMR Diagnosis:

Clinical: age ≥ 50, bilateral shoulder/hip girdle pain/stiffness, morning stiffness > 45 min
Labs: ↑ESR/CRP, negative autoantibodies, normal CK
Dramatic response to low-dose prednisolone (10-15 mg/d) confirms diagnosis ^[4]
Always screen for concurrent GCA symptoms

Algorithm Principle: In GCA with visual symptoms → TREAT → INVESTIGATE → CONFIRM (not the other way around)

High Yield Summary — Management of GCA and PMR

GCA Management:

Urgent high-dose prednisolone 1–2 mg/kg/day — start on clinical suspicion, do NOT wait for biopsy ^[2]
IV methylprednisolone if sight-threatening (AAION, amaurosis fugax) ^[3]
Treatment aims to prevent vision loss in the OTHER eye — recovery of lost vision is unlikely ^[3]
Steroid-sparing agents: tocilizumab (anti-IL-6) and methotrexate ^[1]^[4]
Low-dose aspirin reduces risk of visual loss, TIA, and stroke — co-prescribe PPI ^[3]
Calcium, vitamin D, and bisphosphonates for osteoporosis prevention ^[3]
Slowly taper steroids over 1–2 years guided by ESR/CRP and symptoms ^[4]^[6]
Screen for aortic aneurysm with baseline imaging

PMR Management:

Low-dose prednisolone 10–15 mg/day sufficient ^[4] — NOT the same dose as GCA ^[1]
Dramatic response within days confirms diagnosis
Self-limiting: ~50% can discontinue steroids after 1–2 years ^[4]
Always screen for concurrent GCA throughout treatment

Co-prescribing checklist: Ca²⁺ + Vit D, bisphosphonate, PPI (if on aspirin), glucose monitoring, BP monitoring, steroid card

High Yield Summary — Complications of GCA and PMR

Disease complications of GCA:

Permanent visual loss is the MOST feared complication — caused by AAION (80%), CRAO (10%), PION ( < 5%), or occipital cortical infarction ^[3]
15–20% permanent visual loss if untreated; may be preceded by amaurosis fugax (warning sign) ^[2]^[4]
Treatment aims to prevent vision loss in the OTHER eye — recovery of lost vision is unlikely ^[3]
Aortic arch syndrome: aneurysm, dissection, stenosis — 17× increased risk of thoracic aortic aneurysm; requires long-term surveillance ^[2]
TIA/Stroke (7%) — typically posterior circulation via vertebral artery involvement ^[9]
Neuropathy (14%), neuro-otological (7%), myelopathy (0.6%) ^[9]

Disease complications of PMR:

Risk of progression to GCA (10–15%) — must screen continuously
Functional disability from girdle stiffness

Treatment complications (steroids):

Osteoporosis/fractures — prevent with calcium, vitamin D, bisphosphonates ^[3]
GI ulcer/bleeding — prevent with PPI, especially if co-prescribed aspirin ^[3]
Steroid diabetes, infections, adrenal suppression, cataracts, glaucoma, Cushing syndrome, AVN, proximal myopathy
Steroid myopathy vs PMR relapse: myopathy = weakness with normal ESR; relapse = pain with rising ESR

Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica

References

Definition

Epidemiology

GCA Epidemiology

PMR Epidemiology

Risk Factors

Anatomy and Function

Arterial Targets in GCA

Why These Arteries?

Key Anatomical Points for Clinical Correlation

PMR: Anatomical Basis

Etiology and Pathophysiology

Etiology

Pathophysiology of GCA — Step by Step

Key Pathological Steps Explained

Histopathology

Pathophysiology of PMR

Classification

Chapel Hill Classification (2012 Revised)

ACR 1990 Classification Criteria for GCA (≥ 3 of 5)

2022 ACR/EULAR Classification Criteria for GCA

GCA Subtypes (Clinical Classification)

Clinical Features

Overview of Presentation Frequencies

Symptoms (with Pathophysiological Basis)

1. Headache (72%)

2. Jaw Claudication (40%)

3. Tongue Claudication (4%)

4. Visual Symptoms

5. Polymyalgia Rheumatica Symptoms (58%)

6. Constitutional Symptoms

7. Respiratory Symptoms

8. Neurological Symptoms

9. Limb Claudication (8%)

Signs (with Pathophysiological Basis)

1. Temporal Artery Abnormalities

2. Scalp Tenderness

3. Vascular Signs

4. Fundoscopic Signs (in AAION)

5. PMR Signs

Summary of GCA vs PMR Clinical Features

Active Recall - GCA and PMR

References

Differential Diagnosis of GCA and PMR

A. Differential Diagnosis of GCA (Presenting as Headache ± Visual Loss ± Constitutional Symptoms in Elderly)

Approach: Why Each Condition Mimics GCA

1. Other Large Vessel Vasculitides

2. Other Causes of New-Onset Headache in Elderly

3. Other Causes of Acute Visual Loss (DDx for AAION)

4. Systemic Conditions Mimicking GCA Constitutional Symptoms

B. Differential Diagnosis of PMR (Presenting as Bilateral Proximal Girdle Pain and Stiffness)

Key Differentials for PMR

C. DDx Summary Table — Comprehensive

D. Key Distinguishing Investigations in the DDx

Active Recall - DDx of GCA and PMR

References

Diagnostic Criteria for GCA

ACR 1990 Classification Criteria for GCA

2022 ACR/EULAR Classification Criteria for GCA (Updated)

Diagnostic/Classification Criteria for PMR

Diagnostic Algorithm

Overall Approach

GCA Diagnostic Algorithm

PMR Diagnostic Algorithm

Investigation Modalities — Detailed

A. Blood Investigations

1. Inflammatory Markers: ESR and CRP

2. Complete Blood Count (CBC)

3. Liver Function Tests (LFT)

4. Autoantibodies

5. Other Baseline Bloods

B. Temporal Artery Biopsy

Timing

Technique

Histopathological Findings

Limitations

C. Imaging Investigations

1. Colour Duplex Ultrasound of Temporal Arteries

2. Temporal Artery MRI (High-Resolution)