Giant cell arteritis + Polymyalgia rheumatica Flashcards
(21 cards)
What is the key complication of GCA?
irreversible blindness
Risk factors for GCA
Occurs in age >50 (never <50), typically age 7-80
Females > males
More common in Northern European/Scandinavians descent
What is the most common form of systemic vasculitis in adults?
GCA
Briefly describe pathophysiology of GCA
How does GCA cause vision loss?
If one eye is affected, what is the risk to the other eye if left untreated?
• Genetic predisposition + environmental. Certain HLA alleles important. Possible environmental precipitant such as infection with Mycoplasma, Chlamydia pneumoniae, parvovirus B19, VZV
• Granulomatous vasculitis of large- and medium-sized vessels
• Most commonly affects the extra-cranial branches of the external carotid artery
• Inflammation occurs in the vessel wall which causes proliferation and thickening of the intima, vessel narrowing, and subsequent ischemia. This can result in end-organ damage:
○ Vessels supplying optic nerve (typically ophthalmic artery) -> anterior ischemic optic neuropathy (AION) -> permanent blindness or amaurosis fugax. Can also cause blindness by central retinal artery occlusion. If one eye is affected, 20-50% chance of losing vision in other eye if not treated.
Cortical vessels -> stroke or TIA
Describe clinical presentation of GCA
• New onset headache aged >50 years
• Jaw claudication
○ Rarely, dental pain, tongue claudication/tongue infarction
○ Good predictor of +ve temporal artery biopsy (along with diplopia)
• Temporal artery abnormalities: swollen artery, tenderness, nodularity, decreased/absent pulse
○ Other extra-cranial arteries can be involved: scalp tenderness (eg, occipital artery, post-auricular artery involvement), facial artery involvement
• Visual changes:
○ Diplopia -> if present, good predictor of +ve temporal artery biopsy (along with jaw claudication)
○ Decreased vision, permanent blindness (due to AION). Will see optic disc oedema & pallor +/- haemorrhage & cotton wool spots. If one eye is affected, 20-50% chance of losing vision in other eye if not treated.
○ Amaurosis fugax
• Associated polymyalgia rheumatica - 50% of patients with GCA will have PMR
• Constitutional symptoms: fevers, chills, malaise, anorexia, weight loss
• Neurological symptoms:
○ TIA or stroke
• If large vessel involvement (stenosis & aneurysm):
○ Aortitis, most commonly ascending aorta (hence, can consider TTE to monitor for large vessel aneurysm rather than angiography).
§ Can cause aortic artery aneurysms which can be lethal if ruptures or dissects.
§ Can cause aortic regurgitation
○ Subclavian, axillary, brachial artery: upper limb claudication. Results in pain with use of upper limbs, asymmetric blood pressure, decreased/absent pulses, subclavian/axillary bruit on examination
○ Carotid bruit
Rarely, lower limb claudication
What do you expect with ESR, CRP, FBE, LFTs, auto-antibodies to be in GCA?
- ESR: >50 is part of diagnostic criteria. Typically >100, if above this value has good positive predictive value of +ve temporal artery biopsy
- CRP may be elevated; normocytic normochromic anemia (anemia of chronic disease); mild leukocytosis; mild thrombocytosis; mild transaminase & ALP derangement
- Auto-antibodies typically -ve (eg, RF, ANA)
What is the gold standard of diagnosis of GCA?
Which side? What if it’s negative? How big of a sample and why?
What are you looking for on the biopsy?
What is the yield of the biopsy if primarily large vessel presentation?
○ Temporal artery biopsy - Gold standard in diagnosis. Take biopsy from side of symptoms. If negative, take biopsy from contralateral side.
○ Need adequate sample of 3-5cm as there can be patchy/segmental involvement leading to false -ve results.
○ Looking for granulomatous inflammation. Multinucleated giant cells present in ~50% of cases but not required for diagnosis.
However, yield of temporal artery biopsy is low (~50% sensitivity) if patient has primarily large vessel presentation (eg, aorta, subclavian, etc).
Role of angiography in GCA?
• Conventional angiography, CTA, MRA
To diagnose and monitor large vessel involvement (aneurysms)
How do you differentiate GCA from Takayasu arteritis?
How do you differentiate GCA from non-arteritic anterior ischemic optic neuropathy?
• Non-arteritic anterior ischaemic optic neuropathy (NAION) - can mimic the visual loss in GCA, however will not have the other large vessel and systemic features
Takayasu arteritis: main difference is TA occurs in younger patients (20s to 30s), typically female, and preferentially attacks the large vessels rather than the extra-cranial vessels
American College Rheumatology diagnostic criteria for GCA
Diagnostic criteria (American College of Rheumatology) - need 3/5 of the following:
• Age >50
• ESR >50
• New onset headache
• Temporal artery abnormality: tenderness, decreased/absent pulse, nodulatory, swollen
• +ve temporal artery biopsy
Should you delay steroids in GCA until biopsy or blood results?
How long can the biopsy stay +ve for despite steroids?
Do not delay steroids while awaiting results of blood tests, or while awaiting temporal artery biopsy. The temporal artery biopsy can remain +ve even after weeks-months of steroids
Describe the typical disease course of GCA
Typically disease course runs over 2-3 years, with significant rates of unpredictable relapse requiring increase in steroids.
Describe the management of GCA
• Corticosteroids
○ If no neurologic or visual symptoms -> PO prednisolone 1mg/kg for 4 weeks, then gradually taper by 10% every 2 weeks over 6-12 months.
○ If neurologic symptoms or visual changes -> IV methylprednisolone pulse 1g/day for 3 days, then PO prednisolone. This initial pulse allows overall lower corticosteroid total dose.
• Tocilizumab (anti-IL6 receptor antibody) if relapsing/refractory disease or significant glucocorticoid toxicity. Corticosteroid sparing effect as it allows for significantly shorter duration of glucocorticoid therapy without increased risk of adverse events + higher rates of remission + fewer relapses.
○ Can also consider methotrexate for steroid sparing effect, but less preferred. Only if major glucocorticoid toxicity.
• Aspirin 100mg/day: may reduce preventing ischemic complications (vision loss, stroke/TIA)
• Monitoring for large vessel involvement and aneurysms:
○ Angiography on initial diagnosis
○ Then angiography every 2-5 years
○ If aneurysm identified, need angiography every 6-12 months
○ Can consider TTE as monitoring as most common site of aneurysm is ascending aorta, however this will not visualise remainder of large arteries.
What is PMR?
PMR is an inflammatory rheumatological disorder that manifests as pain and morning stiffness in the shoulder and pelvic girdles
Risk factors for PMR
Age >50
Females > males
Northern European descent
What is the relationship between GCA and PMR?
Bidirectional relationship with GCA. 20% of PMR have GCA; 50% of GCA have PMR
What is the clinical presentation of PMR?
• Typically female, >50 years, Northern European descent
• Pain + morning stiffness (>1hr) of neck, shoulder, hip girdles (shoulder > hip). Improves throughout the day with activity. Getting out of bed difficult in the morning or rising from chair.
• Can have associated muscle tenderness.
• Constitutional symptoms: low grade fever, malaise, anorexia, night sweats, weight loss, anorexia.
• Other possible features:
○ Peripheral oligoarthritis: presenting as asymmetric joint pain
○ Bursitis: subacromial and trochanteric bursitis
○ Tenosynovitis: swelling of hands and feet
Rapid response to low dose steroids within 24-72hrs very helpful in supporting diagnosis of PMR.
Pertinent negatives in the history/exam of PMR?
Pertinent negatives: absence of oral ulcers, rash, cardiopulmonary abnormalities, focal neurologic findings, features of GCA.
Important DDx for PMR?
- Hypothyroidism: can occasionally present with arthralgias and stiffness
- Myeloproliferative disorders: presents as constitutional symptoms, bony pain, etc. Hence may overlap with PMR.
- Myositis: if hip pain predominates, myositis should be considered as DDx
- Fibromyalgia: pain tends to be more widespread and not associated with shoulder/hip girdle stiffness. Does not typically respond to prednisolone.
- Late onset RA: presentation similar to PMR but lack of response to low-dose corticosteroids distinguishes it from PMR.
- GCA
RS3PE syndrome
What investigations are important in PMR?
• ESR and CRP: elevated in most cases and supports diagnosis. However, normal values does not rule out diagnosis as rarely PMR can present with normal markers of systemic inflammation.
• TFTs, CK, FBE/blood film/SPEP, RF/anti-CCP to exclude DDx above.
• Ultrasound & MRI to distinguish bursitis, synovitis, and tenosynovitis
○ Symmetric bilateral shoulder/hip bursitis or tenosynovitis, in the absence of synovitis, would be more suggestive of PMR. In contrast, symmetric bilateral shoulder or hip arthritis in the absence of bursitis or tenosynovitis would be more suggestive of systemic arthritis eg, RA.
IL-6: elevated IL6 characteristic of PMR. Sensitive and supports diagnosis, but not specific enough to be used as diagnostic test.
What is the treatment for PMR?
• Corticosteroids
○ Mainstay of treatment is low dose corticosteroids. Response is usually rapid within 24-72hrs. Continue lowest effective dose (~12.5-25mg/day prednisolone) until complete symptom resolution + normalisation of ESR/CRP. Then taper to ~10mg/day over 4-8 weeks. Then slow taper ~1mg/month.
○ If relapse, increase dose to pre-relapse dose and slowly taper again.
○ Usually slow tapering over 2-3 years is often required to prevent relapses and exacerbations.
• Methotrexate ○ Used as steroid sparing agent in patients with relapsed disease, refractory disease, prolonged therapy, or corticosteroids associated with significant adverse effects. • Tocilizumab: used in case reports in treatment-resistant cases. Has been approved for use in GCA, but not for isolated PMR.
Avoid concomitant NSAID to reduce risk of GI bleeding.
