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Flashcards in Vasculitis Deck (81)
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Lower limb purpura without haematuria is often _______   ______ due to frusemide, antibiotics, allopurinol



Lower limb purpura without haematuria is often leucocytoclastic vasculitis due to frusemide, antibiotics, allopurinol

  • characteristic appearance
  • even if patient on longterm frusemide, if change in dose, at risk
  • no need to biopsy
  • dependent, can be in the arms too
  • check for haematuria
  • cease the medication




Patients with WG or MPA at presentation have high _____ directed against ____ or ____. Low levels in other diseases 


Patients with WG or MPA at presentation have high ANCA directed against PR3 or MPO. Low levels in other diseases 




Patients with vasculitis improve within days of starting ______ and _______



Patients with vasculitis improve within days of starting cyclophosphamide and steroids 

creatinine & urinary red cell cast will start to stabilise within 48 hours, then resolve within 1 week




Monitor patients treated with cyclophosphamide lifelong for ______ due to ______  _______



Monitor patients treated with cyclophosphamide lifelong for haematuria due to bladder cancer 




___-ANCA are associated with more frequent relapses 



PR3-ANCA are associated with more frequent relapses 


In what other conditions than vasculitis, is ANCA present?



ANCA also occur in interstitial lung disease, bronchiectasis, cystic fibrosis 




Any medications that produce ______ _________ can also produce ANCA but often without ________ ________



Any medications that produce a lupus anticoagulant can also produce ANCA but often without thrombotic tendency 




_______  drugs induce ANCA and vasculitis 



Antithyroid drugs induce ANCA and vasculitis 


Describe hypersensitivity vasculitis

palpable purpura in dependent areas e.g. feet, ankles, fingers

  • aka ‘cutaneous’ or ‘leucocytoclastic’ vasculitis 
  • ARA criteria –3/5
    • Age > 16 years
    • Temporal relationship with drug
    • Palpable purpura
    • Maculopapular rash
    • Perivascular neutrophils on skin biopsy
  • Commonly due to sulphonamides (lasix, thiazide), penicillins, cephalosporins, allopurinol, phenytoin. Even if longterm medication, dose change can also cause it.  
  • No renal involvement. May have minor visceral involvement 
  • Usually no specific treatment required -just stop the drug


Describe microscopic polyangiitis (MPA)


  • Palpable purpura plus systemic features
  • Glomerular haematuria, renal impairment, abnormal liver function 
  • P-ANCA with MPO-specificity 


Which ANCA with what specificity does microscopic polyangiitis have?

P-ANCA with MPO-specificity 


Clinical features suggesting vasculitis


  • Palpable purpura
    • Isolated -hypersensitivity vasculitis
    • With systemic features -microscopic polyangiitis
  • Multi-organ disease plus systemic features 
  • Pulmonary-renal disease (haemoptysis plus haematuria) –half are Wegener’s granulomatosis or microscopic polyangiitis 
  • Mononeuritis multiplex –only other common cause is diabetes


DDx of vasculitis


  • Thrombocytopenia
  • Infective endocarditis 
  • Septicemia
  • Amyloidosis 
  • Cholesterol emboli
  • Atrial myxoma with emboli
  • Mycotic aneurysm with emboli 


Ix in suspected vasculitis


  • FBE, CRP, ESR 
  • APTT and PT
  • Urinalysis and serum creatinine
  • Liver function tests 
  • ANA, ANCA, Rh F, cryoglobulins, AECA, lupus anticoagulant, anticardiolipin antibodies 
  • C3 and C4 
  • Hepatitis B, C, sometimes EBV, CMV
  • Chest X ray, arteriography (PAN, Takayasu, GCA), ultrasound (GCA), CT, MRI and PET 
  • Tissue, skin, artery, renal biopsy +/- IF for IgA etc 


New nomenclature for small vessel vasculitis


  • Granulomatous polyangiitis (GPA); previously Wegener granulomatosis
  • Eosinophilic granulomatous polyangiitis (EGPA); previously Churg-Strauss syndrome 
  • Microscopic polyangiitis (MPA)


New ANCA consensus statement on testing: 

Test for ___ and ___-ANCA directly if small vessel vasculitis is suspected at presentation 



Test for PR3-and MPO-ANCA directly if small vessel vasculitis is suspected at presentation 


These guidelines have no recommendations for using ANCA to monitor patients with vasculitis nor for the diagnosis of other diseases eg ILD, IBD, PSC etc. most often helpful to get immunoflorescence 


Classification of vasculitis & relevant conditions

1. large vessel vasculitis

  • takayasu arteritis
  • giant cell arteritis

2. medium vessel vasculitis

  • polyarteritis nodosa
  • kawasaki disease

3. Small vessel vasculitis

  • ANCA-assoicated small vessel vasculitis
    • microscopic polyangiitis
    • granulomatosis with polyangiitis (Wegener's)
    • eosinophilic granulomatosis with polyangiitis (Churg-Strauss)  
  • immune complex small vessel
    • cryoglobulinaemic vasculitis
    • IgA vasculitis (Henoch-Schonlein)
    • hypocomplementemic urticarial vasculitis (anti-C1q vascuitis)
    • anti-GBM disease 

4. Variable vessel vasculitis

  • Behcet’s disease 
  • Cogan disease 

5. Single organ vasculitis 

  • Leucocytoclastic vasculitis 
  • CNS vasculitis 

6. Vasculitis associated with probable aetiology

  • Hep C virus-associated cryoglobulinemic vasculitis 

7. Vasculitis associated with systemic disease 

  • Rheumatoid vasculitis 


Vasculitis with granuloma vs. no granuloma

- large vessel vasculitis 

- medium vessel vascuitis

- small vessel vasculitis

all large vessel vasculitis have granuloma

none of medium vessel vasculitis have granuloma

in small vessel vasculitis; only Wegener's granulomatosis & Churg-strauss syndrome have granuloma. all other small vessel vasculitis have no granuloma


Decribe Behcet's disease


  • Autoinflammation of arteries and veins of all sizes 
  • 2 per 1000 in Turkey (‘silk route’, turkey, middle eastern, china)
  • A genetic component 
  • Oral aphthous ulcers x3 in 12 months, Plus 2 of the following 4 features:
    • Ocular inflammation 
    • Genital ulcers 
    • Pathergy reaction (exaggerated skin response to minor trauma)
    • Skin lesions –pustules, erythema nodosum
  • Treatment: colchicine, steroids 
  • Associated with venous thromboses


Describe giant cell arteritis

  • >50yo Caucasians. peak 70-80yo. F>M. a/w polymyalgia rheumatica (PMR)
  • granulomatous inflammation of affected vessels with infiltration of lymphocytes, macrophages, and multinucleated giant cells.
  • can affect aorta, its major branches off the arch, external carotid, subclavian, axillary, temporal, ophthalmic, ciliary, occipital, and vertebral arteries.
  • Px: 
    • constitutional symptoms, insidious onset, headache, scalp pain, and temporal artery tenderness. jaw claudication (ischemia of the muscles of mastication). Fever, fatigue, and weight loss. 
    • ischemic optic neuropathy -> amaurosis fugax and blindness (permanent).
    • aortic aneurysm and dissection. Dilation of the aortic root -> aortic valve regurgitation and heart failure.
    • scalp or temporal artery tenderness and induration, reduced pulses and bruits, or aortic regurgitation and heart failure.
  • Ix:
    • elevated ESR, CRP.
    • temporal artery biopsy (gold standard): panarteritis, granulomatous inflammatory infiltrate, disruption of internal elastic lamina. abnormal upto 2/52 post steroids. 
    • +/- USS, CTA, angiography for subcranial disease "halo sign"
  • Mx:
    • steroids ASAP if suspected to preventn visual loss. Prednisone 1 mg/kg/d 2-4/52 with slow wean 10-20% Q2/52. once 10mg/d; taper 1mg/month for up to 2 years. IV pulse if active visual loss. If no improvement of inflamm markers, rethink diagnosis. 
    • Low-dose aspirin daily may help to reduce the risk of blindness
    • +/- methotrexate, IL-6 inhibitor 


ARA criteria for Takayasu arteritis

ARA criteria: 3 of the following 6

  • Age at disease onset <40 years
  • Claudication of extremities
  • Decreased pulsation of one or both brachial arteries
  • Difference of at least 10 mm Hg in systolic BP between arms
  • Bruit over one or both subclavian arteries or the abdominal aorta 



ARA criteria for giant cell arteritis


  • Age at onset > 50 years
  • Absence of exclusion criteria (eye, kidney, skin, peripheral nerve, lung, LN, disease; digital gangrene)
  • 3 of 11 points
    • New onset localised headache
    • Sudden onset visual disturbance
    • PMR (2)
    • Jaw claudication
    • Abnormal temporal artery (2)
    • Unexplained fever, anaemia
    • ESR 50 mm/hour
    • Compatible pathology (2) 


Mx of giant cell arteritis


  • Continuum with Takayasu arteritis? 
  • Severe headache 
  • Imaging useful – ultrasound, CT scan, MRI and PET
  • Bilateral long biopsies most sensitive 
  • Give steroids before biopsy
  • Risk of blindness only in first weeks
  • Try to limit steroid use to 2 years
  • Use low dose aspirin too 
  • Monitor with ESR and CRP 
  • 25% have large vessel involvement only eg axillary, subclavian
  • 14% have thoracic aortic aneurysms 


Characteristic sign on ultrasound for giant cell arteritis

halo sign

hypoechoic circumferential wall thickening due to vasculitic wall oedema


Difference between GCA & PMR on PET-CT scan

GCA: uptake of aorta is comparable to liver

PMR: uptake of shoulder is comparable to liver


Describe polyarteritis nodosa

- prevalence compared to MPA

- px

- association with other conditions

- ix 

- mx

- recurrence


  • systemic necrotising vasculitis of medium sized muscular arteries -> inflammation, luminal narrowing and stenosis, aneurysms, thrombosis 
  • Less common than microscopic polyangiitis, but Overlap syndrome with MPA is much more common 
  • 50yo. M>F
  • Px:
    • constitutional symptoms
    • skin, neurologic, MSK. renovascular > glomerular. rarely heart. no involvement of lungs.
    • Affects medium-sized vessels, mainly visceral arteries especially at bifurcations; aneurysms
    • Organ ischemia, infarction eg bowel and kidney (abdo pain)
    • Peripheral neuropathy
    • No glomerulonephritis, lung haemorrhage or systemic features
  • Ix: biopsy of medium-sized vessel (focal segmental panmural necrotizing inflammation), angiogram. ANCA negative
  • strong a/w hepatitis B (33%), HepC, HIV, hairy cell leukaemia.
  • a/w ADA2 deficiency (DADA2): affects skin, CVA. mx with TNFi & HSCT
  • Mx: steroids + cyclophosphamide/azathioprine, relapses uncommon. +/- antiviral, plasmapheresis if hepBsAg+.


Describe polyarteritis nodosa a/w ADA2 deficiency (DADA2)


  • First vasculitis syndrome due to mutation in a single gene 
  • Autosomal recessive mutations in the ADA2 gene 
  • Contrasts with SCID due to ADA1 deficiency 
  • Milder phenotype, vasculitis of small, medium arteries
  • Skin and CNS (CVA) affected most often; kidney also with renal artery stenosis, aneurysms 
  • Treatment with antiTNF agents, HSCT


Describe Kawasaki disease


  • acute, self limiting, small and medium sized vasculitis 
  • 0.02% children during or shortly after viral/bacterial infection
  • more common in Asians, M>F, 6month-5 years
  • Pathophys: unclear. involves neutrophils -> eosinophils -> cytokines, CD8+ T cells -> vascular muscular intima damage, arterial wall dilatation -> coronary artery aneurysms 
  • Diagnostic criteria: Infants, fever >5 days without obvious explanation together with 4 out of 5: 
    • Bilateral conjunctival injection
    • Oral mucosal changes
    • Peripheral extremities –erythema of soles, desquamation etc
    • Polymorphous rash
    • Cervical lymphadenopathy 
  • If untreated, 20% risk of coronary artery aneurysm 
  • Mx: aspirin (reduce inflammation and platelet activation) + intravenous immunoglobulin (within 10 days of onset reduce coronary artery aneurysm) +/- steroids 


Describe isolated CNS vasculitis


  • Rare
  • No specific criteria
  • CNS symptoms and signs
  • Diagnosed by angiography and leptomeningeal biopsy 


Vasculitis a/w ANCA, and vasculitis not associated with ANCA


ANCA found in systemic small vessel vasculitis

  • Wegener’s granulomatosis
  • Microscopic polyangiitis and overlap syndrome 
  • Churg-Strauss syndrome (50%, P-ANCA with MPO specificity) 
  • Some cases of drug-induced vasculitis
  • Some cases of rheumatoid vasculitis 

Not found in Polyarteritis nodosa 

  • Kawasaki disease
  • Isolated CNS vasculitis 
  • Henoch Schonlein purpura 
  • Cryoglobulinemic vasculitis 
  • Hypersensitvity/ Leucocytoclastic vasculitis 
  • Vasculitis secondary to viral infections