Vasculitis Flashcards
1
Q
Features of hypersensitivity vasculitis
A
- 3/5 of:
- Age > 16 years
- Temporal relationship to a drug
- Palpable purpura
- Maculopapular rash
- Perivascular neutrophils on skin biopsy
- May have minor visceral invovlement (always check urine)
- Usually no specific treatment required - stop drug
2
Q
Drugs associated with hypersensitivity vasculitis:
A
- Sulphonamides - furosemide, thiazides
- Penicillins
- Cephalosporins
- Allopurinol
- Phenytoin
3
Q
Clinical features suggestive of vasculitis:
A
- Palpable purpura
- Multiorgan disease + systemic features
- Pulmonary-renal disease (haemoptysis + haematuria) - half due to GPA or MPA
- Mononeuritis multiplex
4
Q
Differential diagnosis for vasculitis
A
- Thrombocytopaenia
- Infective endocarditis
- Septicaemia
- Cholesterol emboli
- Amyloidosis
- Atrial myxoma with emboli
- Mycotic aneursym with emboli
5
Q
Examples of large vessel vasculitis
A
- Giant cell arteritis
- Takayasi arteritis
Both associated with granuloma formation
6
Q
Examples of medium sized vessel vasculitis
A
- Polyarteritis nodosa
- Kawasaki disease
- Isolated CNS vasculitis
None associated with granulomas
7
Q
Examples of small vessel vasculitis
A
ANCA Associated
- Granulomatosis with Polyangiitis (GPA)
- Esoinophilic granulomatosis with polyangiitis
- Microscopic polyangiitis
Immune complex small vessel vasculitis
- Cryoglobulinaemic vasculitis
- IgA Vasculitis (HSP)
- Hypoconplementaemic urticarial vasculitis (Anti-C1q vasculitis)
8
Q
Features of Behcet’s disease
A
- Autoinflammatory disease of the arteries and veins of all sizes
- 2/1000 Turkish people
- Genetic component
- Oral ulcers x 3 in 12 months plus 2 of:
- Ocular inflammation
- Genital ulcers
- Pathergy reaction
- Skin lesions - pustules, erythema nodosum
- Treatment: colchicine, steroid
- Associated with venous thrombosis
9
Q
Features of Takayasu arteritis
A
- 3 of:
- Age of onset <40 years
- Claudication of extremeties
- Decreased pulsation of one of both brachial arteries
- Difference of of least 10mmHg in systolic BP between arms
- Bruit over 1 or both subclavian arteries or the abdominal aorta
- Primarily affects the aorta and its major branches
10
Q
ARA criteria for GCA:
A
- Age of onset > 50 years
- Absence of exclusion criteria (eye, kidney, skin, peripheral nerve, lung, LN, digital gangrene)
- 3 of:
- New onset localised headache
- Sudden onset visual disturbance
- PMR (2)
- Jaw claudication
- Abnormal temporal artery (2)
- Unexplained fever, anaemia
- ESR 50
- Compatible pathology (2)
Primarily involves aorta and its major branches - prediliction for the carotids and branches - particularly the superficial temproal artery
Important cytokines involved in the pathogenesis of GCA: IL 6, IL 17, interferon gamma
11
Q
Ultrasound findings of temporal artery in GCA
A
- Hypoechoic, circumferential wall thickening due to vasculitis wall oedema - halo sign
12
Q
Features of ANCA in lung disease
A
- 90% patients with CF, correlates with vasculitis, psuedomonas, worse lung damage
- 5% ILD - low level ANCA, often MPO-ANCA
- Also in some forms in suppurative lung disease
13
Q
Features of polyarteritis nodosa
A
- Less common than microscopic polyangiitis
- Medium sized vessels - mainly visceral arteries, especially at bifurcations; aneursyms
- Organ ischaemia, speen/bowel/kidney infarction
- Peripheral neuropathy
- No glomerulonephritis, lung haemorrhage or systemic features such as fever
- A/W Hepatitis B
- May respond to steroids alone
- Relapses uncommon
- Not associated with ANCA
- Overlap syndrome with MPA much more common (ANCA positive)
14
Q
Features of PAN associated with ADA2 deficiency (DADA2)
A
- First vasculitis syndrome defined due to mutation in a single gene
- AR mutations in the ADA2 gene
- Contrasts with SCID due to ADA1 deficiency
- Milder phenotype - vasculitis of small and medium arteries
- Skin and CNS (CVA) affected most often , kidney also with renal artery stenosis, aneursyms
- Treatment with anti-TNF agents, HSCT
15
Q
Features of Kawasaki disease
A
- Infants, fever > 5 days without obvious explanation with 4 of:
- Bilateral conjunctival injection
- Oral mucosal changes
- Peripheral extremeties - erythema of soles, desquamation etc.
- Polymorphous rash
- Cervical lymphadenopathy
16
Q
Features of isolated CNS vasculitis
A
- Rare
- No specific criteria
- CNS symptoms and signs
- Diagnosied by angiography and leptomeningeal biopsy
17
Q
What are the ANCA positive vasculitides:
A
- Granolomatosis with polyangiitis (Wegener’s)
- Microscopic polyangiitis and overlap syndrome
- Eosinophilic granulomatosis with polyangiitis (50%, P-ANCA with MPO specificityt)
- Some cases of drug induced vasculitis and some cases of rheumatoid induced vasculitis
18
Q
Practicalities of ANCA testing
A
- Diagnosis and exclusion of small vessel vasculitis
- ANCA - screen with indirect immunoflurescence - all IF-positive sera tested in ELISAs for both PR3- and MPO-ANCA
19
Q
Features of C-ANCA positive result:
A
- Cytoplasmic granular flurescence with central accentuation due to antibodies directed against proteinase 3 (PR3)
- 90% active generalised GPA, 30% active MPA
- Correlated with ENT, URT disease, high relapse rate
- High levels at presentation, fall with treatment
- Sometimes persistent high levels of PR3-ANCA when disease is obviously inactive
- Pathogenetic, 4 major conformation epitopes
20
Q
Features of P-ANCA positive result on ANCA testing
A
- Immunoflurescence staining (with enthanol fixed human neutroophils) - perinuclear with nuclear extension (artefact)
- Antibodies against myeloperoxidase (MPO)
- 70% active MPA, 10% active GPA
- Other types of P-ANCA in IBD, etc directed against elastase, cathepsin G, lactoferrin, HMG proteins
- A/W haematuria, GN, low relapse rate
- High levels at presentation, fall with treatment
- Usually MPO-ANCA disappear, never recur
- Pathogenetic
- Sometimes low levels in other autoimmune disease - burnt out glomerulonephritis, ILD, lung infection
21
Q
Other autoantibodies in GPA and MPA (not ANCA)
A
- ANA in 15%
- Lupus anticoagulant in 10%
- Anticardiolipin antibodies in 10%
- AntiGBM antibodies in 5%
Other antibodies occur more often with MPA
Not always contemporaneous with ANCA
22
Q
Features of EGPA
A
- History of asthma, pulmonary opacities, eosinophilia. Vasculitis may occur many years after presentation with asthma
- Usually affects skin, peripheral nerves, heart, possible bowel, kidney disease
- Only half have P-ANCA with MPO-ANCA
- ANCA does not correlate with disease activity
- May respond to steroids alone
23
Q
Drug-induced ANCA associated vasculitis - associated drugs
A
- Propylthiouracil and related drugs
- Drugs that cause SLE - hydralazine
- Allopurinol
- Suphasalazine
- Minocylcine
- Cefotaxime, ciprofloxacin
- Thioridazine, clozapine
24
Q
Features and management of drug-induced ANCA-associated vasculitis
A
- Usually after treatment for >18 months
- Usually P-ANCA, high MPO ANCA - may be anti-elastase and lactoferrin too
- MOA (in the case of PTU) - PTU accumulates in neutrophils and binds to MPO changing its structure
- Ranges from asymptomatic → crescenteric glomerulonephritis
- Treatment
- Withdraw causative agent, steroids for symptomatic relief
- If multiorgan disease - steroids +/- immunosuppression, ANCA level may persist for months
25
Q
Features of limited GPA
A
- Affects eyes, ears, nose, sinuses, upper and lower airway, large joint arthralgias
- Symptoms easy to overlook - good guide to diagnosis and disease activity
- ANCA positive in 70%
- 90% develop generalised disease with renal involvement
- Risk factors for renal disease not known
26
Q
Features of generalised GPA
A
- Rapidly progressive glomerulonephritis (segmental necrotising glomerulonephritis or pauciimmune glomerulonephritis)
- Urinary casts
- Conjunctival injection
- Alveolar haemorrhage, air bronchograms, cavitation
27
Q
Signficance of A1AT genotype and GPA
A
- Individuals with abnormal genotypes (MS, MZ, SS, ZZ) → more likely to develop GPA
- A1AT inhibits PR3 active site → abnormal genotypes result in uninhibited PR3 which is more immunogenic
- Z genotype → more severe disease with more organ involvement, more progressive disease, higher mortality
28
Q
Management of GPA & MPA
A
Induction:
- Glucocorticoids
- Cyclophosphamide
- Oral as good as IV (relapse rate may be lower with oral)
- Rituximab may be an alternative induction agent but RAVE trial excluded patients with renal failure and alveolar haemorrhage requiring IMV
- Switch to azathioprine at 18 months (aza superior to mycophenolate in ANCA positive vasculitis)
29
Q
Features of microscopic polyangiitis
A
- Range of vessels involved
- Arteries often not affected
- Usually have renal disease at presentation
- Pulmonary haemorrhage in 40%
- P-ANCA positive
30
Q
Features of primary pauciimmune necrotising glomerulonephritis
A
- Very common, particularly in elderly
- Glomerulonephritis (kidney only involved)
- P-ANCA positive
31
Q
Features of MPA/PAN overlap syndrome
A
- Approx half of all patients with MPA
- All have glomerulonephritis
- Often with bowel infarction or peripheral neuropathy
- P-ANCA positive
32
Q
Features of ANCA in Gastrointestinal disease
A
- P-ANCA in 70% ulceative colitis
- No correlation with disease activity, anatomic extent of disease or response to surgery
- P-ANCA in 10% Crohn’s disease
- More likely in UC-like disease
- ANCA testing can be combined with ASCA testing for antisaccharomyces antibodies
- Also 90% PSC, 70% chronic active hepatitis
33
Q
Features of aNCA in arthritis
A
- 20% ANCA positive in RA
- P-ANCA or atypical ANCA
- Various antigenic specificities
- May indicate rheumatoid vasculitis
34
Q
Histology features of GCA:
A
- Pan arteritis (CD4 lymphocytes, histiocytes, plasma cells)
- Giant cell granulomas (not always seen)
- Disruption of internal elastic lamina (not specific, but hallmark features that tends to persist even after steroid treatment) - also seen w/ aging and atheroma
- Patchy and skip lesions
- Thrombosed and stenosed vessels
