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Immunology > Vasculitis > Flashcards

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
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2
Q

Drugs associated with hypersensitivity vasculitis:

A
  • Sulphonamides - furosemide, thiazides
  • Penicillins
  • Cephalosporins
  • Allopurinol
  • Phenytoin
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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
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4
Q

Differential diagnosis for vasculitis

A
  • Thrombocytopaenia
  • Infective endocarditis
  • Septicaemia
  • Cholesterol emboli
  • Amyloidosis
  • Atrial myxoma with emboli
  • Mycotic aneursym with emboli
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5
Q

Examples of large vessel vasculitis

A
  1. Giant cell arteritis
  2. Takayasi arteritis

Both associated with granuloma formation

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6
Q

Examples of medium sized vessel vasculitis

A
  1. Polyarteritis nodosa
  2. Kawasaki disease
  3. Isolated CNS vasculitis

None associated with granulomas

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7
Q

Examples of small vessel vasculitis

A

ANCA Associated

  1. Granulomatosis with Polyangiitis (GPA)
  2. Esoinophilic granulomatosis with polyangiitis
  3. Microscopic polyangiitis

Immune complex small vessel vasculitis

  1. Cryoglobulinaemic vasculitis
  2. IgA Vasculitis (HSP)
  3. Hypoconplementaemic urticarial vasculitis (Anti-C1q vasculitis)
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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
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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
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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

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11
Q

Ultrasound findings of temporal artery in GCA

A
  • Hypoechoic, circumferential wall thickening due to vasculitis wall oedema - halo sign
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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
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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)
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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
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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
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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
  1. Propylthiouracil and related drugs
  2. Drugs that cause SLE - hydralazine
  3. Allopurinol
  4. Suphasalazine
  5. Minocylcine
  6. Cefotaxime, ciprofloxacin
  7. 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

Immunology (7 decks)

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