ASCULITIS AND THE LUNG PART 2 Flashcards
(21 cards)
VASCULITIS
Clinicopathologic process → — of & — to —
Lumen compromised → — of tissues supplied by involved vessels
General:
* Any type, size, & location
of vessel
* Disease Expression
Varies
▪ — predisposition
▪ Environmental exposures
▪ — mechanisms
associated with — response to antigens
Pathophysiology / Pathogenesis:
* — Immune complex
formation / deposition
* Production —-
* Pathogenic — Response & —
Formation
inflammation and damage of blood vessels
ishcemia
genetic and enverinmental
immune response
pathogenic immune
Anti Neutrophilic
Cytoplasmic Antibodies
t lymphocyte and grauloma
info :
immunologic causes of vasculitis:
immune complex as SLE
ANCA
antibody attack as good pasture syndrome
cell mediated as organ rejection
immune complex vasulitis formation / deposition :
* — vasculitis (Henoch Schönlein)
* — vasculitis
* — sickness & – vasculitis syndromes
* HCV - associated — vasculitis
* HBV - associated vasculitis
IgA
lupus
serum and cuteanous
cryoglobulinaemic
ANCA and vasculitis:
* ANCAs = a group of — detected in a number of — disorders, but particularly associated with —
vasculitis
* Main classes
– — -ANCA( — )
– —ANCA
* 3 primary vasculitides associated with ANCA positivity:
– Granulomatosis with Polyangiitis ( —
granulomatosis) [90%+]
– — Polyangiitis
– — granulomatosis with polyangiitis (Churg
Strauss)
Active granulomatosis with polyangiitis in the absence of ANCA
Absolute height of antibody titres does not correlate well with disease—
Granulomatosis with polyangiitis in remission may continue to have high ANCA levels for years
autoanitbodies
autoimmune
sustemic
p ( preinculear )
c
wegeners
microscopic
estinophilic
disease activity
pathogenic t lymphocyte response and granuloma formation:
* — cells (ECs) can express —
molecules following activation by — such as —-
* Allows EC’s to participate in — reactions such as interaction with — in a manner similar to antigen presenting macrophages
* ECs can secrete — which may activate — & initiate / propagate — immunologic processes within the blood vessel
* IL1 & TNFα potent inducers of — and – which may enhance — of leukocytes to ECs in vessel wal
endothelial
human leukocyte antigen (HLA) class II
cytokines
interferon (IFN) γ.
CD4+ T lymphocytes
intelrukins
t lymphocyte
in sity
ELAM1 & VCAM1
adhesion
grnaulmatosis w polyangiitis :
— and — resp tract w glomerulonephritis and variable degrees of disseminated vasculitis
* — vasculitis — & — with — formation
▪ Intravascular or extravascular [rare on renal biopsy]
* Any organ can be involved with vasculitis, granuloma, or both
▪ ENT 73% →93%; Lung 45% → 85%; Renal 77%
* TNFα production from peripheral blood — cells and — cells ↑
* 90% positive —- ANCA
* At Biopsy — Disease Beware
▪ Extranodal natural killer (NK) / T-cell lymphoma (nasal type)
▪ Cocaine [+/- levamisole adulteration] induced tissue injury
▪ Lymphomatoid Granulomatosis [EBV]
▪ Effects of Pre-biopsy treatment
upper and lower
necrotising
small arteries and veins
granuloma formation
mononuclear cells and cd4+ t cells
anti-proteinase 3
midline destructive disease
granulomatosis w polyangitis GPA) :
( — GRANULOMATOSIS; — ASSOCIATED VASCULITIS)
* Hallmark:
▪ Pauci-immune vasculitis of — to — sized vessels
▪ —- granulomatous inflammation
* Antineutrophil Cytoplasmic antibody (ANCA)
▪ — ANCA (—ANCA) directed against — is most specific for
GPA
▪ Some patients with GPA express — staining ANCA (— specific for — (MPO)
* Radiology
▪ CXR, CT Thorax (nodular densities, may cavitate), CT sinus
* Biopsy (only in — presentation)
▪ Lungs: — vasculitis, — necrotising granulomatous —
▪ Vessels: acute and chronic — with — necrosis of vessel
wall
wegner
ANCA
small and medium
necrotising
cytoplasmic
c
PR3
perinuclear
p
for myeolperoxidase
atypical
necrotising , parenchymal , inflamamtion
inflammtion w fibrnoid necrosis
clinical presentation:
* Recurrent RTI’s, fever, night sweats, fatigue, lethargy,
weight loss, anorexia
* Ophthalmic
▪ Conjunctivitis, episcleritis
* ENT
▪ Chronic sinusitis, rhinitis, epistaxis
* Pulmonary
▪ Pulmonary infiltrates, cough, haemoptysis, dyspnoea,
diffuse alveolar haemorrhage due to alveolar
capillaritis
- Musculoskeletal
▪ Myalgia, arthralgia - Renal
▪ Crescentic necrotising
glomerulonephritis - CNS
- Cutaneous
▪ Vasculitis ulcers - Cardiac
▪ Pericardial rub
estinophilic granulomatosis w polyangiitis aka —
has — , — and – estinophilia , — granuloma formation and vasculitis of — organ system
* — , —- , —- Multiplex
* — & —
* Eosinophilia, which reaches
levels > — cells/μL in >80%
of patients
* 48% of patients have —
ANCA ….usually anti- —
* — , — necrotising, granulomatous vasculitis, affects — to — sized vessels, associated with severe — and — and — eosinophilia
* — associated vasculitis (like GPA and microscopic polyangiitis)
charge strauss
asthma , peripheral and tissue
extravascular grnulmoa
multiple organ
asthma , pulmonary infiltrates , moneuritis
>1000
circulating ANCA
anti-
myeloperoxidase
rare systemic
small and medium
severe asthma and blood and tissue
Inca associated
estinophilic EGPA clinical presentation:
▪ Allergic — / asthma
▪ Eosinophilic — disease (e.g. eosinophilic — , — )
▪ Vasculitis (small and medium sized vessels with
granulomatous inflammation)
* Investigations
▪ Bloods: ESR, CRP, U&E, FBC (eosinophilia), IgE, rheumatoid
factor positive (low titre), —ANCA +
▪ Bronchoscopy: — fluid shows raised eosinophils
* Constitutional symptoms
▪ Malaise, fever, weight loss, myalgia
* Asthma
* Paranasal —
* Allergic rhinitis:
–> ▪ Recurrent —
—> ▪ —-
* Pulmonary symptoms
▪ Cough, haemoptysis
rhinitis
infiltrative
estinophilic pneumonia , gastroenteritis
p-ANCA
lavage
paranasal sinusitis
recurrent sinusitis
polyposis
more of EGPA:
* Arthralgia
* Skin
▪ Purpura, bullae, nodules, digital ischaemia
* Cardiac
▪ Myocarditis, pericarditis, MI
* GIT:
▪ Eosinophilic —
* Peripheral neuropathy:
▪ — multiplex
gastroenteritis
Mononeuritis
microscopic polyangiitis:
is — vasultiits w — w few or no — complexs
affects —- as —-
-Very Similar to
Granulomatosis
with Polyangiitis
-Golmerulonephritis
79%
-Haemoptysis 12% Skin Nerves Gut
-ANCA 75%[—- ]
necrotisizng
no granulomas
immune complexes
small vessels ( capillaries , venules , arterioles )
Myeloperoxidase
polyarteritis nodosa:
is — system w — vasulitis of —- and — sized —- as — and —-
* Does not involve —
– — vessels may be involved;
* No — , significant —
or —
* Vessel involvement segmental involve —
* May spread — to involve
adjacent veins
* Histopathology – — dependant
– Acute
▪ —- infiltrate all
layers of the vessel wall & perivascular areas
▪ Intimal — and — of vessel
wall
– Subacute
▪ — cells infiltrate as lesions progress
to
– Chronic stages
▪ — of the vessels ensues with
compromise of the — , — , — of
the tissues supplied by the involved vessel +/- — .
– Healing Stage
▪ — deposition, which may lead to further
occlusion of the vessel lumen.
▪ Aneurysmal dilations up to — cm in size along the
involved arteries are characteristic of polyarteritis
nodosa.
multi system
necrotitzing
small and medium sized muscular arteries
renal and visceral arteries
pulmonary arteries
bronchial vessels
no granuloma , estinophilia or allergies
bifurcation
circumferentially
time
Polymorphonuclear neutrophils
intimal proliferation and degenration
mononuclear cells
fibrioid necrosis
lumen, thrombosis, and infraction
haemorrhages
collagen
1 cm
giant cell arteritis and polymylagia rheumatic:
Temporal Arteritis
* Inflammation of — & — sized —
* 1+ branches — artery - particularly — artery
* — disease that may involve arteries in multiple locations, particularly the — and its —
* Association with —
Polymyalgia Rheumatica:
* Stiffness, aching, and pain in the muscles of the neck, shoulders, lower back, hips, thighs
* Occurs in — , but may be seen in 40–50% of patients with —
* ~10–20% of patients who initially present with features of isolated
PMR later go on to develop giant cell arteritis
medium and large sized arteries
carotid artery
temporal
systemic
aorta and main branches
HLADR4
isolation
giant cell arteritis
GIANT CELL ARTERITIS
* Increased expression in
the — of —
* Protein recognized by
—- →induces — & — polarization
* IFNγ producing —
cells and IL17producing
— cells
* Ultrasonography of the
temporal artery for
diagnosis?
TAKAYASU’S ARTERITIS:
—- vessel walls, — , post-stenotic
dilation, aneurysm formation, occlusion
Increased — circulation
Complete imaging of the aorta & major
branches essential
Tissue for diagnosis rarely available
Exclude — related disease [potential cause
of aortitis & periaortitis ] — positive plasma cells, storiform pattern
of fibrosis, obliterative phlebitis
endothelium of jagged 1
CD4+
Th1 + Th17
irregular , stenosis
collateral
IgG4
IgG4
IGA VASCULITIS (HENOCH SCHONLEIN):
* —- immune
complex deposition
* Precipitants
▪ —- respiratory
tract infections,—,—,—,—
* Symptoms
▪ —-
▪ — Pain
▪ —- [
Glomerulonephritis ]
* ↑ IgA ~ — %
IgA
upper , drugs food insect bites and immunisation
arthralgia , abdominal pain , urinary
50%
CRYOGLOBULINAEMIC VASCULITIS
* — precipitable monoclonal - — immunoglobulins
* Hepatitis C, multiple myeloma, lymphoproliferative disorders, connective tissue diseases, infection, liver disease, idiopathic
– HepC antigens in vasculitic —
– Effectiveness of — therapy
– Hep C RNA & anti–Hep C antibodies in — cryoprecipitates
* Immune Complexes
– Hep C antigens, polyclonal Hep C– specific IgG & monoclonal IgM rheumatoid
factor
* — 90% of patients
cold
polyclonal
skin lesions
antiviral
serum
Hypocomplementemia
SINGLE ORGAN VASCULITIS
RULE OUT SYSTEMIC DISEASE
Skin Nervous System (CNS PNS)
* Primary V Secondary
* PNS More likely to be —
* BUT exclude CNS
complications of long term
immunosuppressive therapy
* Primary CNS vasculitis
2ndary
PRIMARY CNS VASCULITIS [PCNSV]:
— DIFFICULT
* No Recognisable clinical —
* No accepted —
criteria
* No biochemical,
immunological, serological,
imaging investigations
diagnostic of PCNSV
Big Clinical Categories
* Encephalopathy acute / subacute
▪ Presenting as an acute confusional
state, progressing to drowsiness &
coma.
* MS-plus’ or ‘pseudo- MS’
▪ Atypical features
▪ Optic neuropathy & brainstem
episodes, seizures, severe &
persisting headaches
▪ — episodes or
hemispheric —-like episodes.
* Intracranial mass lesions
headache, drowsiness, focal signs and
often raised — pressure
No Diagnostic Test other than —
– Catheter — Sens &
Spec 25- 35% !
* Test to :-
– Exclude alternative
inflammatory, autoimmune,
infective, malignant disorders
– Identify clinically occult systemic
involvement & accessible
targets for biopsy
clinical syndrom
diagnostic
Encephalopathic episodes or
hemispheric stroke-like
intracranial pressure
biopsy
angiography
BRAIN BIOPSY
PRE-BIOPSY PLANNING
* —
* Block – cm 3
* Crest of a Gyrus
* White Matter
* Coagulate Post
Biopsy
* Unlikely to have
enough for IF
peripheral nerve vasulitis:
* Is the nerve clinically
involved ?
* — levels
* — your
Diagnostic Threshold
for Vasculitis
meningitis
1 cm
multiple levels
lower
VASCULITIS MIMICS
CLINICAL & PATHOLOGIC
Infectious Diseases:
* Bacterial endocarditis
* Disseminated gonococcal
infection
* Pulmonary histoplasmosis
* Coccidioidomycosis
* Syphilis
* Lyme disease
Neoplasms:
* Atrial myxoma
* Lymphoma
* Carcinomatosis
Coagulopathies / Thrombotic
Microangiopathies:
* Antiphospholipid syndrome
* Thrombotic thrombocytopenic
purpura
Drug Toxicity:
* Cocaine
* Levamisole
* Amphetamines
* Ergot alkaloids
* Methysergide
* Arsenic
VASCULITIS MIMICS
CLINICAL & PATHOLOGIC
Others:
* Sarcoidosis
* Amyloidosis – see Brain
* Lymphomatoid Granulomatosis
* Atheroembolic disease
Fibromuscular dysplasia:
* heritable disorders of —
* Segmental arterial — (SAM)
* Reversible cerebral — syndrome – see [CNS]
connective tossue
mediolysis
vasoconstrictive
