Vasculitis Flashcards
Pathogenesis of Vasculitis
Inflammation of BVs leading to:
- vessel wall thickening
- stenosis
- occlusion –>
- ischaemia
Large vessel vasculitis (2)
Takayasu arteritis
Giant cell arteritis
Medium vessel vasculitis (2)
Polyarteritis nodosa
Kawasaki disease
Small-vessel vasculitis
Microscopic polyangitis
Granulomatosis with polyangiitis (Wegener)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
Cryoglobulinemic vasculitis
IgA vasculitis (Henoch-Schonlein)
Hypocomplementemic urticarial vascilitis (Anti-C1a vasculitis)
Anti-GBM disease
ANCA-associated small vessel vasculitis
Microscopic polyangiitis
Granulomatosis with polyangiitis (Wegener)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss
Immune complex small vessel vasculitis
Cryoglobulinemic vasculitis
IgA vasculitis (Henoch-Schonlein)
Hypocomplementemic urticarial vasculitis (Anti-C1q vasculitis)
Anti-GBM disease
General presentation of Vaculitis
Fever
Malaise
Weight loss
Fatigue
Large vessel vasculitis:
- pathology?
- main differences?
- general symptoms
- investigations
Pathology: primary vasculitis causing chronic granulomatous inflammation predominantly of the aorta & its major branches
Difference:
-age of onset (TA before 50, GCA after 50),
-GCA mainly in temporal arteries
Signs & Symptoms:
-early on they are non-specific (Fever, malaise, night sweats, weight loss, arthralgia, fatigue),
-claudicant symptoms in upper & lower limbs
Investigation:
-CPR, PV/ESR elevated;
-MR angiography (thickened vessel walls & stenosis)
Results of untreated large vessel vasculitis
Vascular stenosis & Aneurysm
- reduced pulses
- bruits
What age is Takayasu Arteritis diagnosed at?
before 50
young women in 20s-30s
Where is Takayasu Arteritis most common?
East Asian countries
Signs & Symptoms of Takayasu Arteritis
early on they are non-specific:
low-grade fever, malaise, night sweats, weight loss, arthralgia, fatigue
claudicant symptoms in upper & lower limbs
if untreated - vascular stenosis & aneurysm (reduced pulses, bruits)
Investigations of Takayasu Arteritis
CPR, PV/ESR elevated
MR angiography: detect thickened vessel walls and stenosis
Treatment of Takayasu Arteritis
- prednisolone starting at 40-6mg
- gradually reduced
- methotrexate & azathioprine may be added
Pathology of GCA
Transmural inflammation of intima, media, adventitia of affected arteries
Patchy infiltration: lymphocytes, macrophages, multinucleated giant cells
mononuclear infiltration / granulomatous inflammation
Vessel wall thickening - arterial luminal narrowing - distal ischaemia
What age is GCA diagnosed at?
after 50
What is the most common form of systemic vasculitis in adults?
GCA
Signs & Symptoms of GCA?
Visual disturbances (50%) Headache: -continous -temporal/occipital areas, -focal tenderness on direct palpation Jaw claudication: -fatigue/discomfort of muscles during chewing/speaking -ischaemia of maxilalry artery Scalp tenderness
Temporal artery may be thickened, prominent, tender to touch
Constitutional: fatigue, malaise, fever
When to worry about GCA
new onset headache in >50
elevated CPR, PV/ESR
always always consider GCA
Diagnosis of GCA
raised inflammatory markers
temporal artery biopsy - ASAP
specificity of positive temporal artery biopsy
100%
sensitivity of temporal artery biopsy
15-40% (patchy involvement)
treatment of GCA if no visual impairment
40mg prednisolone
- start as soon as diagnosis is suspected (don’t wait for results of biopsy)
- gradually tapered over 2 years (majority resolve)
treatment of GCA if there is visual impairment
60mg prednisolone
- start as soon as diagnosis is suspected (don’t wait for results of biopsy)
- gradually tapered over 2 years (majority resolve)
% of GCA patients with permanent visual impairment
20%
General signs & symptoms of small-medium vasculitis
fever weight loss raised, non blanching purpuric rash arthralgia/arthritis mononeuritis multiplex glomerulonephritis lung opacities on XRay
ANCA associated vasculitis
+ NO granuloma
Microscopic polyangiitis (MPA)
ANCA associated vasculitis
+ WITH granuloma
+ NO asthma
+ NO Eosinophilia
Granulomatosis with polyangiitis (GPA) (= Wegener’s)
ANCA associated vasculitis
+WITH granuloma
+WITH asthma
+WITH eosinophilia
Eosinophilic granulomatosis with polyangiitis (EGPA) (=Churg-Strauss)
Non-ANCA associated vasculitis
+ WITH IgA dominant immune deposit
Henoch-Scnlein Purpura
Non-ANCA associated vasculitis
+NO IgA dominant immune deposit
+NO serum cyroglobulin
other non ANCA vasculitis (e.g. IBD)
Non-ANCA associated vasculitis
+NO IgA dominant immune deposit
+serum cyroglobulin
Cyroglobulinemia
Pathology behind GPA
Granulomatous inflammation of respiratory tract, small and medium vessels
Necrotising glomerulonephritis common
Pathology behind EGPA
Eosinophilic granulomatous inflammation of resporatory tract, small and medium vessels
Associated with Asthma
Pathology behind MPA
Necrotising vasculitis with few immune deposits.
Necrotising glomerulonephritis very common
Which ANCA is GPA associated with?
cANCA
Which ANCA is EGPA associated with?
pANCA
Which ANCA is MPA associated with?
pANCA
Which vasculitis is cANCA associated with?
GPA
Which vasculitis is pANCA associated with?
EGPA, MPA
Which vasculitis is PR3 ab mainly associated with?
GPA
Which vasculitis is MPO associated with?
EGPA
MPA
M:F ratio of GPA
age of GPA diagnosis
M:F 1.5:1
35-55y
ACR criteria for GPA classification
2 or more criteria nasal/oral inflammation: -painful/painless ulcers -or purulent/bloody nasal discharge abnormal chest radiograph: -nodules, fixed infiltrates/cavities urinary sediment -microhematuria (>5 RBC/high power field) -or red cell casts in urine granulomatous inflammation on biopsy: -histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular/ extravasscular area (artery/arteriole)
GPA antibodies
cANCA PR3
Investigation of GPA
Raised inflammatory markers: CRP, PV/ESR Anaemia of chronic disease U&E for renal involvement Urinalysis CXR Biopsy of affected area: skin, kidney Immunology: cANCA, PR3
Management of ANCA Associated Vaculitis (GPA, EGPA, MPA)
localized/early systemic: methotrexate & steroids (?azathioprine & steroids)
Generalised/systemic:
-cyclophosphamide + steroids (1st line)
-rituximab + steroids (alternative)
-plasma exchange if creatinine > 500
-followed by azatioprine with alternatives being methotrexate
Refractory: IV immunoglobulins, rituximab
ACR criteria for EGPA
4 or more of:
asthma: wheezing
eosinophilia of more than 10% in peripheral blood
paranasal sinusitis
pulmonary infiltrates (may be transient)
histological proof of vasculitis with extravasular eosinophils
mononeuritis multiplex/ polyneuropathy
EGPA Investigation
Inflammatory markers: CRP, PV/ESR raised if chronic disease: check anaemia U&E for renal involvement urinalysis for renal involvement CXR biopsy of affected area - skin, kidney
EGPA antibodies
pANCA, MPO
% of MPA patints with necrotising glomerulonephritis
90%
MPA Investigation
Inflammatory markers: CRP, PV/ESR raised if chronic disease: check anaemia U&E for renal involvement urinalysis for renal involvement CXR biopsy of affected area - skin, kidney
MPA antibodies
pANCA, MPO
Pathology behind HSP (Henoch-Schonlein Purpure)
Acute IgA mediatd disorder causing generalized vasculitis, involving the small vessels of the: skin, GIT, kidneys, joints, rarely the lungs or CNS
Age of HSP
children common
commonly history of URTI a few weeks ago
Signs & Symptoms of HSP
Purpuric rash over the buttocks & lower limbs
abdominal pain
vomiting
joint pain
treatment of HSP
self-limiting condition
no specific treatment
settles over weeks-months
