Small vessel vasculitides
Introduction
Large arteries are the aorta and its major branches, medium arteries defined as the main
visceral arteries and their branches, small vessels are small intraparenchymal arteries,
arterioles, capillaries and venules.
•Small: (<50μm diameter)
-ANCA-associated (GPA, MPA, EGPA)
-Immune complex-mediated: hypersensitivity, mixed cryoglobulinemic, IgA
vasculitis, hypocomplementemic urticarial (anti-C1q), anti-GBM (capillary only).
•Medium: (50-150μm in diameter, contain muscular walls, located principally in the deep
reticular dermis, near the junction of the dermis and subcutaneous tissues, main visceral
arteries and veins such as renal, mesenteric and coronary arteries).
-PAN
-Kawasaki
-TAO (Buerger)
•Large: (aorta and its branches)
-GCA
-TAK
•All sizes and types
-Behçet
-Cogan
•Single-organ vasculitis: LCV, organ-limited PAN, PVCNS.
*Vasculitis concerns inflammation of the blood vessel wall resulting in narrowing or
occlusion of the lumen and aneurysm formation. Vasoocclusion is a temporary blockage of a
vessel (ex. by clots or sickled cells), while vascular obliteration is its permanent closure due
to structural damage or scarring (endotheliopathy).
*Small-vessel will more likely cause purpura (palpable or not), while medium-vessel will
cause livedo reticularis, ulcers, microaneurysms/stenosis.
*Small- and medium-sized vessel vasculitides are necrotizing (except TAO), dominated by
neutrophil cell infiltration.
*granulomatous are LVV + GPA/EGPA (but LVVs are not necrotizing).
Histology general findings: 1) Infiltration of the vessel wall by immune cells, 2) Fibrinoid
necrosis of blood vessel walls, 3) Leukocytoclasis (debris of PMNs).
Skin biopsy: the essential feature in any form of cutaneous vasculitis is the
disruption of architecture by an inflammatory infiltrate within and around the vessel walls.
The optimal time for skin biopsy is 24-48h after the appearance of a lesion. The cellular
infiltrates in cutaneous vasculitis are usually composed of a combination of neutrophils and
lymphocytes, but most cases demonstrate a predominance of one cell type or the other.
Leukocyte–EC interaction preferentially occurs in postcapillary venules. It is
noteworthy that many forms of small-vessel vasculitis are manifested by leukocytoclasis
localized in postcapillary venules, particularly in the skin. In that case, neutrophils don’t pass
the basement membrane but become fully activated followed by apoptosis and necrosis
within the vessel wall. On the contrary, arteriolitis cause nail infarcts, splinter hemorrhages
and Bywater’s lesions (in RV, SLE) or painful Osler’s nodules (endocarditis) on fingertips.
,The endothelium
is an active player, orchestrating the vascular tone by release of NO, ROS, arachidonic acid
metabolites in particular TxA2 and prostaglandin H2. Endothelial cells differ in morphology
and function depending on their location in the body. Macrovascular endothelial cells are
different from microvascular ones and arterial are not identical to venous ones.
Microvascular ECs (ex. glomerular) reside on a basal lamina with sparsely distributed
pericytes around them, that have important functions in maintaining the integrity of the
microvasculature.
Activation of the endothelium
See ‘Basic immunology’.
ANCA-associated
Not all patients with these conditions are ANCA (+). PR3 and MPO, both serine proteases,
are constituents of the primary granules of neutrophils and monocytes. The mean age at
diagnosis is 55yrs. Increase in levels of ANCAs has been shown to precede relapses of the
associated disease.
Epidemiology
-GPA: 6.5-11/million, around 50yrs, Caucasians = 7x African, men = women.
-MPA: 4/million, more common than GPA in Asia. Mean age 60yrs, men = women.
-EGPA: incidence 0.5-4.2/million person-years, prevalence 10-18/million, men = women.
Causes
-GPA: chronic nasal carriage of Staphylococcus aureus is present in 60% compared with 20%
of controls and is associated with a relapsing course. Association with silica dust. a1-
antitrypsin (A1AT) deficiency: because A1AT is a natural inhibitor of PR3, the observation
that patients with A1AT deficiency are at increased risk for GPA suggests a potential
pathogenic role in this disease for deficient PR3 clearance from sites of inflammation.
-EGPA: associated with asthma and peripheral eosinophilia.
Criteria
*Note that mononeuritis multiplex is a criterion for EGPA.
, Clinical
Introduction
Large arteries are the aorta and its major branches, medium arteries defined as the main
visceral arteries and their branches, small vessels are small intraparenchymal arteries,
arterioles, capillaries and venules.
•Small: (<50μm diameter)
-ANCA-associated (GPA, MPA, EGPA)
-Immune complex-mediated: hypersensitivity, mixed cryoglobulinemic, IgA
vasculitis, hypocomplementemic urticarial (anti-C1q), anti-GBM (capillary only).
•Medium: (50-150μm in diameter, contain muscular walls, located principally in the deep
reticular dermis, near the junction of the dermis and subcutaneous tissues, main visceral
arteries and veins such as renal, mesenteric and coronary arteries).
-PAN
-Kawasaki
-TAO (Buerger)
•Large: (aorta and its branches)
-GCA
-TAK
•All sizes and types
-Behçet
-Cogan
•Single-organ vasculitis: LCV, organ-limited PAN, PVCNS.
*Vasculitis concerns inflammation of the blood vessel wall resulting in narrowing or
occlusion of the lumen and aneurysm formation. Vasoocclusion is a temporary blockage of a
vessel (ex. by clots or sickled cells), while vascular obliteration is its permanent closure due
to structural damage or scarring (endotheliopathy).
*Small-vessel will more likely cause purpura (palpable or not), while medium-vessel will
cause livedo reticularis, ulcers, microaneurysms/stenosis.
*Small- and medium-sized vessel vasculitides are necrotizing (except TAO), dominated by
neutrophil cell infiltration.
*granulomatous are LVV + GPA/EGPA (but LVVs are not necrotizing).
Histology general findings: 1) Infiltration of the vessel wall by immune cells, 2) Fibrinoid
necrosis of blood vessel walls, 3) Leukocytoclasis (debris of PMNs).
Skin biopsy: the essential feature in any form of cutaneous vasculitis is the
disruption of architecture by an inflammatory infiltrate within and around the vessel walls.
The optimal time for skin biopsy is 24-48h after the appearance of a lesion. The cellular
infiltrates in cutaneous vasculitis are usually composed of a combination of neutrophils and
lymphocytes, but most cases demonstrate a predominance of one cell type or the other.
Leukocyte–EC interaction preferentially occurs in postcapillary venules. It is
noteworthy that many forms of small-vessel vasculitis are manifested by leukocytoclasis
localized in postcapillary venules, particularly in the skin. In that case, neutrophils don’t pass
the basement membrane but become fully activated followed by apoptosis and necrosis
within the vessel wall. On the contrary, arteriolitis cause nail infarcts, splinter hemorrhages
and Bywater’s lesions (in RV, SLE) or painful Osler’s nodules (endocarditis) on fingertips.
,The endothelium
is an active player, orchestrating the vascular tone by release of NO, ROS, arachidonic acid
metabolites in particular TxA2 and prostaglandin H2. Endothelial cells differ in morphology
and function depending on their location in the body. Macrovascular endothelial cells are
different from microvascular ones and arterial are not identical to venous ones.
Microvascular ECs (ex. glomerular) reside on a basal lamina with sparsely distributed
pericytes around them, that have important functions in maintaining the integrity of the
microvasculature.
Activation of the endothelium
See ‘Basic immunology’.
ANCA-associated
Not all patients with these conditions are ANCA (+). PR3 and MPO, both serine proteases,
are constituents of the primary granules of neutrophils and monocytes. The mean age at
diagnosis is 55yrs. Increase in levels of ANCAs has been shown to precede relapses of the
associated disease.
Epidemiology
-GPA: 6.5-11/million, around 50yrs, Caucasians = 7x African, men = women.
-MPA: 4/million, more common than GPA in Asia. Mean age 60yrs, men = women.
-EGPA: incidence 0.5-4.2/million person-years, prevalence 10-18/million, men = women.
Causes
-GPA: chronic nasal carriage of Staphylococcus aureus is present in 60% compared with 20%
of controls and is associated with a relapsing course. Association with silica dust. a1-
antitrypsin (A1AT) deficiency: because A1AT is a natural inhibitor of PR3, the observation
that patients with A1AT deficiency are at increased risk for GPA suggests a potential
pathogenic role in this disease for deficient PR3 clearance from sites of inflammation.
-EGPA: associated with asthma and peripheral eosinophilia.
Criteria
*Note that mononeuritis multiplex is a criterion for EGPA.
, Clinical
