Diseases of Blood Vessels I

Assoc. Prof. Dr. Gupalo(MD)

Department of Pathology
[Link] School of Medicine Anguilla

1
 Lecture Outlines:
 Vascular Wall Cells and their Response to Injury
 Inflammatory disorder of the blood vessels/vasculitis:
 Large vessel vasculitis
Temporal (giant cell) arteritis
Takayasu’s arteritis (pulseless disease)
 Medium vessel vasculitis
Polyarteritis nodosa (PAN)
Kawasaki’s disease
 Small vessel vasculitis
Microscopic polyangiitis(MPA)
Churg-Strauss Syndrome
Wegener Granulomatosis
Behcet Disease
Henoch Schonlein purpura (HSP)
Mixed cryoglobulinemia
• Infectious vasculitis
 The vascular wall

Blood vessels have three concentric layers.

Intima:
• consists of a single layer of endothelial cells
• Separated from media by internal elastic lamina
Media:
• Consists of smooth muscle cells
• The outer portion of the media is separated from the adventitia by the external elastic
lamina.
Adventitia :
• Lies external to media
3
• Consists of connective tissue with nerve fibers and vasa vasorum.
 Pathological changes in blood vessels
Narrowing/ Weakening
complete obstruction of
blood vessel wall

Slow Acute
(e.g., by (e.g., by thrombus/embolus)
atherosclerosis)

Atrophy / infarction Dilation, Dissection/rupture

4
 Disorders of blood vessels
Arteries Veins and lymphatics
•Arteriosclerosis • Varicose veins
•Aneurysms and • Thrombophlebitis
dissection • Phlebothrombosis
•Vasculitis • Superior and
•Hypertension inferior vena cava
•Raynaud syndrome
phenomenon • Lymphangits
• Lymphedema
•Tumors of blood
5 vessels
Vascular Wall Cells and their Response to Injury

Endothelial Cells
Normal endothelial function maintains vessel
wall homeostasis & circulatory function through:
Maintenance of a permeability barrier
Elaboration of prothrombotic, antithrombotic&
fibrinolytic mediators
ECM production
Modulation of blood flow & vasomotor tone
Regulation of inflammation
Regulation of cell growth
Vascular Wall Cells and their Response to Injury

Vascular Smooth Muscle Cells(VSMCs)

VSMCs - the dominant cell type of the vessel
media & can:
Migrate & proliferate in response to various
mediators (e.g., PDGF, endothelin, thrombin &
fibroblast growth factor-FGF)
Elaborate cytokines & GFs
Synthesize & remodel ECM
Cause vasoconstriction/dilation in response to
physiologic /pharmacologic stimuli
Intimal Thickening—A Stereotypical Response to
Vascular Injury
Regardless of the nature of the injury (e.g., traumatic,
inflammatory, toxic, infectious), injured endothelium &
underlying vessel wall heals by stimulating SMC ingrow &
ECM production intimal
thickening(neointima).
The neointimal cells have a proliferative & synthetic
phenotype distinct from the underlying media, and the cells
may derive from the vessel wall or circulating precursors.
• In small to medium-sized vessels (e.g., coronary artery),
such intima thickening can lumenal stenosis &
downstream tissue ischemia.
 Inflammatory disorders of
the blood vessels

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 Vasculitis
 Inflammation of the blood vessel wall.
 May affect arteries, veins, and capillaries (aka angiitis)
 The two most common pathogenic mechanisms of
vasculitis:
 [Link] main immunological mechanisms:
 (1) immune complex deposition
 (2) antineutrophil cytoplasmic antibodies
 (3) anti-endothelial cell antibodies (Kawasaki
Disease).
B. Direct invasion by micro-organisms
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 Etiopathogenesis of noninfectious vasculitis
Immunologic mechanisms
 Immune complex deposition
 Responsible for most cases***
 Deposition of immune complex Activation
of complement  Release of C5a
 C5a  chemotactic for neutrophil
 Neutrophils  damaged endothelium &vessel
wall  fibrinoid necrosis.
 Endothelial damage  thrombosis 
Ischemic damage to tissue involved.
 Example of IC mediated Vasculitis = Henoch-
Schonlein purpura
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Antineutrophil cytoplas mic antibodies (ANCAs)

ANCAs -circulating ab reactive with neutrophil cytoplasmic ag

A heterogeneous group of autoab, directed against constituents
(mainly enzymes) of neutrophil primary granules, monocyte
lysosomes & endothelial cells:
Anti-myeloperoxidase (MPO-ANCA)/perinuclear-ANCA
(p-ANCA) is directed against the lysosomal constituent
involved in generating oxygen-free radicals. Seen in
microscopic polyangiitis & Churg-Strauss syndrome.
Anti-proteinase 3 (PR3-ANCA)/cytoplasmic ANCA (c-
ANCA). is directed against a neutrophil azurophilic granule
constituent, associated with Wegener granulomatosis.
ANCA titers correlate with disease activity.
Detected by immunofluorescence
12
 Mechanism for ANCA vasculitis
 Drugs /cross-reactive microbial antigens induce ANCAs
Alternatively, neutrophil surface expression/release of
PR3 & MPO (e.g., in the setting of infections) incites
ANCA formation in a susceptible host.
Subsequent infection, endotoxin exposure/other
inflammatory stimuli elicit cytokines (TNF)
surface expression of PR3 &MPO on neutrophils & other
cell types.
ANCAs react with these cytokine-activated cells & either
cause direct injury (e.g., to endothelial cells)/induce
further activation (e.g., in neutrophils).
• ANCA-activated neutrophils degranulate & also cause
injury by releasing ROS endothelial cell toxicity
& other indirect tissue injuries.
Vascular sites involved with the mc vasculitis
 Large vessel vasculitis
Giant cell (temporal) arteritis
 Is the most common vasculitis**.
 Occurs in women > 50 years (Female > male)
 Vessel involvement::
 Typically involves the temporal artery, also
the vertebral and ophthalmic arteries.
 May lead to irreversible blindness due to
anterior ischemic optic neuropathy.
 Etiopathogenesis:
 T cell–mediated immune response to vessel
15 wall antigen(s) causing granulomatous
Giant cell arteritis:
Morphology.
Gross. Involved arterial
segments develop
nodular intimal
thickening (with
occasional thromboses)
that reduces the luminal
diameter.

16
 Temporal (giant cell) arteritis

Giant cell

 Micro:
Granulomatous vasculitis with
elastic tissue fragmentation;
MGCs are seen in up to 75% of
cases.
17 Intimal fibrosis with medial
 Giant cell (temporal) arteritis
Clinical features:
Fever, fatigue, weight loss
Unilateral headache, possible temporal
artery tenderness, jaw claudication.
Painful, palpably enlarged, and tender
temporal artery*
Generalized muscular aching and stiffness
(shoulders and hip)
 Temporary/permanent blindness*
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 Giant cell (temporal) arteritis
Investigations:
ESR: screening test of choice; markedly
elevated.
Temporal artery biopsy: definitive
diagnosis (positive in only 60% of cases)
Treatment:
Treat with high-dose corticosteroids before
confirmatory temporal artery biopsy to
prevent blindness.
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Takayasu’s arteritis (pulseless disease)
 Ak/as Aortic arch syndrome
 Is an inflammatory disease of vessels affecting
 the aorta and its major branches
 Seen in Asian women <40 years old.
 Vessel involvement:
 Typically involves the aorta* and the aortic
arch vessles* (carotids, subclavian) with
granulomatous thickening & narrowing of
aortic arch & proximal great vessels
 Can also involve: pulmonary, renal, coronary

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 Takayasu’s arteritis (pulseless disease)
Etiopathogenesis:
 Cell-mediated immunity involving CD4+ & CD8+
T cells may play a key role, as these cells support
the formation of granulomas & potentially
activate various proteases (MMPs) &other cells,
promoting chronic inflammation & fibrosis
2 stages of the disease:
Early inflammatory stage with nonspecific symptoms
& transmural inflammation
Later pulseless phase with hypertension, ischemia &
occlusive changes, including intimal fibrosis
Takayasu’s arteritis

Pathology:
Thickening of vessels ( aorta
& branches) with narrow
( stenosis) lumen decreased
blood flow.
Microscopic
Similar to/indistinguishable
22 from Giant Cell Arteritis
 Takayasu’s arteritis (pulseless disease)
 Clinical:
Subclinical/nonspecific symptoms at onset
 Constitutional symptoms (night sweats, LOW, fever)
Dizziness, syncope.
Absent upper extremity pulse (pulseless disease)**
Blood pressure discrepancy* between extremities: low in the
upper & higher in the lower(> 10 mm Hg)
Visual disturbances
Pulmonary artery involvement may lead to hypertension
 Limb fatigue & pain.
 Diagnosis:
 Laboratory
 Nonspecific, elevated ESR, CRP & IL6

23
Angiography:
Early: arterial wall thickening and enhancement
 Medium vessel vasculitis

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 Polyarteritis nodosa (PAN)/Periarteritis Nodosa
 Inflammation occurs in all layers of blood vessels.
 A systemic disease usually affecting middle-aged males.
 Vessel type involvement:
 Affects medium-sized & small muscular arteries*.
 Sites:
 Kidney, heart, liver, GIT, and skin vessels
 Spares pulmonary circulation.
Etiology:
 The pathogenesis of polyarteritis nodosa (PAN) is unknown
 Evidence for immune complexes–the induced disease is
confined to HBV-related PAN; the role of immune complexes
in non-HBV-related PAN remains unclear
 Associations:
 Can occur as a complication of hepatitis B/C; 10-45% of PAN
patients are positive for HBsAg
 Hypersensitivity to drugs (IV amphetamines).
 Pathogenesis:

25 Immune complex deposition (e.g., HBsAg / anti-HBsAg)
 Polyarteritis nodosa (PAN)
Pathology:
Transmural inflammation (involving all layers).
Lesion in the vessel wall may involve the
entire circumference/part of it
Fibrinoid necrosis
Consequences:
development of thrombosis  infarction
Weakening of vessel wall Aneurysms
(kidney, heart, and GI tract)
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 Polyarteritis nodosa(PAN)
Morphology
PAN lesions are sharply demarcated and often induce
thrombosis, causing distal ischemic injury(infarction).
Acute lesions: sharply circumscribed arterial fibrinoid
necrosis (hyaline proteinaceous depositions in a
degenerating vessel wall) with associated neutrophilic
infiltrates that may extend into the adventitia.
Healed lesions: marked fibrotic thickening of the artery
with associated elastic lamina fragmentation &
occasionally aneurysmal dilation. (kidney, heart, and GI
tract).
 Lesions at different histologic stages may be present
concurrently.
 Neutrophils

fibrinoid necrosis
PAN. Fibrinoid necrosis with prominent neutrophilic and
28lymphocytic infiltration
PAN. Segmental fibrinoid necrosis and thrombotic occlusion of the
lumen of this small artery. Part of the vessel wall at the upper right
(arrow) is uninvolved.
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 PAN: Clinical features
MC in young to middle-aged men
Signs & symptoms: due to ischemic damage.
Target organs:
Kidneys: Vasculitis/infarction  hypertension,
hematuria, albuminuria.
GI tract: Bowel infarction  abdominal pain, melena.
Skin: Ischemic ulcers and nodules.
Coronary arteries: aneurysms, MI
Systemic manifestation: fever, malaise, and weight
loss.
MC Cause of death: Renal failure.
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 Diagnosis requires a combination PAN
of clinical history & physical
examination to assess organ
involvement
 Laboratory findings:
 HbsAg positive in 30% of cases
 Hematuria with RBC cast
 Arteriography: microaneurysms
& spasms on arteriogram (string
of pearls appearance, rosary
sign)/biopsy of palpable
nodulations in the skin/organ
involved.
 Treatment:
 Untreated cases: fatal in mc
 Good response to
immunosuppressive
therapy(remissions/cures in 90%
31 of cases).
 Kawasaki’s disease
 Is also known as mucocutaneous lymph node
syndrome.
 Is an acute self-limited febrile illness of
infants& children (< 4 yrs).
 Is endemic in Japan, Hawaii
 One of the manifestations is vasculitis (coronary
artery).
 In other words:
 KD is a childhood vasculitis that mainly targets
coronary arteries.
 Coronary artery involvement:
32
 can lead to coronary thrombosis& AMI
Kawasaki’s [Link]
heart with giant coronary artery
aneurysms of the right coronary
and left anterior descending
arteries.
Micro. Thrombosed aneurysm of
the CA along with panvasculitis.

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 Kawasaki’s disease
Clinical findings:
High fever
Erythematous rash of trunk & extremities with desquamation
of the skin.
Mucosal inflammation: cracked lips, oral erythema
Erythema, swelling of hands & feet.
Localized lymphadenopathy (cervical adenopathy)
MCC of an acute MI in children
Lab:
Neutrophilic leukocytosis
Thrombocytosis: characteristic finding
High ESR
abnormal ECG (e.g., acute MI)
34 
Treatment: IV immunoglobulin and aspirin.
A

Kawasaki disease (A) Bilateral, conjunctival injection. (B)

Strawberry tongue & bright red, swollen lips with vertical cracking &
bleeding. (C) Erythematous rash involving perineum. (D) Erythema
of the palms. (E) Erythema of the soles & swelling dorsal feet. (F)
Desquamation of the fingers. (G) Erythema and induration at the site
of a previous vaccination with Bacillus Calmette–Guérin (BCG). (H)
Perianal erythematous desquamation.
 Small vessel vasculitis

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 Small vessel vasculitis
Microscopic polyangiitis(MPA)
Also Hypersensitivity (leukocytoclastic) vasculitis
A primary systemic vasculitis of vessels smaller than
those involved in PAN.
Slight male predominance (mfr of 1.8:1)
Average age of onset:50–60 years
 Typical clinical features include pulmonary vasculitis,
pauci-immune glomerulonephritis, and palpable purpura.
Often also has nerves, GIT & musculoskeletal
involvement.
Often classified as a form of ANCA-associated
vasculitis.
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The exact etiology has yet Pathogenesis
 of MPA
to be fully understood.

Triggers: environmental factors &ANCAs.

Environmental triggers

Drugs: aspirin/penicillin/thiazide diuretics

Infectious organisms: strep/staph infections, TB, viral disease

Tumor proteins(e.g., in lymphoproliferative disorders)

This can either immune complex deposition/ may trigger secondary
immune responses (e.g., the development of p-ANCAs) that are ultimately
pathogenic.
Most lesions are pauci-immune (devoid of immune complexes).
Anti-neutrophil cytoplasmic antibodies (ANCA)
The majority of MPA have positive MPO–ANCA (p–ANCA)
ANCA activates neutrophil production of proinflammatory cytokines such
as IL-1 & TNF-α.
Stimulation of IL-1 & TNF-α producing ROS & release of lytic
enzymes.
These two processes detachment & lysis of the endothelium.
 Microscopic polyangiitis
Morphology
 Necrotizing glomerulonephritis (90% of patients)
& pulmonary capillaritis are particularly common.
Biopsies of palpable purpura(seen in 30–40% of
the patients) show leukocytoclastic vasculitis,
with neutrophilic infiltration of the small-caliber
vessels in the superficial dermis, fibrinoid necrosis
& leukocytoclasia (disintegration of neutrophil
nuclei into fragments/nuclear dust.
Little or no immunoglobulin deposition is seen in
most lesions("pauci-immune").
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 Microscopic polyangiitis
• MPA affecting a small
artery of the small
intestine shows
transmural infiltration
by leukocytes,
including numerous
neutrophils.
• There is extensive
leukocytoclasia
characterized by
nuclear karyorrhectic
fragments admixed
with intact leukocytes.
• Note the fibrinoid
40
necrosis (arrows).
 Microscopic polyangiitis

Palpable purpura in dependent areas consistent with

leukocytoclastic vasculitis. Perivascular inflammation shows
infiltration of neutrophils, fibrin deposition and nuclear dust
 Microscopic polyangiitis
Clinical features
• Constitutional symptoms
• Renal (∼ 90%): pauci-immune
glomerulonephritis with hypertension
• CNS (∼ 70%)-cerebral infarction
• Lungs (∼ 50%): pulmonary vasculitis → diffuse alveolar
hemorrhage → hemoptysis
• Skin (∼ 40%): palpable purpura, nodules, necrosis
• Gastrointestinal: abdominal pain (∼ 50%), GI bleeding (∼ 25%)
• CVS- Pericarditis
• Disseminated vascular lesions of hypersensitivity angiitis can also
occur as a presentation of other disorders:
• Henoch-Schönlein purpura
• Essential mixed cryoglobulinemia
• Vasculitis associated with connective tissue disorders
• Tx: Cyclosporine &steroids induce remission & improve long-term
 Microscopic polyangiitis
DIAGNOSIS : primarily clinical & confirmed by biopsy.
Chest imaging is required for all patients with lower
respiratory symptoms.
• Laboratory studies
• Inflammatory markers: ↑ ESR, ↑ CRP
• CBC: leukocytosis, thrombocytosis, anemia
• Serology: ANCA (positive in 50–75% of patients)
• MPO-ANCA in > 50% of patients
• PR3-ANCA in ∼ 25% of patients
• Urinalysis: proteinuria, microscopic hematuria, erythrocyte
casts
• Biopsy of the involved organ:
• Absence of granulomas
• Fibrinoid necrosis with neutrophil infiltration
 Cutaneous small-vessel vasculitis

Occurs 7-10 days after certain medications

(penicillin, cephalosporins, phenytoin,
allopurinol)/infections (e.g., HCV, HIV).
Palpable purpura, no visceral involvement.
Immune complex–mediated
leukocytoclastic vasculitis; late involvement
indicates systemic vasculitis.
 Churg-Strauss Syndrome
(Allergic granulomatous angiitis)
Also eosinophilic granulomatosis with polyangiitis (EGPA)
A systemic, small to medium vessel, granulomatous vasculitis
associated with asthma, allergic rhinitis, lung infiltrates, peripheral
hypereosinophilia & extravascular necrotizing granulomas.
ANCA-associated vasculitides, characterized by a strong Th2-type
immune response.
Th2-associated cytokines (IL-4, IL-13, IL-5 )may precipitate severe
eosinophilia in CSS, while migration of EOS to inflammatory sites is
possibly mediated by eotaxin-3.
Involves small* & medium vessels of
upper/lower respiratory tract*
heart, spleen, peripheral nerves(e.g, wrist/foot drop), skin,
kidney(pauci-immune glomerulonephritis).
45 Morph. Vascular lesions resemble PAN but are also characteristically
 Churg-Strauss Syndrome
Diagnosed clinically by
(allergic granulomatous angiitis)
the presence of:
Asthma
Blood eosinophilia
exceeding 1,500/mm3
Vasculitis involving at
least 2 extrapulmonary
organs.
Labs:
peripheral eosinophilia,
high serum IgE, MPO-
ANCA/p-ANCA Eosinophilic vasculitis
 Renal involvement: consistent with Churg-Strauss
hematuria, proteinuria, syndrome
46 elevated serum
 Wegener Granulomatosis (WG)

 Also granulomatosis with polyangiitis(GPA)

A necrotizing vasculitis characterized by a triad of:
Acute necrotizing granulomas of the URT(ear,
nose, sinuses, throat) or the LRT(lung)/both
Necrotizing/granulomatous vasculitis affecting
small to medium-sized vessels most prominent in
LRT& URT but affecting other sites as well
Renal disease in the form of focal necrotizing,
often crescentic, glomerulonephritis
Highly associated with c-ANCA**
47
 Wegener Granulomatosis (WG)
Pathogenesis
Several complex interactions involving genetics & microbes are
implicated.
c-ANCA with autoantibodies directed against proteinase 3 antibodies
seen in 80%-90% of the cases with GPA & the remaining is perinuclear-
ANCA (p-ANCA) directed against myeloperoxidase antibodies.
Defective immune-regulatory responses to environmental insults such as
infection/autoantigens excessive production of Th1 &Th17
cytokines (IL 17, TNF, and IF-gamma) the development of an
inflammatory granulomatous vascular lesion.
ANCA in GPA reacts with proteinase 3 (PR3), an enzyme prevalent in
neutrophil granulocytes.
ANCA activates neutrophils, which increased adherence to
endothelium & induces their degranulation, which damages endothelial
cells.
 Wegener Granulomatosis

A
 A, A lung from a fatal case of WG.
Large necrotizing granulomas are
present. B&C, granulomatous
inflammation with lymphocytes,
epithelioid cells, and giant cells. C
The involvement is vascular&
49
 Wegener Granulomatosis
Clinical features
Persons mc affected by WG are middle-aged 40-50
yrs Male> females
Respiratory tract signs and symptoms dominate the
clinical picture:
Upper respiratory tract (nasopharynx, sinuses,
trachea)
Chronic Sinusitis, ulcers of nasopharyngeal mucosa.
Saddle nose deformity* : Nasal cartilage destroyed
Lower respiratory tract
Recurrent pneumonia with nodular lesions which
undergo cavitation

50
Kidney: Crescentic glomerulonephritis  renal
 Wegener Granulomatosis
Clinical features

Lab:
c-ANCA present in 90% of patients with active
disease (a good marker of disease activity)
Specific for WG
CXR: large nodular densities.
Diagnosis: Biopsy
Treatment:
Cyclophosphamide
Danger of hemorrhagic cystitis and Transitional cell
carcinoma
Steroids
51
Without treatment, 80% die within 1 year
 Microscopic Polyangiitis vs
Wegener’s Granulomatosis
Sign Wegener’s Microscopic
Polyangiits

Granulomas Present Absent

Nasopharyngeal Present Absent

inflammation

ANCA C-ANCA P-ANCA

 Buerger’s Disease
 Also known as Thromboangitis Obliterans.
 A peripheral vascular disease of smokers.
males < 40years old, heavy smokers
Israel, Japan, India.
Pathology:
 A T-cell hypersensitivity response to smoke-modified self-
antigens is implicated.
 Earliest change: Acute inflammation involving the small
to medium-sized arteries in the extremities (tibial,
popliteal & radial arteries).
 Inflammation of vessel  thrombus formation  lumen
obliteration ischemia  gangrene of the extremity.
 Inflammation also extends to adjacent veins & nerves.
53  Involvement of the entire neurovascular
 Buerger’s Disease
Morphology
Gross. Affect small & medium-sized vessels of the
extremities. Ischemia, cyanosis, redness, ulceration, dry/wet
gangrene with/ without autoamputation
Micro.
• Acute inflammation:
• Endarteritis - neutrophils at the internal elastic lamina
(IEL).
• Periarteritis - neutrophils around the arteries.
• Luminal narrowing due to thrombi
• Organizing thrombi = thickened tunica intima.
• Occluded vessels may be re-canalized.
• Typically, segmental thrombotic occlusion
 Buerger’s Disease

Buerger’s Disease. The image demonstrates gangrene of

55
the digits with autoamputation of the left middle distal
phalanx
 Buerger’s Disease

Thromboangiitis obliterans (Buerger disease). The lumen is

occluded by a thrombus containing abscesses (arrow) & the
vessel wall is infiltrated with leukocytes.
 Buerger’s Disease
Clinical findings:
Early manifestation:
Intermittent Claudication(muscle pain )in
feet/hands
Cramping pain in muscles after exercise,
relieved by rest
Late manifestation:
Painful ulcerations of digits
Gangrene of the digits often requiring
amputation.
 Raynaud phenomenon is often present
57
 Buerger’s Disease
 No specific diagnostic test/positive
serologic markers
 The angiographic findings in
Buerger's disease (e.g., "corkscrew,“)
are helpful but not pathognomonic
 Diagnosis is based on 5 criteria:
smoking history
onset before 50
 infrapopliteal arterial occlusive
disease
upper limb involvement/phlebitis
migrants
 absence of atherosclerotic RFs other
than smoking
Rx:
58 
early stages of vasculitis frequently
 Small-vessel vasculitis
Behcet syndrome
A multisystem auto-inflammatory immune
complex vasculitis of unknown origin
involving arteries & veins of all sizes and types.
Associated with HLA-B51serotype.
Increased incidence in people of Turkish and
Eastern Mediterranean descent.
Venular involvement & formation of
pulmonary & arterial aneurysms are unique to
Behcet disease.
Can be precipitated by HSV/parvovirus.
 Behcet Disease
Morphology
• Micro. Biopsy of the mucocutaneous lesions
shows a neutrophil-predominant reaction with
endothelial swelling, extravasation of RBCs
&leukocytoclastic vasculitis with fibrinoid
necrosis of the blood vessel walls.
• Thrombophlebitis: thrombi in vessel lumens,
perivascular inflammatory infiltrate.
• The presence of lymphocytic vasculitis represents
older lesions & neutrophilic vascular reaction is
considered the most predominant reaction in
Behcet disease.
• Vasculitis of vasa vasorum may result in the
 Behcet Disease Morphology

 Behcet Disease. (A, B, C) Samples of venulitis, including leukocyte-rich inflammatory cellular

reaction, also accompanied a small number of mononuclear leukocytes and eosinophils.
Inflammation is also marked in the perivascular tissue (H&E, x200). D, inset) Arteriolitis
(H&E, x400).
 Behcet Disease, Clinical features:
• Oral ulcerations/aphthae (95% of cases) on lips, gingival, buccal mucosa
& tongue, leave no scars
• Genital ulcers (90% of cases) on the scrotum, major & minor labia, form
scars when healed
• Acne-like papulopustular lesions on the face, upper trunk & extremities
• Erythema nodosum-like lesions, healing with hyperpigmentation
• Recurrent asymmetric mono/oligoarthritis, arthralgia, usually involving
lower extremities, resolves with no deformity/erosion
• Ocular involvement (50% of cases), mainly posterior/panuveitis & retinal
vasculitis
• Superficial & deep venous thrombosis
• GIT involvement: mild abdominal pain/emergency complications
(hemorrhage/perforation)
• Neurologic involvement (5% of cases): severe headache, cranial nerve
palsy, ataxia & hemiparesis
• Vasculitis with contemporary involvement of arteries & veins with
aneurysm formation
 Behcet Disease, Clinical features:

A B

• Oral–labial aphtha. B. Genital

ulcer localized in the vagina.C.
Retinal hemorrhages with pale
centers.
Treatment:
• Systemic Steroids
• Systemic Immunosuppressive
agents C
 Behcet Disease, Clinical features:

A. MR cerebral venography
(MRV). Occlusion of the left
sigmoid and transverse sinuses.
[Link]çet's disease, anterior uveitis
with hypopyon, seen as yellowish
A
leukocytic exudate in the lower part
of the eye’s anterior chamber.
 Henoch Schonlein purpura (HSP)
A rare nonthrombocytopenic lgA–mediated small-
vessel vasculitis of autoimmune hypersensitivity.
Seen in children (MC vasculitis in children), rare in
adults.
Etiopathogenesis:
Usually occurs following an upper respiratory
infection.
Caused by deposition of IgA-C3 immune
complexes in the vessel wall.
Vessels involved:
Arterioles, capillaries, and venules of
65
Skin, GIT, Kidney, MSK system.
 Henoch Schonlein purpura (HSP)
Clinically characterized by:
Palpable purpura over extensor aspects of arms
and legs.
commonly limited to lower extremities/
buttocks.
Involvement of
GIT  colicky abdominal pain, melena
Musculoskeletal system  Arthralgia
(nonmigratory) and myalgias
 Kidney  hematuria due to focal
proliferative GN.
66
Lung  rare
 Henoch Schonlein purpura (HSP)
Lab:
Neutrophilic leukocytosis
Deposition of IgA-C3 immune
complexes: in skin and kidney.
Rx: steroids

67
 Mixed cryoglobulinemia

Vasculitis due to mixed IgG and IgM immune

complex deposition.
 Cryoglobulins are immunoglobulins that
precipitate in the cold.
Often due to viral infections, especially HCV.
Triad of palpable purpura, weakness, arthralgias.
May also have peripheral neuropathy and renal
disease (e.g., glomerulonephritis).
 Infectious vasculitis
Localized arteritis may be caused by the direct
invasion of infectious agents, m.c. bacteria/
fungi(Aspergillus &Mucor species).
 Vascular invasion can be part of localized tissue
infection (e.g., bacterial pneumonia/adjacent to
abscesses)/ can arise from hematogenous seeding
of bacteria during septicemia /embolization from
sepsis of IE.
Vascular infections can weaken arterial walls,
culminate in mycotic aneurysms/induce thrombosis
and infarction.

69 Thus, inflammation-induced thrombosis of
Summary of Vasculitis
 Raynaud Phenomenon
Results from exaggerated vasoconstriction of digital &
sometimes facial arteries & arterioles, producing pain,
pallor & cyanosis.
Prolonged vasospasm can result in tissue necrosis.
Primary Raynaud phenomenon: in 3% to 5% of the
general population &mc affects young women
Exaggerated vasomotor responses to cold/emotion.
The clinical course is usually benign.
Secondary Raynaud phenomenon: vascular
insufficiency due to arterial narrowing induced by other
conditions (e.g., atherosclerosis, SLE, systemic sclerosis
[scleroderma]/Buerger disease).
 Raynaud Phenomenon

Raynaud's phenomenon. A, Sharply demarcated pallor of the

distal fingers resulting from the closure of digital arteries. B,
Cyanosis of the fingertips
Thank you