VASCULITIS

Definition
Blood vessels inflammation and damage
Tissue ischemia
Primary vasculitis
Secondary vasculitis
(infections, viruses, tumors, collagen diseases:
RA, Sjögren’s syndrome, SLE, SSc, Myositis)

VASCULITIS
CLASSIFICATION
LARGE-MEDIUM-SIZED VESSELS
Takayasu’s arteritis
Temporal arteritis
MEDIUM-SMALL-SIZED VESSELS
Polyarteritis nodosa
Kawasaki’s disease
Churg-Strauss syndrome
Wegener’s granulematosis
SMALL-SIZED VESSELS
Schonlein-Henoch syndrome
Cryoglobulinemia
Goodpasture’s (anti-GBM) disease
Immune complex vasculitis (SLE, Serum sickness)
Microscopic polyangiitis

VASCULITIS
CLASSIFICATION
MISCELLANEOUS SYNDROMES
Behcet’s syndrome
Pyoderma gangrenosum

VASCULITIS
Pathogenesis - Immune complexes formation
Ag
Ab
WBC
Ag+Ab=IC
C
B-cell activation
RBC

Vasculitis with IC
Serum sickness
CTD
SLE
PAN
Virus hepatitis B in IC
Cryoglobulinemic vasculitis
Hepatitis C related IC in cryoprecipitates

Vasculitis with IC
Antigen excess
IC formation
Increased permeability of blood vessels
PLT & MC: histamine, bradykinin, leukotriens
Activation of complement
C5a – chemotaxis of PMNC
Degranulation of PMNC
Compromised blood flow
Tissue ischemia

Vasculitis with IC depositions
Henoch-Schonlein purpura
CVD
Serum sickness
HCV related mixed cryoglobulinemia
HBV related PAN

VASCULITIS
Pathogenesis - Anti-neutrophilic cytoplasmic Ab
pANCA – myeloperoxidase cANCA-proteinase 3

ANCA related
Wegener’s granulomatosis
Churg-Strauss syndrome
Microscopic polyangiitis
Necrotizing & crescentic GN
Goodpasture’s syndrome
Crohn’s disease , others IBD

ANCA associated vasculitis
TNFα, IL-1 induce translocation of azurophilic granules to membrane of monocytes and PMNC
Myeloperoxidase or proteinase 3 interact with extracellular ANCA
Monocytes and PMNC degranulate and release ROS, IL-1, IL-8
Tissue damage
No correlation between cANCA and WG activity

VASCULITIS
with granuloma formation
T lymphocyte accumulation

VASCULITIS
with granuloma formation
Ag or IC induce delayed hypersensitivity and cell mediated injury
EC activation
INF, IL-1
T-ly activation
TNF
IL-1
Adhesion molecules formation
ELAM-1
VCAM-1

T-ly response and granuloma formation
GCA
Takayasu-s
Wegener’s granulomatosis
Churg-Strauss syndrome

Suspicion of vasculitis
Systemic ilness
Purpura
Pulmonary infiltrates
Microhematuria
Chronic sinusitis
Mononeuritis multiplex
Unexplaned ischemia
GN

DD vasculitis
Infection
Neoplasia
Lymphoma
Coagulopathy
Drugs/toxins
Others

Takayasu’s Arteritis
Pulse-less disease
Incidence: 1-3/1 000 000/year.
Epidemiology: girls+young women
Japan, India, Africa, Asia, South America, Europe, US.
F:M=7:1. Age 10-50years (90% <30y)
Pathology: Involves aortic arch, descending aorta and its branches + AV involvement, coronary and pulmonary arteries
Panarteritis with granuloma (mononuclears) narrowed vessels and thrombus formation

Takayasu’s Arteritis
General: malaise, fever, night sweats, weight loss, arthralgia/arthritis
Vascular:
Arm claudication/numbness
Pulses changes/discrepancy
Hypertension
Renal failure
Aortic regurgitation (AR)
Pulmonary hypertension
Laboratory: anemia, ESR/CRP elevation
Diagnosis: angiography, MRI angiography
Treatment: steroids, cytotoxic drugs, control of hypertension, arterial reconstruction, AVR
Prognosis: 15 year survival 90%

Takayasu’s Arteritis

Giant Cell Arteritis/
Temporal arteritis

GCA
Medial and large vessels vasculitis
Branches of carotid artery
Temporal arteries
Strong association with PMR (50%)
Morning stiffness
Shoulder’s and pelvic pain
Isolated PMR is associated with GCA in 20%

GCA/PMR
Age >50
F>>M
Rare in blacks
6-30/100000
HLA DR4, HLA DRB1
IL-2, INF
CD4+
Panarteritis with mononuclear cells accumulation and giant cells, intimal proliferation
Ischemia of tissues

GCA
Fever
Headache
General signs
PMR
Scalp tenderness
Jaw claudication
Ischemic optic neuropathy, visual loss
Visceral ischemia, strokes
Aortic aneurisms, dissection
Anemia
High ESR
Liver enzymes elevation

GCA
Diagnosis
US Doppler
TA biopsy
14 days
Treatment
Cs (40-60 mg/d ~1 months)
Aspirin
MTX
Follow up: ESR

PMR
Diagnosis
Shoulder and hip pain
Stiffness
High ESR
Absence of signs GCA
Treatment
Cs (20mg/d)

Polyarteritis Nodosa (PAN)
Incidence: 5-9 to 80/1 000 000
Epidemiology: M:F=2-3:1, young patients
Pathology: fibrinoid necrosis medium/small arteries, aneurysms formation, mononuclear cells and PMNC infiltration, lumen thrombosis, obliteration of the lumen, sparing of pulmonary arteries. Segmental lesions
In kidney – arteritis without GN
Primary or secondary (RA, Sjogren’s syndrome, SLE, Hepatitis B, Hepatitis C, HIV, FMF, hairy cell leukemia)

Polyarteritis Nodosa
Clinical features:
General: severe disease, weight loss, mild to high fever, malaise
Musculo-skeletal (64%): arthralgia, asymmetric polyarthritis, myalgia
Skin (43|%): palpable purpura, ulceration, ischemic necrosis
Neural (50%): peripheral neuropathy, mononeuritis multiplex, CVA

Polyarteritis Nodosa
GIT: abdominal pain, mesenteric thrombosis, peritonitis, bleeding
Kidney (60%): hypertension, renal failure, proteinuria, hematuria – not glomerulonephritis, hemorrhage from microaneurisms
Cardiac (36%): CHF, MI
Eyes: retinal detachment, scleritis
Genito-urinary (25%): testicular, ovarian pain

PAN
Ischemic ulcers

PAN
Laboratory data: ESR↑, anemia, globulins↑,
30% HBS Ag+, aHCV+, 20-30% pANCA+ , abnormal urine
Diagnosis:
biopsy, angiography
Aneurysms formation

PAN
Prognosis: 5 year survival 15%-80%
Treatment:
Hepatitis neg: Steroids, Cyclophosphamide, Imuran, Methotrexate
Hepatitis pos: Antiviral treatment (Interferon, plasmapheresis, Ribaverin), Cs, plasma exchange
Relapse in 10%

Microscopic polyangiitis
Necrotizing vasculitis of small vessels
M>F, >55y
GN (80%)
Pulmonary capillaritis (12%) – hemorrhage
Cardiac and GIT involvement
Vascular lesions are similar to PAN, but in kidney – typical GN
ESR, anemia, leukocytosis, thrombocytosis, abnormal urine, pANCA pos+++
Diagnosis: kidney biopsy (pauci-immune GN)
Treatment: Cs, CYC
Relapse in 34%

Churg-Strauss Syndrome
Incidence: 1-2/1 000 000
Epidemiology: M:F=2:1
Pathology:
allergic necrotizing angiitis, eosinophils infiltration, extra-vascular granuloma formation
Small and medium sized vessels

Churg-Strauss Syndrome
Prodromal period: bronchial asthma
Second phase:
eosinophilia
Lóffler s-me - eosinophilic pneumonia
eosinophilic gastroenteritis
Third phase: systemic vasculitis

Churg-Strauss Syndrome
Clinical features:
General signs: fever, malaise, weight loss
Lung involvement: asthma, lung infiltrates, allergic rhinitis and sinusitis
GIT involvement: abdominal pain, diarrhea, bleeding
NS involvement: mononeuritis multiplex
Heart disease
Kidney involvement: GN
Skin: purpura
Arthritis

Churg-Strauss Syndrome
Peripheral lung infiltrates

Churg-Strauss Syndrome
Laboratory data: anemia, ESR ↑,
5 000-10 000 eosinophils/mm3, IgE ↑, pANCA + (70%)
Diagnosis: biopsy
Prognosis: 5 years survival-65%
Treatment: Steroids, Cyclophosphamide, Imuran

Wegener’s Granulomatosis
Incidence: 3/1 000 000
Epidemiology: M:F=1,2:1
Rare in blacks
Age >40 y
Pathology: necrotizing vasculitis of small arteies and veins, neutrophils accumulation and granuloma: upper airways (sinuses and nasopharyngs), lungs, kidney (pauci-immune GN no granuloma)
INF, TNF, CD4+ (Th1 type)
cANCA

Wegener’s Granulomatosis
General signs: fever, malaise, weight loss
Upper Respiratory Tract (95%): sinusitis, otitis media, nasal ulceration, septal perforation, subglottic stenosis
Often Staph aureus
Low Respiratory Tract (80%): Pulmonary infiltrates, nodules, cavities (cough, dyspnea, hemopthysis), bronchiectasia
Kidney (75%): Glomerulonephritis, hypertension, renal failure

Wegener’s Granulomatosis
Purpura (45%)→Necrotic ulcers
Arthritis (50-70%)
Eyes (52%): orbital/periorbital mass and damage, scleritis, vasculitis,
NS: peripheral neuropathy, central (33%)
Heart (8%): pericarditis, CHF, MI, arrhythmias
DVT and PE more then in healthy

Wegener’s Granulomatosis
Orbital and nasal granuloma
Pulmonary nodes
And cavitation

Wegener’s Granulomatosis
Laboratory data: leukocytosis, anemia, ESR↑, cANCA + (90%), abnormal urine, RF+, thrombocytosis
Diagnosis: nasal biopsy (granuloma), open lung biopsy (granuloma and vasculitis)
Renal biopsy is not specific

Wegener’s Granulomatosis
Prognosis: 5 years survival - 50-75%
Progressive renal failure
Late organ damage
Co-morbidities
Cancer (bladder)
Follow up: clinically, ANCA???
Treatment: CYC (oral/IV) and Cs, Imuran, MTX, MMF, Trimethoprim Sulfamethoxazole (Resprim)
Biological (RTX+, ETN-)

Henoch-Schőnlein Purpura
Incidence: 4-10/100 000
Epidemiology: M:F=1,2:1, age 4-14 years
Pathogenesis: IC vasculitis (Drugs? Infections?)
Pathology: small vessels necrotizing leukocytoclastic vasculitis, fibrinoid necrosis, IC, IgA and C3 deposition (skin, gut, kidney [glomerrular& tubular]), MNC infiltration

Henoch-Schőnlein Purpura
Clinical features:
General signs
Skin: palpable purpura (100%), ulceration (rare)
Arthritis, arthralgia (60%)
GIT vasculitis (85%) abd. pain, diarrhea, bleeding
Renal (IgA nephropathy) disease (10-40%) – segmental proliferative GN +/- crescents, IgA + C³ deposition (Berger’s disease) – hematuria, proteinuria

Henoch-Schőnlein Purpura
Purpura, Arthritis
Ischemic colitis

Henoch-Schőnlein Purpura
Laboratory data: elevated ESR/CRP, leukocytosis, mild anemia, hematuria, high IgA
Diagnosis: clinical +/- biopsy
Prognosis: good (except severe GIT vasculitis and IgA nephropathy)
Treatment: rest, tratement of underlying disease, NSAID, Cs, CYC – only in severe internal organ involvement

Essential Mixed Cryoglobulinemia
Cryo – cold-precipitable Ig (mono/polyclonal)
Systemic signs
Primary - rare
Secondary in most cases

Cryoglobulinemic Vasculitis
Biopsy:
Skin: Inflammatory infiltrate involving small blood vessels, fibrinoid necrosis, EC hyperplasia, hemorrhage, Ig and IC deposition
Kidney: Membranous GN
Hepatitis C specific Ig, monoclonal IgM RF++
ESR++, anemia, CRF, low C3/C4, HCV RNA+++, high IgM

Cryoglobulinemic Vasculitis
Hyperviscosity problems:
visual problems
TIA
neuropathy
Vasculitis:
purpura
arthritis
kidney involvement
glomerulonephritis
progressive renal failure
nephrotic syndrome

Cryoglobulinemic Vasculitis
Prognosis: poor, depends on viremia
Treatment:
plasmapheresis,
antiviral therapy (Ribaverin + Interferon α)
Cs = CYC

Behcet’s Disease
Epidemiology: Japan, Meddle East (Silk rood)
Family penetration
Clinical feature:
Oral aphthous ulcers (100%) – 3/year
Genital ulcerations (80%)
Eye inflammation (65%)-anterior/posterior uveitis, retinal vasculitis
Skin inflammation (70%)-(folliculitis-like, acne-like, erythema nodosum-like)
Vasculitis (arterial-CNS, venous – thrombosis superficial and deep)

Behcet’s Disease
Aphtha
Erythema nodosum
Hypopion

Behcet’s Disease
Laboratory data: HLA B51 pos.
Pathergy skin test
Prognosis: serious in uveitis - blindness, CNS vasculitis, thrombosis
Treatment: Colchicine
CS +/- MTX, Imuran, Salazopyrine
CS +Neoral
Thalidomide
Anticoagulants