Wegners Granulomatosis

Type of
Vasculature
Epidemiology

Pathology &
Pathogenesis

Clinical
Manifestation

Small arteries & veins

Granulomatosis vasculitis of
upper & lower Respiratory tract
3:100,000 cases
1 M : 1 F w/ mean age of 40 yrs
Necrotizing vasculitis
Intra/extra-vascular granuloma
Lung: multiple, bilateral,nodular
cavitary infiltrates
Sinuses & Nasopharynx:
inflammation, granuloma, &
necrosis w/ or w/o vasculitis
Renal: focal or segmental GN or
RPGN
aberrant cell-mediated immune
response
Chronic S. aureus nasal carriage
associated replase
Inc. secretion of IFN-g, TNF-a,
CD4+
Nose: Nasal ulceration -> saddle
nose
Ear: Serous otitis media
Pulmo: asymptomatic infiltrate or
cough, hemoptysis, dyspnea,
chest discomfort
Eye: sore eyes/red eyes,
dacryosystitis, ciliary vessel
vasculitis, retro-orbital mass
lesion
Skin: papules, palpable purpura,
subcutaneous nodules, ulcers
Cardio: pericarditis, coronary
vasculitis, cardiomyopathy,
mimics MI @ <40 y/o
CNS: wrist-drop (mononeuritis
multiplex), cerebral vasculitis
mimics CVA (stroke), cranial
neuritis
Renal: mild GN protienuria,
hematuria, rbc cast

Churg-Strauss Syndrome

Small & medium muscular

arteries, capillaries, veins &
venules
Allergic Angitis &
granulomatosis
1-3: million cases
1.2 M : 1 F mean age of 48 yrs
Necrotizing vasculitis w/
eosinophilic infiltration in any
organ w/ pulmonary
predominance
Strongly associated w/ Asthma
Other organs: skin, CVS, kidneys,
PNS, GI
3 Phases:
st
1 : Prodromal allergic rhinitis,
nasal polyps, asthma attacks
nd
2 : Eosinophilic (+) eosinophilia
in PBS, manifesting w/ Leoffler
syndrome
rd
3 : Vasculitis
Nonspecific manifestations: fever,
malaise, anorexia, wt loss
Severe asthmatic attack w/
pulmonary infiltrates
wrist-drop (mononeuritis
multiplex) first sign purpura
and subcutaneous nodules
along radial nerve destruction
Allergic rhinitis & sinusitis

PAN
(Polyarteritis nodosa)
Small & medium sized muscular
arteries
(renal & visceral arteries)
Mutlisystem necrotizing vasculitis
Inflammation of entire wall
Uncommon dse
th th
2 M : 1 F @ 4 -5 decade
classic PAN
Segmental & bifurcations &
branches of arteries
Polymorphonuclear
neutrophilic infiltrates in all
layers of vessel wall
Intimal proliferation &
degeneration of entire vessel
wall
Compromises lumen ->
thrombos formation -> infarct
Assoc. w/ Hairy Cell leukemia

MPA
(Microscopic Polyangitis)
Small vessels esp. capillaries &
venules
Necrotizing vasculitis w/ no or
few immune complexes
GN & pulmonary capillaritis
M>F w/ mean age of 57 yrs
Histologically similar to PAN w/
predilection for capillaries and
venules
Minimal immuglobin deposition

Classification Criteria:
Wt loss of >4kg since onset
Livedo reticularis
Testicular pain/tenderness
Myalgias, weakness, leg
tenderness
Mono/polyneuropathies
Development of HPN

Takayasus Artertis
(Aortic Arch Syndrome)

Medium & large arteries

Medium & large artery

Cranial/Temporal arteritis
F>M @ >50 y/o

Involved one or more branches of

carotid artery ( temporal, aorta
& its branches)
Closely assoc. w/ PMR
Panarteritis w/ inflammatory
mononuclear infiltrates w/ giant
cell formation
Ag driven disease (t-cell,
macrophage, dendritic cells)
CD4 activated @ adventitia
leading to macrophage
differentiation
IL2 & IFN-g progressive arterities

Renal: arteritis w/o GN, renal HPN

Liver: assoc. w/ HBV (10-30%)
Constitional: fever, malaise, wt
loss depending on organ
involved
Skin: purpura, Livedo reticularis
(mottled appearance),
gangrene
HPN
Chronic Kidney Dse

GCA & PMR

(Giant Cell Arteritis &
Polymyalgia Rheumatica)

5 most common:
1. Kidney Inflammation (80%)
2. Wt Loss (>70%)
3. Skin Lesion (>60%)
4. Nerve Damage (60%)
5. Fever (55%)
Gradual onset
Constitional: fever, wt loss,
musculoskeletal pain
Hemoptysis alveolar damage
Mononeuritis multiplex wristdrop
GI & cutanteous vasculitis
Splinter Hemorrhage
Muscle wasting

PMR: stiffness, muscular pain in

neck, shoulder, lower back, hip
& thighs w/ 40-50% w/ GCA or
10-20% of PMR progressing to
GCA
Both GCA & PMR:
Fever, Anemia, headache >50y/o
Malaise, fatigue, anorexia, wt
loss, sweat arthralgia
Temporal Artery: thickened &
nodular, pulsates early in dse
Scalp pain, jaw claudication &
tongue
Ischemic optic neuropathy
MI, Extemety claudication, stroke,
visceral Infarct

Inflammation & stenosis

1.2-2.6: million cases
Common among adolescent girls
& women Asians
Panarteritis
Aortic arches & branches usually
at origin
Intimal proliferation & fibrosis
Scarring & vascularization
Distruption & degeneration of
internal elastic lamina

Constitution S/Sx depending on

organ involved
HPN
Absent of pulse on branch
affected
Presence of bruit

Labratory

Wegners Granulomatosis

Churg-Strauss Syndrome

PAN
(Polyarteritis nodosa)

MPA
(Microscopic Polyangitis)

(+) c-ANCA
(antiproteinase-3)

(+) p-ANCA
(antimyeloperoxidase)

(-) ANCA

(+) p-ANCA
(antimyeloperoxidase)

(+) p-ANCA (myeloperoxidase)

Elevated ESR
Mild anemia & leukocytosis
Thrombocytosis
Mild hypergammaglobinemia
(+) RF

Diagnosic
Basis

Management
& Prognosis

CXR: nodular
densities/granulomas
predominately on lung base
Tissue Biopsy:
Pulmo. wedge biopsy
(highest yield)
Renal biopsy showing pauciimmune GN
3 Major Patho. Findings:
1. Parencymal necrosis
2. Vasculitis
3. Granulomatous
inflammation w/ mixed
cellular infiltrates
Education, vocational counseling
Physiotherapy
Supportive therapy
Prednisone improves
symptoms not course
(1mg/kgBW/day) Prednisone
to hydrocortisone @ 1:5
Cyclophosphamide
(2mg/kgBW)
Azathioprine (2mg/kg)
Methothrexate (start @
7.5mg/wk to 20-25mg/wk)
Mycophenolate mofetil (1g
BID)
Rituximab - biologic therapy

Eosinophilia >1,000 cell/ul

Elevated ESR, fibrinogen, aglobulin
Sputum smear: crushmann
spirals

Tissue Biopsy:
1. Eosinophilic infiltrates
2. Peri/extra vascular small
necrotizing granulomas
3. Nectrotizing vasculitis
4. Lung necrosis

Untreated 25% (5yr remission)

Treated favorable
o
Mortality 2 cardiovascular causes
Medications:
Prednisone
Cyclophosphamide for
unresponsive to Predinose

High ESR
Leukocytosis w/ PMN dominance
Hypergammaglobinemia
(inverted A:G ratio)
Elevated BUN/Crea unrelated to
dehydration or obstruction

Elevated ESR
Leukocytosis
Anemia
Thrombocytosis

Biopsy of nodular skin, testis,

nerve & muscle lesions
containing granulocytes

GCA & PMR

(Giant Cell Arteritis &
Polymyalgia Rheumatica)
(-) ANCA

Medication:
Prednisone &
cyclophosphamide - same as
Wegners
Antivirals for HBV
Anti-HPN

74% 5 yr survival rate

34% relapse rate
Mortality 2o to:
Pulmonary
GI
Cardiac
Renal
Medication:
Prednisone &
cyclophosphamide - same as
Wegners

(-) ANCA

Elevated ESR
Normocytic Hypochromic Anemia
Elevated Alk PO4
Elevated IgG
Creatine Kinase normal

High ESR
Mild Anemia
High immune globulin

Biopsy of Temporal artery (3-5cm

diameter)
Ultrasound helpful

Biopsy of tissue
Arteriography (contrast MRA):
showing corkscrew appearance
of affected artery & aneurismal
dilation of aorta

Medication:
Prednisone (40-60 mg/day or
1mg/kgBW) gradually
tapered to control symptom
Aspirin reduce ischemic
complications
Methotrexate reduce
steroid dose

Spontaneous remission
94% 5yr survival rate
o
Mortality 2 to:
CHF
CVA
Renal
Aneurysm rupture

Angiography: aneurysm of small

& medium sized arteries of
kidney, liver and visceral organs

Poor prognosis if untreated

o
Mortality 2 to GI or
Cardiovascular
10% replase rate

Takayasus Artertis
(Aortic Arch Syndrome)

Medication:
Prednisone (40-60 mg/day)
for acute S/Sx
Methotrexate (up to 25mg)
for refractory cases
Surgical & angiographic approach