Wegners Granulomatosis Churg-Strauss Syndrome PAN

(Polyarteritis nodosa)

MPA

(Microscopic Polyangitis)

GCA & PMR

(Giant Cell Arteritis &

Polymyalgia Rheumatica)

Takayasus Artertis

(Aortic Arch Syndrome)

Type of

Vasculature Small arteries & veins

Small & medium muscular

arteries, capillaries, veins &

venules

Small & medium sized muscular

arteries

(renal & visceral arteries)

Small vessels esp. capillaries &

venules Medium & large arteries Medium & large artery

Epidemiology Granulomatosis vasculitis of

upper & lower Respiratory tract

3:100,000 cases

1 M : 1 F w/ mean age of 40 yrs

Allergic Angitis &

granulomatosis

1-3: million cases

1.2 M : 1 F mean age of 48 yrs

Mutlisystem necrotizing vasculitis

Inflammation of entire wall

Uncommon dse

2 M : 1 F @ 4th

-5th

decade

Necrotizing vasculitis w/ no or

few immune complexes

GN & pulmonary capillaritis

M>F w/ mean age of 57 yrs

Cranial/Temporal arteritis

F>M @ >50 y/o

Inflammation & stenosis

1.2-2.6: million cases

Common among adolescent girls

& women Asians

Pathology &

Pathogenesis

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+

Necrotizing vasculitis w/

eosinophilic infiltration in any

organ w/ pulmonary

predominance

Strongly associated w/ Asthma

Other organs: skin, CVS, kidneys,

PNS, GI

3 Phases:

1st

: Prodromal allergic rhinitis,

nasal polyps, asthma attacks

2nd

: Eosinophilic (+) eosinophilia

in PBS, manifesting w/ Leoffler

syndrome

3rd

: Vasculitis

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

Renal: arteritis w/o GN, renal HPN

Liver: assoc. w/ HBV (10-30%)

Histologically similar to PAN w/

predilection for capillaries and

venules

Minimal immuglobin deposition

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

Panarteritis

Aortic arches & branches usually

at origin

Intimal proliferation & fibrosis

Scarring & vascularization

Distruption & degeneration of

internal elastic lamina

Clinical

Manifestation

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 @ 4kg since onset

Livedo reticularis

Testicular pain/tenderness

Myalgias, weakness, leg

tenderness

Mono/polyneuropathies

Development of HPN

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 wrist-

drop

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

Constitution S/Sx depending on

organ involved

HPN

Absent of pulse on branch

affected

Presence of bruit

Wegners Granulomatosis Churg-Strauss Syndrome PAN

(Polyarteritis nodosa)

MPA

(Microscopic Polyangitis)

GCA & PMR

(Giant Cell Arteritis &

Polymyalgia Rheumatica)

Takayasus Artertis

(Aortic Arch Syndrome)

Labratory (+) c-ANCA

(antiproteinase-3)

(+) p-ANCA (myeloperoxidase)

Elevated ESR

Mild anemia & leukocytosis

Thrombocytosis

Mild hypergammaglobinemia

(+) RF

CXR: nodular

densities/granulomas

predominately on lung base

(+) p-ANCA

(antimyeloperoxidase)

Eosinophilia >1,000 cell/ul

Elevated ESR, fibrinogen, a-

globulin

Sputum smear: crushmann

spirals

(-) ANCA

High ESR

Leukocytosis w/ PMN dominance

Hypergammaglobinemia

(inverted A:G ratio)

Elevated BUN/Crea unrelated to

dehydration or obstruction

(+) p-ANCA

(antimyeloperoxidase)

Elevated ESR

Leukocytosis

Anemia

Thrombocytosis

(-) ANCA

Elevated ESR

Normocytic Hypochromic Anemia

Elevated Alk PO4

Elevated IgG

Creatine Kinase normal

(-) ANCA

High ESR

Mild Anemia

High immune globulin

Diagnosic

Basis

Tissue Biopsy:

Pulmo. wedge biopsy

(highest yield)

Renal biopsy showing pauci-

immune GN

3 Major Patho. Findings:

1. Parencymal necrosis

2. Vasculitis

3. Granulomatous

inflammation w/ mixed

cellular infiltrates

Tissue Biopsy:

1. Eosinophilic infiltrates

2. Peri/extra vascular small

necrotizing granulomas

3. Nectrotizing vasculitis

4. Lung necrosis

Biopsy of nodular skin, testis,

nerve & muscle lesions

containing granulocytes

Angiography: aneurysm of small

& medium sized arteries of

kidney, liver and visceral organs

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

Management

& Prognosis

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

Untreated 25% (5yr remission)

Treated favorable

Mortality 2o cardiovascular causes

Medications:

Prednisone

Cyclophosphamide for

unresponsive to Predinose

Poor prognosis if untreated

Mortality 2o

to GI or

Cardiovascular

10% replase rate

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

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

Mortality 2o to:

CHF

CVA

Renal

Aneurysm rupture

Medication:

Prednisone (40-60 mg/day)

for acute S/Sx

Methotrexate (up to 25mg)

for refractory cases

Surgical & angiographic approach