Attending Version
Vasculitis Module
Created by Dr. Arthur Bankhurst
Objectives for presentation and differential diagnosis of vasculitis:
1. To learn the spectrum of vasculitis. Certain vasculitides tend to involve certain size
blood vessels.
2. To learn how the presentation can alert one to a diagnosis of vasculitis (and type of
vasculitis).
3. To learn what non-vasculitic disease can mimic vasculitis.
4. To prove the diagnosis of vasculitis.
5. To learn some of the criteria for the diagnosis of specific types of vasculitis.
References:
1. Small Vessel Vasculitis, Jennette. J, et al, NEJM 337, 1512-1523 (1997)
2. The Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis, Jeo. P, et al, Am J
Med, 117, 39-50 (2004)
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Case Presentation:
A 32 year old woman comes in to the urgent care clinic on a Friday morning with an intermittent
skin rash over the legs for 2 months. Lesions are not painful and resolve with minimal
discoloration. PMH is positive for chronic sinusitis requiring intermittent antibiotics. ROS is
negative except for a 15 pound weight loss x 2 months.




Objective Findings
o Non-ulcerating purpura over the lower extremities, otherwise non-remarkable.
Action
o You order a chest x-ray, CBC, urinalysis, ESR and metabolic panel and schedule
a follow for next Tuesday.
Follow up
o You receive the following results in the afternoon:
 Hb 8.9, ESR 115, Creatinine 1.6, UA=20-30 RBC with 3+ protein and no
casts, chest x-ray = multiple infiltrates
What should get done now?
a)
b)
c)
d)
Order an ANA, ANCA, and anti-DNA to be drawn Tuesday?
Admit to the hospital?
Schedule a rheumatology consult for Monday?
Call in prescription for prednisone at 40 mg bid until seen on Tuesday?
Answer: b. Admit to the hospital
This patient has significant organ dysfunction of unknown duration and suspected vasculitis.


Evaluate immediately.
Therapy will depend on obtaining a specific diagnosis. Patients can deteriorate suddenly.
2
Board Questions:
1. A 17 year old woman presents with hypertension, asymmetric BPs, and angina. What are
the studies to be obtained?
i.
ii.
iii.
iv.
ANCA
ANA
ESR, C3, C4
Angiography
Answer: iv. Angiography
Angiography with intravascular pressure of aorta and primary branches. Findings: Left SC
stenosis, right renal artery stenosis, stenosis of coronary arteries.
Diagnosis: Takayasu’s
2. A 51 year old man presents with 3 month history of fever, chills, night sweats and
malaise. New onset palpable purpura on legs. Biopsy showed leukoclastic
(hypersensitivity) vasculitis. Treatment with 60 mg prednisone resulted in improvement.
What would you do next?
i.
ii.
iii.
iv.
v.
Answer:
Add cyclosphosphomide
Add Methotrexate
Add plasmapheresis
Increase corticosteroids
Consider additional diagnoses
v. Consider additional diagnoses
CT of abdomen showed lymphadenopathy, hepatosplenomegaly; subsequent lymph node biopsy
performed.
Diagnosis: Small cell lymphoma
3
Objective I – The Spectrum of Vasculitis
Classification based on the size of predominant blood vessels involved
I. Primary Vasculitides
Predominantly large-vessel vasculitides (aorta, artery, occasionally arterioles)
Takayasu’s arteries
Giant cell arteries
Bechet’s disease
Predominantly medium-vessel vasculitides
Polyarteritis
Cutaneous polyarteritis
Buerger’s disease
Kawasaki’s disease
Primary angitis of the central nervous system
Predominantly small vessel vaculitides *
(arterioles, venules, occasionally veins and arteries)
Goodpasture syndrome
Churg-Strauss syndrome**
Microscopic polyangitis**
Wegener’s granulomatosis**
Cutaneous leukocytoclastic vasculitis (hypersensitivity vasculitis)
Henoch – Schonlein purpura
Essential cryoglobulinemia
Hypocomplementemic urticarial vasculitis
Renal – limited or pulmonary-renal vasculitis**
II. Secondary Forms of Vasculitis
Connective Tissue disease (RA, SLE, Sjogren’s, Inflammmatory Myopathic)
Inflammatory bowel disease
Paraneoplastic
Infection
Drug-induced vasculitis
* Small vessel vasculitis is defined as a vasculitis that affects vessels smaller than arteries,
such as arterioles, venules, and capillaries. It is important to note that small vessel vasculitis
sometimes affects arteries and the vascular distribution overlaps that of the medium-sized
and large vessel vasculitis.
** Associated with ANCA.
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Objective 2 – The Feature on Presentation Which Should Alert One to the Possibility of
Vasculitis
Typical Clinical Manifestations of Large, Medium, and Small Vessel Involvement *
Large -
Limb claudication
Asymmetric blood pressure
Absence of pulses
Bruits
Aortic dilatation
Medium -
Cutaneous nodules
Ulcers
Livedo reticularis
Digital gangrene
Mononeuritis multiplex
Microaneurysms
Small -
Purpura
Vesiculobullous lesions
Glomerulonephritis
Alveolar hemorrhage
Cutaneous extravascular necrotizing granulomas
Splinter hemorrhages
Uveitis/episcleritis/scleritis
Common
to all
Fever
Weight loss
Malaise
Arthralgias and arthritis
* Remember – features that greatly enhance the possibility of vasculitis: glomerulonephritis,
palpable purpura, peripheral neuropathy, ischemia in young patients (claudication, MI, TIA,
hypertension), heart murmur, history of high risk sex activity, history of prominent liver
abnormalities.
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Objective 3 – What diseases can mimic vasculitis?





Sepsis (bacterial endocarditis, HIV, viral hepatitis)
Drug toxicity (Ergots, cocaine, amphetamines, others *)
Paraneoplastic syndromes
Atrial myxoma
Cholesterol emboli syndromes
* Not only mimics but can cause secondary vasculitis!
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Objective 4 – To prove the diagnosis of vasculitis
I. Laboratory tests that are helpful in the diagnosis of vasculitis



Tests suggesting immune complex formation and/or deposition
o RF and cryoglobulins
o ANA
o Low C3 or C4 levels
Tests suggesting necrotizing vasculitis without immunocomplex formation
o ANCA
Test suggesting systemic inflammation
o ESR
o CRF
ANCA
 ANCA by immunofluoresence
o C-ANCA – Wegeners (60-90%)
o P-ANCA – Microscopic polyangitis (50-80%)
 Ulcerative colitis (40-80%)
 Crohn’s (10-40%)
 ANCA cytoplasmic antibodies
o Proteinase 3 (PR3) = Wegener’s
o Myeloperoxidose (MPA) – microscopic polyangitis
o Other non-specific or not identified P-ANCA
II. Considerations on the diagnosis and classification of systemic vasculitis

Size of blood vessel

Epidemiologic features (age, sex, ethnic background)
o Giant cell arteritis: Age>50, female 3:1, Northern European
o Takayasu’s: Age<40, female 9:1, Asian
o Behcet’s: Silk route countries
o Polyarteritis: Males>females
o Kawasaki’s: Children from Asian ancestry
o Wegener’s: Caucasians>blacks
o H-S purpura: Only 10% adults, 90% children

Pattern of organ involvement
o Wegener’s: Kidney, upper airway, lung
o H-S purpura: Kidney, GI tract, skin
7

Pathologic features
o Granulomatous inflammation: giant cell, Takayasu, Wegener’s, Churg-Strauss,
primary CNS
o Pauci-immune versus IC deposition:
 Wegener’s, MPA, CS (many are ANCA+) versus Goodpasture’s, HS,
cryoglobulinemia, Bechet’s, hypersensitivity, secondary vasculitis
o Infection Association: HBV with PN, HCV with Cryoglobulins
III. Role of Biopsy in Diagnosis
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
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If biopsy impractical (large vessel, abdominal, etc) Angiograph (better than MRA)
Asymptomatic site – low yield (>20%)
Symptomatic or abnormal sites (>65%)
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Objective 5 – To learn the criteria for the diagnosis of systemic vasculitis
Names and Definitions of Vasculitis from the Chapel Hill Consensus Conference
I. Large-Vessel Vasculitis
Giant-cell (temporal) Granulomatous arteritis of the aorta and its major branches,
arteries
with a predilection for the extacranial branches of the carotid
artery. Often involves the temporal artery. Usually occurs in
patients more than 50 year old and is often associated with
polymyalgia rheumatica.
Takayasu’s arteritis
Granulomatous inflammation of the aorta and its major branches.
Usually occurs in patients younger than 50.
II. Medium-sized Vessel Vasculitis
Polyarteritis nodosa
Kawasaki’s disease
Necrotizing inflammation of medium-sized or small arteries
without glomerulonephritis or vasculitis in arterioles, capillaries, or
venules.
Arteritis involving large, medium-sized, and small arteries and
associated with mucocutaneous lymph node syndrome. Coronary
arteries are often involved. Aorta and veins may be involved.
Usually occurs in children.
III. Small Vessel Vasculitis
Wegener’s
Granulomatosis†
Granulomatous inflammation involving the respiratory tract
and necrotizing vasculitis affecting small-to-medium-sized vessels
(e.g., capillaries, venules, arterioles, and arteries). Necrotizing
glomerulonephritis is common.
Churg-Strauss syndrome†
Eosinophil-rich and granulomatous inflammation involving the
respiratory tract and necrotizing vasculitis affecting small to
medium-sized vessels and associated with asthma and eosinophilia.
Microscopic polyangiitis†
Necrotizing vasculitis with few or no immune deposits affecting
small vessels (capillaries, venules, or arterioles). Necrotizing
arteritis involving small and medium-sized arteries may be
present. Necrotizing glomerulonephritis is very common.
Pulmonary capillaritis often occurs.
Henoch-Schönlein
Vasculitis with IgA-dominate immune deposits affecting
Purpura:
small vessels (capillaries, venules, or arterioles). Typically
involves skin, gut, and glomeruli and is associated with arthralgias
or arthritis.
Essential Cryoglobulinemic Vasculitis with cryoglobulin immune deposits affecting Angiitis:
small vessels (capillaries, venules, or arterioles) and
associated with cryoglobulins in serum. Skin and glomeruli are
often involved.
†These vasculitides are associated with antineutrophil cytoplasmic auto-antibodies (ANCA).
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Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to Dr.
Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient curriculum
in general:
6) Please circle one:
Attending
Resident (R2/R3)
Intern
10
Medical student