VASCULITIS

George R. Mount, CPT USA MC

Rheumatology Fellow
Walter Reed AMC

Goals

Overview
Clinical patterns
Diagnostic aids
Treatment paradigms
Cases and questions

Introduction

Inflammation and necrosis of blood

vessels
Occlusion and ischemia
Immunologic mechanisms
Multi-system disease with
constitutional symptoms and
inflammatory laboratory indices

Vasculitis: Primary or
Secondary?

Primary: Vasculitis is the principal

feature of the disease

Secondary: Vasculitis is a
complication of another disease or
toxin (e.g. RA, infection, malignancy)

Classification of Vasculitis

No universally accepted
classification system

Vessel size
Histopathology
Dominant organ involvement

Overlap

Classification of Vasculitis

Large Vessel
Giant cell arteritis
Takayasus

Medium Vessel
Polyarteritis Nodosa
Kawasakis

Small Vessel
Wegeners, Microscopic polyangitis,
Henoch-Scholein purpura, Cryoglobulemic,
hypersensitivity

Classification of Vasculitis

www.rheumtext.com Hochberg et al (eds)

When to Suspect a Vasculitis

Unexplained ischemia:
Claudication, limb ischemia, angina,
TIA, stroke, mesenteric ischemia,
cutaneous ischemia
Especially in a young individual

Multiorgan dysfunction:
Systemically ill patient
Other suggestive features

When to Suspect a Vasculitis

Other suggestive features:

Glomerulonephritis
Palpable purpura
Peripheral neuropathy
Established autoimmune disease

When to Suspect a Vasculitis

Systemic illness must exclude

alternative diagnoses:

Sepsis
Drug toxicity
Malignancy
Coagulopathy

General Approach to
Diagnosis
Attempt to exclude other
processes
Consider the age, gender,
ethnicity of the patient
Determine which organ systems
are involved
Estimate the size of the vessels
involved

Demographic Associations

Clues to Diagnosis

Clues to Diagnosis

Clues to Diagnosis

Clues to Diagnosis

Clues to Diagnosis

Approach to Diagnosis: Labs

Determine organ involvement

Exclude other diseases
Routine labs: CBC, BMP, UA, ESR, CRP,
LFTs
Infection w/u: cultures, viral serologies
(HBV, HCV, HIV)
Autoimmune serologies: ANA, RF,
ANCAs, ENA, ds DNA, C3/C4
Misc: CK, anti-GBM, SPEP, Cryoglobulins

Approach to Diagnosis:
ANCAs 101

Antibodies directed against neutrophil

granule constituents
c-ANCA

Stains cytoplasm (hence c)

Main target antigen: proteinase-3
Highly specific (>90%) for Wegeners

p-ANCA

Stains perinuclear (hence p)

Main target antigen: myeloperoxidase
A/w MPA and Churg-Strauss

Approach to Diagnosis:
Biopsy

Blind biopsy generally low yield

Less than 20%

Go where the money is.

Approx. 66% success in symptomatic organs
Examples: Temporal artery biopsy, kidney
biopsy, sural nerve biopsy, testicular biopsy

Vasculitic lesions tend to be focal and

segmental

Approach to Diagnosis:
Angiogram

If biopsy is impractical
Important in large vessel vasculitis
Patient with abdominal pain
Renal or mesenteric vasculitis

Approach to Diagnosis:
Angiogram

Prognosis

Untreated is a rapidly progressive,

usually fatal, disease
The prognosis is determined by the
extent and number of organs
involved
Morbidity and mortality can be
prevented if recognized and treated
early

Treatment

Determined by:
Type and severity of organ involvement
Rate of disease progression

Corticosteroids
Usually 1mg/kg initially
Pulse dose corticosteroids

Immunosuppressive therapy
Cytoxan, Methotrexate, Imuran

Case

A previously healthy 22yo male college

student had an URI 2 weeks ago, RX with
PCN
He develops abdominal pain, bilateral ankle
pain & swelling with raised purpuric lesions
over lower extremities
Labs:
creatinine 3.0 mg/dL, BUN 46 mg/dL
Urinalysis: 4+ proteinuria, 2+ RBCs, sev. RBC
casts/ hpf

Case

Case

What is the most likely cause of renal

disease in this patient:
A. Lupus nephritis
B. Acute post-streptococcal
glomerulonephritis
C. Henoch-Schonlein purpura
D. Allergic interstitial nephritis
E. Goodpastures syndrome

Case

What is the most likely cause of renal

disease in this patient:
A. Lupus nephritis
B. Acute post-streptococcal
glomerulonephritis
C. Henoch-Schonlein purpura
D. Allergic interstitial nephritis
E. Goodpastures syndrome

Henoch-Schonlein Purpura

Small vessels, post capillary venules

Palpable purpura, arthralgias, abdominal
pain, renal disease
Males=females
Mean age 5 yrs.
Preceding URI in 2/3 (1-3 weeks)
Tissue deposition of IgA-containing
immune complexes (skin, kidneys, bowel)

Henoch-Schonlein Purpura

GI involvement in 85%
Severe cramping, pain, nausea,
vomiting, bleeding
Major hemorrage or intussuseption
is an uncommon but life-threatening
complication in children

Henoch-Schonlein Purpura

Renal involvement (10-50%)

Renal disease more severe in adults

Determines prognosis
Many recover with no therapy
Asymptomatic hematuria
proteinuria & renal insufficiency
(cresentic GN)
< 0.5% progress to ESRD

Henoch-Schonlein Purpura

Uncommon

Testicular involvement
Pulmonary hemorrhage
CNS complications

Henoch-Schonlein Purpura

Usually single episodes < 4 weeks

duration
40% recurrence rate after period of
wellness

Treatment
Supportive measures
Corticosteroids for GI vasculitis and
hemorrhage
? CS early in nephritis

Case

50yo woman presents with 1 week of fever,

chills, chest pain, cough, dyspnea and
paresthesias in LE

PMHx: bronchial asthma (7 yrs), allergic

rhinitis
PE: 100 F, HR 98, BP 120/70, RR 16/min

wheezes/ rhonchi bilaterally

mild peripheral weakness in LE
sensory dysesthesia in stocking distribution
bilaterally

Case

Lab: WBC 12.8 (N 30%, L 25%, Eos

40%)
Blood/sputum cultures: negative
ANA neg, p-ANCA + 1:20
CXR: patchy bilateral infiltrates

Case

Case
She is treated with empiric antibiotics over 3
days with no improvement in symptoms.
What is the most likely diagnosis:
A. Eosinophilic bronchitis
B. Idiopathic hypereosinophilic syndromes
C. Churg-Strauss syndrome
D. Wegeners granulomatosis
E. Polyarteritis nodosa

Case
She is treated with empiric antibiotics over 3
days with no improvement in symptoms.
What is the most likely diagnosis:
A. Eosinophilic bronchitis
B. Idiopathic hypereosinophilic syndromes
C. Churg-Strauss syndrome
D. Wegeners granulomatosis
E. Polyarteritis nodosa

Churg-Strauss Vasculitis

Necrotizing, granulomatous vasculitis of

small arteries and venules

Prior asthma

Started on leukotriene inhibitors

and weaned off steroids
Allergic rhinitis
Eosinophilia
Pulmonary infiltrates
Intra/extravascular granulomas

Churg-Strauss: Criteria- 4/6

Asthma
Eosinophilia (>10%)
Mono/ Polyneuropathy
Pulmonary Infiltrates Non-fixed
Paranasal sinus abnormality
Extravascular eosinophils

Churg-Strauss Vasculitis

Asthma precedes vasculitis

Confusion with Wegeners
Nasal/sinus DZ is NON-destructive
Pulmonary nodules less common

Churg-Strauss Vasculitis

p-ANCA (MPO): 70%

More responsive to steroids alone

Case

A 65yo woman c/o 6 months of malaise, 9lb

weight loss, recurrent sinusitis, and a
persistent cough. On exam, she is afebrile, the
mid-portion of the nasal bridge has a flattened
appearance, and both sides of the nasal
septum are ulcerated. RF is positive and ESR is
66.
Which of the following tests would be most
helpful in determining the diagnosis:
A. Nasal septum biopsy
B. Chest radiograph
C. Measurement of ANCA antibodies
D. Sputum culture
E. Measurement of anti-GBM antibodies

Case

A 65yo woman c/o 6 months of malaise, 9lb

weight loss, recurrent sinusitis, and a
persistent cough. On exam, she is afebrile, the
mid-portion of the nasal bridge has a flattened
appearance, and both sides of the nasal
septum are ulcerated. RF is positive and ESR is
66.
Which of the following tests would be most
helpful in determining the diagnosis:
A. Nasal septum biopsy
B. Chest radiograph
C. Measurement of ANCA antibodies
D. Sputum culture
E. Measurement of anti-GBM antibodies

Wegeners Granulomatosis

Necrotizing, granulomatous vasculitis

small vessels
Affects persons of any age
No significant sex predilection
Upper and lower respiratory tracts
Glomerulonephritis
Frequently vasculitis of other organs

Wegeners Granulomatosis

Nasal/ sinus disease destructive

Renal follows respiratory
May progress rapidly

Non-specific abnormalities

Conjunctivitis, scleritis, episcleritis

Proptosis (15%)

Wegeners Granulomatosis

Criteria: 2 or more
Nasal/oral ulcers OR purulent/
bloody discharge
Abnormal CXR - nodules, focal
infiltrates, cavities
Abnormal urine sediment
(microhematuria, RBC casts)
Granulomatous inflammation

Wegeners Granulomatosis

c-ANCA

> 90% + in patients with classic symptoms

Facilitates clinical DX
Does not eliminate need for BX
Not for intensification of therapy

Open biopsy
Paranasal, nasal, larynx, lung
Renal biopsy rarely distinctive enough to
be definitive

Wegeners Granulomatosis

Outcomes:

Intervention

Survival

None

50% at 5 months

Glucocorticoids

50% at 1 year

GCS + Cytoxan

80% at 8 years

Distinguishing CSV & WG

CSV

WG

Asthma

+++

uncommon

Eosinophils

+++

occ /modest

Atopy

+++

uncommon

Upp airway destruction

uncommon

Pulmonary nodules

occasional

++

Renal failure

++

Case

A 29yo woman presents with a 4yr h/o skin ulcers on

her lower extremities. A previous punch biopsy
showed thrombotic lesions in small blood vessels of
the dermis. Treatment has mostly focused on wound
care. On exam the ulcers are noted, as is livedo
reticularis, a decreased right hand grip, and a right
foot drop.
Which of the following is the most likely diagnosis:
A. Lymphoma, with a paraneoplastic syndrome
B. Takayasus arteritis
C. Systemic lupus erythematosus
D. Polyarteritis nodosa
E. Kawasakis disease

Case

A 29yo woman presents with a 4yr h/o skin ulcers on

her lower extremities. A previous punch biopsy
showed thrombotic lesions in small blood vessels of
the dermis. Treatment has mostly focused on wound
care. On exam the ulcers are noted, as is livedo
reticularis, a decreased right hand grip, and a right
foot drop.
Which of the following is the most likely diagnosis:
A. Lymphoma, with a paraneoplastic syndrome
B. Takayasus arteritis
C. Systemic lupus erythematosus
D. Polyarteritis nodosa
E. Kawasakis disease

Polyarteritis Nodosa

Primary systemic necrotizing

vasculitis

Small/ medium sized arteries

Very rarely veins
Never large elastic arteries
May be a manifestation of other disease

RA, Sjogrens, Hepatitis B or C

Limited progressive/ fulminant

Polyarteritis Nodosa

Any age
Peak years: 30-60
M:F Ratio 2:1

Polyarteritis Nodosa

Fever, malaise, weight loss

Arthritis/ arthralgia (50%)
Skin lesions
Neurologic (Peripheral > central) (50-70%)
Renal (70%)
HTN (25%)
Cardiac (50%)
GI (50%)
Classic PAN- Rare lung disease

Polyarteritis Nodosa

Anemia, leukocytosis, thrombocytosis

ESR elevation
Hypocomplementemia (25%)
Hepatitis B SAg (10-54%)
Hep C Ab: 5%
p-ANCA (MPO): < 10%, c-ANCA is rare

PAN-Diagnosis

Biopsy Symptomatic sites

Skin, Sural nerve, Muscle, Liver, Testes,
Temporal Artery
Renal- does not allow differentiation of
type of vasculitis (segmental necrotizing
GN)

ANGIO - ABDOMINAL VISCERA

Evidence of intra-abdominal involvement
Other involved organs not available for bx

PAN- Prognosis &Treatment

Untreated - 85% mortality at 5

years
Treatment - 80% survival at 5
years
Corticosteroids
Cytotoxics

40% relapse (median 33 months)

Case

A 32yo Korean woman presents with a 30lb

weight loss, low-grade fevers and arthralgias.
She notes back pain between her shoulder
blades. She notes pain in her arms with any
prolonged activity. Recent labs are notable for a
platelet count of 800K and an ESR of 130. On
exam, her HR is 100bpm and her BP is 60/40 in
both arms.
What is the next step in her management:

A.
B.
C.
D.
E.

Hospitalize for further evaluation

Order blood cultures, get an ANA and RF
Perform a careful exam, listen for subclavian bruits
Administer IV saline
Advise the patient to begin Fe supplementation

Case

A 32yo Korean woman presents with a 30lb

weight loss, low-grade fevers and arthralgias.
She notes back pain between her shoulder
blades. She notes pain in her arms with any
prolonged activity. Recent labs are notable for a
platelet count of 800K and an ESR of 130. On
exam, her HR is 100bpm and her BP is 60/40 in
both arms.
What is the next step in her management:

A.
B.
C.
D.
E.

Hospitalize for further evaluation

Order blood cultures, get an ANA and RF
Perform a careful exam, listen for subclavian bruits
Administer IV saline
Advise the patient to begin Fe supplementation

Takayasus Arteritis

Large vessel
Unknown etiology
Aorta/branches
Pulseless Disease

Takayasus Arteritis

Women in reproductive years

10X more than men
Asia, Eastern Europe, Latin America

Granulomatous Panarteritis

Takayasus Arteritis

98% have stenotic lesions, 27%

aneurysms
Subclavian & aortic arch most
common, 93%
40- 80% renal artery stenosis

Takayasus Arteritis

Arterial stenoses/organ ischemia

Claudication
Transient cerebral ischemia/ stroke
Renal artery hypertension
CHF
Angina
MI
Mesenteric vascular insufficiency

Takayasus Arteritis

In the absence of complications

(retinopathy, HTN, aortic v. insuff),
15 yr survival 95%
Most respond to steroids alone
40% will need cytotoxics

Case

A 78yo woman c/o headache for the

past 8 days and notes the onset of
double vision and blurring, lasting
15min before resolving. She has lost
15lb over the past 2 months.
Which is the best next step in her
management:

A.
B.
C.
D.
E.

Refer her to an ophthalmologist or neuro

Schedule a temporal artery biopsy
Test her ESR and schedule a TA biopsy
Administer sumitriptan
Administer prednisone, 60mg,
immediately and schedule a TA biopsy

Case

A 78yo woman c/o headache for the

past 8 days and notes the onset of
double vision and blurring, lasting
15min before resolving. She has lost
15lb over the past 2 months.
Which is the best next step in her
management:

A.
B.
C.
D.
E.

Refer her to an ophthalmologist or neuro

Schedule a temporal artery biopsy
Test her ESR and schedule a TA biopsy
Administer sumitriptan
Administer prednisone, 60mg,
immediately and schedule a TA biopsy

Giant Cell Arteritis

Temporal arteritis & Cranial arteritis

Large vessel, granulomatous arteritis
Extracranial vessels (arteries) >>>
intracranial
Aortic arch vessels (10-15%)
Unknown etiology
Persons over age 50 (mean 70)
2-3x more common in women

Giant Cell Arteritis

Segmental vessel inflammation

Multinucleate giant cell, lymphocytic
predominancePMNs rare
Thrombosis
Giant cells not required for diagnosis

Giant Cell Arteritis

Nonspecific constitutional symptoms- fever,malaise,

fatigue
Headache (> 2/3)
Scalp tenderness +/- nodules
Temporal artery tenderness
Visual symptoms (blindness 15%)
Intermittent claudication (jaw, tongue, extremities)
Neuropathies/TIA/Stroke (30%)
Respiratory Tract (10%)
PMR (40-60%)

Giant Cell Arteritis

Lab

ESR Marked elevation

CRP elevation
Anemia
Thrombocytosis
Increased LAE
Increased Alkaline phosphotase

Giant Cell Arteritis

Biopsy
Vascular involvement not uniform
Length ?: If normal TA exam, obtain 3-5
cm sample and examine at multiple
levels
Negative biopsy
Consider contralateral bx if first bx
normal
When ? ..ASAP

Giant Cell Arteritis

Prednisone 1mg/kg/d
Taper 10%/month after Sx/lab
resolved
Slow taper at 15 mg/d
Lab and Sx
Long term steroids

Steroid sparing with MTX

Giant Cell Arteritis

30% - relapse with steroid taper, esp

prednisone < 20 mg/d
25% - vertebral compression fractures
50% - other serious steroid toxicities,
e.g. HTN, diabetes, CHF, cataracts..

Common Vaculitis Presentations

(aka Board Buzz Words)
Oral & genital ulcers = Behcets
Upper/lower airway disease and
glomerulonephritis = Wegeners

Septal perforation, epistaxis

Recurrent sinus infections

Young female with arm/leg

fatigue and HTN = Takayasus

Common Vaculitis Presentations

(aka Board Buzz Words)
Palpable purpura = small
vessel leukocytoclastic
vasculitis
Hepatitis B = PAN
Hepatitis C = cryoglobulinemia

Questions?