Systemic Vasculitis:

a clinical approach

Geordie Lawry MD
Chief, Rheumatology
UC IRVINE

Medicine HS Noon Conference: October 2015

 Objectives 1
List the 4 clinical features which should
prompt you to CONSIDER A
DIAGNOSIS of systemic vasculitis
List the Big 5 essential questions in
patients with SUSPECTED GIANT
CELL ARTERITIS
Describe what is meant by
PULMONARY RENAL SYNDROME
 Objectives 2
List at least 3 ORGANS / SITES commonly
involved in:

CRYOGLOBULINEMIC VASCULITIS
GRANULOMATOUS POLYANGIITIS (GPA)
MICROSCOPIC POLYANGIITIS (MPA)
CLASSIC POLYARTERITIS NODOSA
GIANT CELL ARTERITIS
 Objectives 3
List at least 2 ANCA VASCULITIS
SYNDROMES, associated ANCA
pattern / target antigens
List at least 2 vasculitides which are
NOT ASSOCIATED WITH ANCA
List at least 3 or more conditions that
can MIMIC THE CLINICAL
FEATURES OF VASCULITIS
 VASCULITIS: Talk Outline
Introduction and Definitions
Approach to vasculitis
Specific Disorders:
Giant Cell Arteritis
Granulomatous polyangiitis (Wegeners)
Microscopic Polyangiitis
Polyarteritis Nodosa
Cryoglobulinemia
Take Home
VASCULITIS: principles 1
group of clinical syndromes
characterized by inflammation
of blood vessels

Artery: WBC
Normal Artery
inflammation in wall
 VASCULITIS: principles 2

systemic diseases that can affect many

different organ systems

can be difficult to diagnose: challenging

clinical picture even for experienced
clinicians

can be life-threatening
VASCULITIS: classification

www.wegenersgranulomatosis.net/imageRJN.JPG
General Approach to
Vasculitis

Throw up your hands.

General Approach to
Vasculitis

Slap at it .
 When should vasculitis be
suspected? 1
MULTISYSTEM inflammatory disease
Significant CONSTITUTIONAL SYMPTOMS
RAPIDLY PROGRESSIVE organ
dysfunction
HIGH ESR
SEVERE anemia
PLATELETS > 500K
 When should vasculitis be
suspected? 2
CLINICAL FEATURES PARTICULARLY
SUGGESTIVE of small vessel
inflammation:
SKIN: palpable purpura *
LUNGS: pulmonary infiltrates /
hemoptysis
KIDNEY: active urinary sediment
NEURO: foot drop **
What is the approach to
a patient suspected of
having vasculitis?

WHAT IS YOUR
APPROACH TO ANY
COMPLEX MEDICAL
PROBLEM?
 General Approach to
Vasculitis

Gather your equipment.

Find the target.
Take aim..
NAIL IT !
COMPLEX MEDICAL PROBLEMS 1

HISTORY: PATIENTS STORY

get careful CHRONOLOGY
.PROBLEMS

PHYSICAL EXAM: BODYS STORY

thoughtful, thorough
..MORE PROBLEMS

LABORATORY: BEHIND-THE-SCENES STORY

Basic CBC, CHEMS, LFTs, UA/micro, CXR
..MORE PROBLEMS

.
COMPLEX MEDICAL PROBLEMS 2

Develop a strategy: PROBLEM LIST

CREATE PROBLEM LIST

LIST EVERYTHING [split dont lump]

PRIORITIZE PROBLEM LIST

WHATS THE BIG GORILLA(S) HERE?

WORK the PROBLEM LIST

COMPLEX MEDICAL PROBLEMS 3

WORK the PROBLEM LIST

Think of 3 explanations for each problem

Create a differential diagnosis

What are the major organs involved?

Do they inter-relate?
Do the patients, bodys and the behind-the-
scenes stories fit together in some way?
COMPLEX MEDICAL PROBLEMS 4

SYSTEMIC VASCULITIS ?

Are there additional tests which could

help confirm this suspicion?

Serologic tests
Imaging studies
Tissue biopsy
VASCULITIS: additional testing 1

Serologic tests
ANCA
Hepatitis B surface antigen
Hepatitis C, C3 & C4
HIV
ANA
ACA, lupus anticoag panel
VASCULITIS: additional testing 2

Imaging studies
Sinus CT scan
Chest CT scan
Mesenteric
angiogram
VASCULITIS: additional testing 3

Tissue biopsy
Temporal artery
Sural nerve
Muscle
Lung
Renal
 Common Clinical
Manifestations
Systemic Respiratory
Fever, sweats, Sinusitis / Epistaxis
weight loss Pulmonary infiltrates
Skin
Palpable Purpura Gastrointestinal
Neurologic Abdominal Pain
Mononeuritis Multiplex Bloody stools
Musculoskeletal Renal
Arthralgia / arthritis Glomerulonephritis
Muscle pain / Hypertension
claudication
 CUTANEOUS

Palpable Purpura
Livedo Reticularis
Splinter Hemorrhages
 NEUROLOGIC
Mononeuritis multiplex:
check for FOOT DROP

Sural nerve biopsy showing vasculitis

 RESPIRATORY: upper
Sinusitis
Or

www.conseils-orl.com/.../sommaire_epistaxis.htm
 RESPIRATORY: lower
Pulmonary infiltrates
Nodules
Cavities
 GENITOURINARY
Glomerulonephritis
Hypertension
Hematuria
RBC casts

Testicular pain
(especially PAN)

www.bio.davidson.edu/.../Cresgn.jpg
 MUSCULOSKELETAL
Polyarthralgias - common
Polyarthritis - less common

Myalgias - common
Myositis - biopsy may demonstrate
vasculitis in muscle
 GASTROINTESTINAL
Mesenteric ischemia
pain 30 minutes after eating
bloody diarrhea
bowel perforation
hepatitis
pancreatitis
cholecystitis

library.med.utah.edu/WebPath/COW/COW125.html
 OCULAR
Scleritis
Retinal Vasculitis

Iritis

http://www.uveitis.org/images/sa
rcoid6.jpg

eyelearn.med.utoronto.ca/.../RedE
ye/10Sclera.htm http://webmedia.unmc.edu/eye/iritis.jpg
Common Laboratory Findings
INFLAMMATION:

Elevated ESR (can be > 100)

Elevated CRP
Leukocytosis
Thrombocytosis
Anemia
Low Albumin
 VASCULITIS MIMICS
INFECTIOUS DISEASES
Endocarditis
HIV
DRUGS
Cocaine
Methamphetamine
CHOLESTEROL EMBOLI
ANTIPHOSPHOLIPID ANTIBODY SYNDROME
 Questions?
In the ACR diagnostic criteria for Giant Cell
Arteritis (Temporal Arteritis), a patient needs
to be greater than what age?
A. > 40 years
B. > 50 years
C. > 60 years
D. > 70 years
E. > 80 years
 Questions?
In the ACR diagnostic criteria for Giant Cell
Arteritis (Temporal Arteritis), a patient needs
to be greater than what age?
A. > 40 years
B. > 50 years
-Almost all are > 60
C. > 60 years
-Average age is 70
D. > 70 years
E. > 80 years
Specific Entities

www.wegenersgranulomatosis.net/imageRJN.JPG
 Giant Cell Arteritis
ACR Criteria (3 of 5)

Age > 50
New onset headache
ESR (Westergren) 50
Abnormal artery biopsy
(mononuclear cell infiltrate,
granulomatous inflammation,
usually multinucleated giant cells)
Temporal artery
abnormality (tender or
decreased pulse)

Arthritis Rheum. 1990;33:1122.

 Giant Cell Arteritis
(Other clinical manifestations)
Visual loss, jaw/tongue claudication, scalp
tenderness
Fever, weight loss
PMR symptoms (proximal muscle pain)
10% with large vessel involvement (e.g.
subclavian artery)
Blindness (ischemic optic neuropathy) is
major complication to avoid
 GCA:Biopsy
Temporal artery biopsy
large specimen (4-6 cm)
multiple sections evaluated
Infiltration of vessel wall with
WBC
Granulomata, Giant Cells
Necrotic material
 GCA: Therapy
Corticosteroids mainstay of therapy
(~1 mg/kg)
Calcium and vitamin D
Consider bisphosphonates
Try to prevent visual loss with therapy:
Treat, then biopsy!
 Questions?
The confirmatory antibody for a positive C-
ANCA in a patient suspected of having
Wegeners Granulomatosus is:
A. Topoisomerase
B. Histidine tRNA synthetase
C. Smith
D. Proteinase-3
E. Myeloperoxidase
 Questions?
The confirmatory antibody for a positive C-
ANCA in a patient suspected of having
Wegeners Granulomatosus is:
A. Topoisomerase
B. Histidine tRNA synthetase
C. Smith (Sm)
D. Proteinase-3 C is the 3rd letter
E. Myeloperoxidase of the alphabet:
Pr-3 C-ANCA
 Granulomatous Polyangiitis
(GPA) formerly Wegeners
Necrotizing vasculitis that affects the small
vessels of the respiratory tract and renal
system: PULMONARY-RENAL SYNDROME
Age ~ 40s: M > F 2:1
 Granulomatous Polyangiitis (GPA)
ACR Criteria (3 of 5)

Nasal or oral inflammation (oral ulcers or bloody nasal

drainage)
Abnormal chest radiograph (nodules, fixed infiltrates,
cavities)
Urinary sediment (> 5 RBC/ hpf or casts)
Abnormal Biopsy: showing vasculitis
Proteinase-3 antibodies

Arthritis Rheum 1990;33:1101.

 Granulomatous Polyangiitis
(GPA) : Respiratory Involvement
Sinusitis
Nasal septal ulceration
Pneumonitis
few symptoms until late
usually no mediastinal
lymphadenopathy
nodules that can
cavitate
 Granulomatous Polyangiitis
(GPA) : Renal Involvement
85% of patients
Focal/segmental
necrotizing
glomerulonephritis
Usually progressive

www.bio.davidson.edu/.../Cresgn.jpg
 Granulomatous Polyangiitis
(GPA) : ANCA
AntiNeutrophil Cytoplasmic Antibody
C (cytoplasmic staining) ANCA
Proteinase 3 (C is the 3rd letter)
Pulmonary-renal disease
sensitivity of 95%
specificity of 95%
Limited disease
lower sensitivity and specificity
 Granulomatous Polyangiitis (GPA):
Tissue Biopsy
Yield of biopsy
Lung
Open highest yield
Bronchoscopy - lower yield
Sinus - 40% yield
Renal
Vasculitis rarely seen
Focal proliferative GN is the typical finding
 Granulomatous Polyangiitis
(GPA) : Rx
Prior to cyclophosphamide, 80-90% mortality
With cyclophosphamide, 5-10% mortality
Concern about long-term toxicity of PO
cyclophosphamide (bladder especially)
IV CYTOXAN no significant bladder risk
Rituximab: very effective for induction &
maintenance
Azathioprine for maintenance
 Microscopic Polyangiitis
(MPA)
Systemic vasculitis with predominant
small vessel involvement
Separate disease from PAN (Initially thought to
be a variant of PAN)

Usually RPGN and sometimes with

pulmonary hemorrhage
More common than PAN (both are rare)
 MPA: Clinical Manifestations
Renal manifestations 79%
Weight loss 73%
Skin involvement 62%
Mononeuritis multiplex 58%
Fever 55%
Arthralgias/Myalgias 50%
Pulmonary involvement 25%
 MPA: ANCA
P (perinuclear) ANCA
Myeloperoxidase antibodies
Sensitivity/Specificity
unclear
 MPA: Epidemiology & Rx
Ave. age 57
Males > Females (slightly)

Cyclophosphamide decreases mortality

IV CYTOXAN no significant bladder risk
Rituximab: very effective for induction &
maintenance
Azathioprine for maintenance
 Polyarteritis Nodosa
Necrotizing vasculitis of medium & small arteries
Age ~ 40s; M > F
Constitutional symptoms are common
fever 50%
weight loss 50%
Vasculitis can be variable in distribution making
diagnosis difficult
 Polyarteritis Nodosa
ACR Criteria (3 of 10)

Wt loss > 4 kg Diastolic BP > 90

Livedo reticularis BUN or Creatinine
Testicular pain Hepatitis B virus
Myalgias, weakness or Arteriographic
leg tenderness abnormality
Mononeuropathy or Biopsy of small or
polyneuropathy medium artery
containing PAN

Arthritis Rheum. 1990;33:1088

 Classic PAN: Manifestations
Mononeuritis multiplex 50%
Renal involvement: 60%
(renal arteries, interlobular arteries)
Hypertension (more common)
Glomerulonephritis (uncommon)
Abdominal involvement 45%
Arthralgias/Myalgias/Myositis 64%
Testicular pain 25%
Pulmonary involvement rare
 Polyarteritis Nodosa

Association with
Hepatitis B (surface
antigen)
ANCA
Classic PAN
is NOT associated with
ANCA
 Cryoglobulinemia 1
Paradigm of small vessel vasculitis
Association with hepatitis C infection
Damage is immune complex-mediated
Cryoprecipitate Hepatitis C Ag Ab
Complement fixing: C4 consumption
C4 levels VERY low
Cryoglobulinemia 2
 Cryoglobulinemia 3
PATTERN OF ORGAN INVOLVEMENT:
constitutional
Cutaneous
articular
vascular
neurologic
 Cryoglobulinemia 4
PATTERN OF LABORATORY FINDINGS:
rheumatoid factor
complement C4
cryoglobulin (cryocrit)

TREATMENT:
Antiviral therapy . clearance of hep C virus!
VASCULITIS: classification

www.wegenersgranulomatosis.net/imageRJN.JPG
VASCULITIS OF SMALL >> MEDIUM-SIZED
VESSELS:

drug-induced small vessel vasculitis

(hypersensitivity vasculitis),
Henoch-Schnlein purpura (IgA vasculitis),
ANCA-associated vasculitis
(granulomatosis with polyangiitis [Wegeners],
microscopic polyangiitis, eosinophilic granulomatosis
with polyangiitis [Churg Strauss syndrome]),
infection-related vasculitis
(bacterial endocarditis, poststreptococcal vasculitis and
glomerulonephritis) plus hepatitis C-related
cryoglobulinemia)
 vasculitis associated with CTD
(SLE, RA, Sjgren's)

VASCULITIS OF MEDIUM-SIZED VESSELS:

classic polyarteritis nodosa (PAN)

VASCULITIS OF LARGE VESSELS:

Giant cell arteritis
Takayasu arteritis

MIMICS OF VASCULITIS:
infectious, thrombotic, and embolic disorders