APPROACH TO SYSTEMIC

VASCULITIS
Chingching Foocharoen
Answer the questions
• When do we suspect systemic vasculitis? Clinical syndromes
• What is/are differential diagnosis of vasculitis? Vasculitis mimics
• What are the classical clinical characteristics of vasculitis? Vascular sizes
• How can we make the diagnosis of vasculitis? Investigations
• What are the vasculitis treatments? Treatments

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 When do we suspect vasculitis?
Multi-organ involved Constitutional symptoms

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Large vessels
• Congenital causes
(coarctation, middle
aortic syndrome)
• Hereditary disorders
(Marfan syndrome, Ehler-
Danlos syndrome)
• Atherosclerosis
• Infection: TB, syphilis
• Fibromuscular dysplasia
• IgG4 related disease
Vasculitis mimics
Medium vessels
• Atherosclerosis
• Thromboembolic disease
• Fibromuscular dysplasia
• Vasospastic disorder
• Hypercoagulable state
(APS, TTP)
• Segmental arterial
mediolysis
• Mycotic aneurysm
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Small vessels
• Thromboembolic disease
• Atrial myxoma
• Infectious causes
(endocarditis, HBV, HIV)
• Malignancy (lymphoma,
leukemia)
• Multisystem inflammatory
disorders (sarcoidosis)
• Iatrogenic (post RT)
• IgG4-related disease
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Zarka et al. Int J Rheumatol. 2020;8392542.
 Vasculitis mimics
Pulmonary-renal syndrome
Infectious disease mimics
• Severe bacterial pneumonia
• Postinfectious GN
• Infective endocarditis
• Sepsis with multiorgan failure (ARDS and
AKI)
Cardiac mimics
• Pulmonary edema with cardiorenal AKI
Renal mimics
• Nephrotic syndrome with PE
• Thrombotic thrombocytopenic pupura
Connective tissue diseases
• SLE: LN with ILD (bronchiectasis)
• SSc: ILD with renal crisis
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Asthma and eosinophilia
Infectious diseases
• HIV
• Aspergillosis
Hematologic diseases
• Hypereosinophilic syndrome
• Eosinophilia leukemia
Paraneoplastic syndrome
• Lung cancer
• Hodgkin’s lymphoma
• Non-Hodgkin’s T-cel lymphoma
Pulmonary diseases
• Allergic bronchopulmonary aspergillosis
• Aspirin exacerbated respiratory disease
• Idiopathic eosinophilic pneumonia 6
Zarka et al. Int J Rheumatol. 2020;8392542.
 Vasculitis mimics
Midline destructive lesion
(ENT limited GPA mimics)
Cocaine-induced midline destructive lesions
Necrotizing sinonasal infection
• Bacteria, syphilis
• Mycobacteria
• Fungus
• Parasitic
Neoplastic: NK/T-cell lymphoma
Inflammation
• Sarcoidosis
• IgG4-related disease
Idiopathic midline destructive disease
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Zarka et al. Int J Rheumatol. 2020;8392542.

• Hypertension (renal) • Palpable purpura

• Chest angina pain Vascular size • Arthritis

• Myocarditis, Pericarditis, pleuritic
• Bowel angina pain
• Dyspnea (pulmonary vs) • Interstitial pneumonitis, alveolar
hemorrhage
• Visual loss, blindness
• Polyneuropathy
Medium vessel Small vessel • Glomerulonephritis
• GI bleeding
• Headache, syncope • Scleritis, retinal hemorrhage
• Jaw claudication • Saddle nose, sinusitis, otitis media
• Limb claudication
• Different BP,
hypertension
• Aortic regurgitation
• Livedo reticularis, gangrene,
• Visual loss ulcer, necrosis,
subcutaneous nodule,
• Myalgia, myositis, arthritis
• Myocarditis, arrhythmia
• Hypertension
Large vessel Medium to small vessel • Mononeuritis multiplex
• GI bleeding, ulcer
CF. Khon Kaen University • Retinal hemorrhage
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Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71.

Organs Large vs Medium vs Small vs
Skin - Digital gangrene, Palpable purpura
Livedo reticularis
MSK PMR Arthritis, myositis Arthritis
Heart AR, hypertension Coronary vasculitis Myocarditis, pericarditis
Lungs - PHT Alveolar hemorrhage
Kidney Renal artery stenosis Renovascular HT Glomerulonephritis
GI Bowel angina Bowel angina, GIB, mucous bloody
appendicitis diarrhea
Neuro Optic neuritis Mononeuritis multiplex Polyneuropathy
Eyes Optic neuritis Retinal vasculitis Retinal vasculitis, keratitis,
episcleritis, scleritis
ENT - - Saddle nose, sinusitis
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 How to make the diagnosis?
Investigations Large vs Medium vs Small vs

Angiogram,
ultrasound, PET scan
  -
Renal angiogram
Tissue pathology   
Temporal artery

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 Mimic / secondary causes

Vascular size

Angiogram Immune complex

Negative Positive
Work up or
confirm
diagnosis
Tissue biopsy

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CF. Khon Kaen University Okazaki et al. Gen Fam Med. 2017;18:72–78.
 Proteinase-3

•
20 causes •
Infection: HBV, HCV, HIV, TB
Complement: C3, C4, anti-C1q Ab

Myeloperoxidase

ANA
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C-ANCA Anti-PR3 C-ANCA
P-ANCA Anti-MPO P-ANCA

Anti-PR3
Anti-MPO

Anti-PR3 C-ANCA
Anti-MPO P-ANCA

CF. Khon Kaen University Bossuty et al. Nat Rev Rheum. 2017;13:683-92.
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CLASSIFICATION OF
VASCULITIS
Revised Chapel Hill consensus
conference
(2012)
 Variable size vessel vasculitis
• Behcet’s syndrome
• Cogan’s syndrome (ocular-
inner ear)

Single-organ vasculitis
• Cutaneous small vessel
vasculitis
• Testicular arteritis
• Central nervous system
vasculitis

Vasculitis associated with

systemic disease
• Rheumatoid vasculitis
• Lupus vasculitis, etc.

Vasculitis associated with

probable etiology
• Hydralazine-associated MPA
• HBV-associated vasculitis, etc.
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Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71.
 Large vessel vasculitis
Disease Clinical Investigations
TKA • Pre-pulseless: nonspecific symptoms ESR, aortogram, CTA, MRA,
• Vascular inflam: vascular pain and PET scan
tenderness (irregular tapering & narrowing
• Fibrotic: bruit & ischemia (HT / stroke + aneurysm beading)
in the young, claudication)

GCA Headache, PMR, jaw claudication, ESR, ultrasound temporal

vascular tenderness, visual loss (15% vessel, temporal artery biopsy
ischemia from posterior ciliary branch of
opthalmic artery)

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 Circumferential mural
thickening

Mural thickening

Farrah et al. Atheroscler Thromb Vasc Biol. 2019;39:1520-41. Before Rx After18Rx

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 Large vessel vasculitis treatment
Disease Treatments
TKA Prednisolone 0.5-1 MKD
MTX 5-15 mg/week
CYC 1-2 MKD oral or 0.3-0.75 mg/m2 iv
Cyclosporin A 3 MKD
Azathioprine 2 MKD
MMF 1.5-3 g/d
Infliximab 3 mg/kd
Tocilizumab 8 mg/kg monthly
GCA Prednisolone 1 MKD until normal ESR
Tape 5 mg q 1-2 wk to 30 mg/d
Tape 2.5 mg q 1-2 wk to 15 mg
Tape 2.5 mg q 4 wk to 7.5 mg/d
CF. Khon Kaen University Tape 2.5 mg q 12 wk until off
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 Medium vessel vasculitis (PAN)

Myalgia / arthritis
Testicular pain Hypertension
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Polyarteritis nodosa
• Investigation
• HBV
• Angiogram
• Biopsy
• Sural nerve
• Testicle
• Muscle
• Skin with subcutaneous

Be careful for aneurysm

Farrah et al. Atheroscler Thromb Vasc Biol. 2019;39:1520-41.
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•
Cutaneous PAN
NSAIDs
• Colchicine
• + Steroid
• + Dapsone
• + Immunosuppressant
HBV infection
Antiviral drug + short term
steroid dose 0.5-1 MKD +
plasmapharesis
Five factors score
(Revised 2011)
• Age > 65 years
• Cr > 1.7 mg/dL
• GI involvement
• Cardiac involvement
• No ENT involvement
Polyarteritis nodosa treatment
No HBV infection
No severe visceral organ Severe visceral organ
involvement (CNS, GI, kidney) involvement (CNS, GI, kidney)
Steroid 0.5-1 MKD depend on • High dose steroid + IV CYC
severity • AZA or MTX for maintenance
+ steroid sparing
immunosuppressant
(AZA or MTX)
Response to treatment
Yes No
Tapering dose of steroid • CYC IV monthly x 6
• Oral CYC 0.5-2 MKD
• Azathioprine / MTX / etc.
Virgilio et al. Autoimmune Rev. 2016;15(6):564-70.
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 ANCA associated vasculitis

Asthma in elderly onset

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 ANCA associated vasculitis

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Farrah et al. Atheroscler Thromb Vasc Biol. 2019;39:1520-41.
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CF. Khon Kaen University Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71.
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CF. Khon Kaen University Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71.
 Clinical manifestations
GPA EGPA MPA
Signs and • Pulmonary renal • Prodromal (3-7y): AR, • Pulmonary renal
symptoms syndrome asthma polyposis syndrome
• Triad of organ • Blood and tissue • leukocytoclastic
involvement eosinophilia vasculitis
- upper respir tract • Life threatening systemic • RPGN
- lower respir tract vasculitis
- kidney
Investigation Biopsy CBC, biopsy, p-ANCA, Biopsy, p-ANCA, anti-
c-ANCA, anti-PR3 anti-MPO MPO
Pathology Granulomatous, Granulomatous with Fibrinoid necrotizing
crescentric eosinophil infiltration, vasculitis, crescentric
glomerulonephritis crescentric GN glomerulonephritis
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 MTX or MMF*

CF. Khon Kaen University *Non-organ-life threatening 29

Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71.
 Pathology guides treatment options
Granulomatous lesion Fibrinoid necrosis
• Giant cell arteritis • Polyarteritis nodosa (PAN)
• Takayasu’s arteritis • Microscopic polyangiitis (MPA)
• Eosinophilic granulomatous with • Secondary vasculitis (SLE, DM)
polyangiitis (EGPA) • Granulomatosis with polyangiitis (GPA)
• Localized granulomatosis with
polyangiitis

Steroid high dose

+
Steroid high dose immunosuppressant
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Answer the questions
• When do we suspect systemic vasculitis? Clinical syndrome
• What is/are differential diagnosis of vasculitis? Vasculitis mimic
• What are the classical clinical characteristics of vasculitis? Vascular size
• How can we make the diagnosis of vasculitis? Investigations
• What are the vasculitis treatments? Treatment

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THANK YOU