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Systemic Vasculitis:

Principles of Diagnosis and Treatment

Boca Raton Regional Hospital

14th Annual Internal Medicine Conference 2017

Benjamin Wang, M.D., FRCPC

Division of Rheumatology

Mayo Clinic

Jacksonville, FL

Disclosures

• Nothing to disclose

Topics

• Diagnosing vasculitis

– When to suspect

– Skin can be the key!

– Taking inventory

– Diagnostic tests and procedures

• Vasculitis Syndromes Overview

• New Therapies

Suspect systemic vasculitis when these

four cardinal clues are present:

• Multisystem disease

• Constitutional symptoms

• Skin manifestations

• Mononeuritis multiplex

Suspecting Vasculitis: Multisystem

Disease

• Common categories of multisystem disease – Systemic vasculitis

– Systemic autoimmune/connective tissue disorders

– Infectious disease

– Malignancy

– Drug toxicity

– Endocrinopathies

Suspecting Vasculitis: Multisystem

Disease

• Systemic vasculitis becomes all the more likely when there are ischemic and/or inflammatory manifestations: – Inflammatory damage

• Pulmonary

• Renal

• Cutaneous

– Infarction

• Skin and soft tissue

• Nerve

• Cerebral

• Abdominal

• Myocardial

Suspecting Vasculitis

• Constitutional Symptoms

• Fever

• Loss of appetite

• Night sweats

• Weight loss

• May all be severe (cachexia)

Suspecting Vasculitis

• The skin is often the key • Maculopapular rash

• Palpable purpura

• Nodose lesions

• Urticaria

• Hemorrhagic

• Livedo reticularis

• > 24 hours’ duration

Biopsy skin if possible

Take Inventory

• Focus on these major systems: – Dermatologic

– Pulmonary

– Neurological

– Renal

• Investigate if any symptoms – Dermatologic: skin biopsy

– Pulmonary: PFT, CXR, CT scan, biopsy

– Neurologic: nerve conduction studies, biopsy (sural nerve)

– Renal: urinalysis, biopsy

– Laboratory: ESR, CRP, ANA, “autoimmune panel,” ANCA

– Imaging: MRA, PET

Mononeuritis multiplex

Sural Nerve Biopsy

Renal Biopsy

CT Chest: Cavitary Lesions

Classification of Vasculitis

Jeanette and Falk 2013. ARTHRITIS & RHEUMATISM 65:1–11.

ANCA antibody positivity

Disease

% positive

Pattern

c-ANCA

p-ANCA

Polysystemic Wegener’s

95%

95%

5%

Limited Wegener’s

60%

90%

10%

Vasculitis in RA, PAN,

SLE , EGPA

5%-20%

0

100%

Idiopathic crescentic

nephritis

85%

40%

60%

Microscopic polyarteritis

60%-75%

15%

85%

Ulcerative colitis

40%-80%

0

100%

Crohn’s disease

10%-40%

0

100%

Classification of Vasculitis

Vasculitis with Underlying Disease

“Very Miscellaneous” Types of Vasculitis

Vasculitis Descriptions

Large-sized vessel vasculitis – aorta and the largest branches directed toward major body

regions (eg, to the extremities and the head and neck)

• Giant cell (temporal) arteritis

• Granulomatous arteritis of the aorta and its major branches, with a predilection for the extracranial branches of the carotid artery. Often involves the temporal artery. Usually occurs in patients over 50 y and is often associated with polymyalgia rheumatica.

• Takayasu arteritis

• Granulomatous arteritis of the aorta and its major branches. Usually occurs in female patients under 50 y.

Jeanette and Falk 2013. ARTHRITIS & RHEUMATISM 65:1–11.

Medium-sized vessel vasculitis – the main visceral arteries (eg, renal, hepatic,

coronary, and mesenteric arteries)

Polyarteritis nodosa

• Necrotizing inflammation of medium- or small-sized arteries, without glomerulonephiritis or vasculitis in arterioles, capillaries, or venules, not associated with ANCA.

• Mesenteric, renal, coronary arteries affected

Kawasaki disease

• Arteritis involving large-, medium-, and small-sized arteries, and associated with mucocutaneous lymph node syndrome. Coronary arteries are often involved. Aorta and large arteries may be involved. Usually occurs in infants and children.

Vasculitis Descriptions Jeanette and Falk 2013. ARTHRITIS & RHEUMATISM 65:1–11.

Vasculitis Descriptions

ANCA-associated small vessel vasculitis – venules, capillaries, arterioles, and the intraparenchymal distal arteries that connect with arterioles

• Granulomatous inflammation

• ENT (Sinuses)

• Lungs

• Kidneys

Granulomatosis with polyangiitis

(GPA; Wegener’s)

• Eosinophil-rich and granulomatous inflammation involving the respiratory tract, associated with asthma and eosinophilia.

Eosinophilic granulomatosus with polyangiitis

(EPA; Churg-Strauss)

• Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs.

Microscopic polyangiitis (MPA)

Jeanette and Falk 2013. ARTHRITIS & RHEUMATISM 65:1–11.

Vasculitis Descriptions

Other Small Vessel Vasculitis

IgA vasculitis (Henoch-

Schönlein)

Vasculitis, with IgA-dominant immune deposits, affecting small-sized vessels (ie, capillaries,

venules, or arterioles). Typically involves skin (palpable purpura), gut and glomeruli, and is

associated with arthralgias or arthritis.

Essential cryoglobulinemia

vasculitis

Vasculitis, with cryoglobulin immune deposits, affecting small-sized vessels (ie, capillaries, venules, or arterioles), and associated with

cryoglobulins in serum. Skin and glomeruli are often involved.

Cutaneous leukocytoclastic

angiitis

Isolated cutaneous leukocytoclastic angiitis without systemic vasculitis or glomerulonephritis.

Look for allergy/hypersensitivity.

Jeanette and Falk 2013. ARTHRITIS & RHEUMATISM 65:1–11.

Case Presentation 1A

• 68 year old Caucasian female

admitted for progressive dyspnea

• Found to be in clinical congestive

heart failure

– severe aortic regurgitation

– aortic root dilatation

• History of polymyalgia rheumatica 10

years ago, treated with prednisone

taper. No subsequent flares; now off

steroids.

• History negative for syphilis,

inflammatory arthritis, cardiovascular

risk factors

Preoperative CT Angiogram

Large Vessel Giant Cell

Arteritis

• Clinical syndrome in the spectrum of

polymyalgia rheumatica (PMR) and

cranial giant cell arteritis (GCA) – 15%

of GCA

– The features of PMR are common but

symptoms of cranial GCA are often

absent

– Be vigilant for distal vascular ischemic

features and constitutional symptoms

• Requires more aggressive treatment

• Monitor for late sequelae – aortic

aneurysm and dissection

Neumann T et al. Circulation.2009; 119: 338-339

Pathology: aortitis

• Tissue examination obtained

• Successful repair and synthetic graft of

ascending thoracic aorta and

biomechanical aortic valve

replacement

Giant Cell Arteritis (Temporal Arteritis)

• The most common systemic vasculitis

• Affects persons aged 50+, peak 70-80 years, M:F = 1:2

• Principal vessels involved: – Extracranial vessels from aortic arch (very

common)

– Proximal aortic arch vessels (10-15%)

– Thoracic aorta (< 5%)

– Abdominal aorta and branches (<5%)

GCA: Classification Criteria

• Age of onset 50 years

• New headache

• Temporal artery abnormality on exam

• Elevated ESR 50 mm/h

• Abnormal biopsy

GCA: Symptoms

• Constitutional (50%)

• Cranial Ischemia – Headache (66%) – usually unilateral, focal

– Visual – amaurosis fugax, diplopia, scintillations

– Claudication: Jaw, tongue, face

• Distal Ischemia: limb claudication

• Musculoskeletal symptoms – Polymyalgia rheumatica prodrome – sudden onset stiffness,

pain in shoulder girdle and pelvic girdle

– Swollen hands and feet

– Nonerosive arthritis

GCA: Diagnostic Tests

• ESR 50 mm/h or CRP elevation

• Biopsy of temporal artery – 3-5 cm segment

– May need contralateral side

– May perform in presence of steroids up to 2 weeks

• Diagnostic imaging – CT, MRI

– Angiography (conventional or CT)

– MR Angiography

– PET for large vessel disease

Vasculitis Treatment Principles

1. Immediate immunosuppression

a. Oral steroids up to 1 mg/kg/d

b. IV bolus steroids up to 1000 mg/d x 3 days

c. Plasma exchange

2. Long term immunosuppression

a. Synthetic immunosuppressants: methotrexate, azathioprine,

mycophenolate

b. Biologic immunsuppressants: TNF inhibitors (e.g. etanercept), B

cell depletion (rituximab), anti-IL6 (tocilizumab), etc.

3. Preventive measures

a. Osteoporosis prophylaxis or treatment

b. Infection prophylaxis (esp. PJP)

4. Steroid tapering

Stone JH et al. N Engl J Med 2010;363:221-32.

Villiger PM et al. Lancet 2016; 387:1921–1927

Tocilizumab (anti-IL6) for Giant Cell Arteritis

Prednisone Dose Lowering

• Doses of 40 mg/d or more can be tapered by 10 mg

each step, e.g. 60-50-40 mg

• Doses of 20-40 mg/d can be tapered by 5 mg every

step, e.g. 40-35-30 mg

• Doses of 10-20 mg/d can be tapered by 2.5 mg every

step, e.g. 20-17.5-15-12/5 mg

• Intervals can vary from 5-14 days depending on

severity and potential for relapse

• Below 10 mg/d, reduce by 1 mg every 7-30 days

– Slower tapers in patients on long term steroids are

necessary to prevent relapse and to recover adrenal function

– More rapid tapers can be used in patients with overall

shorter exposures or in milder disease

Conclusion

• Suspect vasculitis with multisystem disease

with constitutional symptoms and specific

organ involvements

• The skin is an important early clue to

vasculitis

• Prepare to “take inventory” with appropriate

investigations

• Recognize GCA and its large vessel variant

• Prepare to use a multidrug approach and

tapering strategies to reduce long term

complications

Thank you

wang.benjamin@mayo.edu