lectura de vasculitis.pdf

Harrison’s Lecture Notes

Copyright © The McGraw-Hill Companies. All rights reserved.

Vasculitis

Carol A. Langford, MD, MHS

Director, Center for Vasculitis Care and Research

Department of Rheumatic and Immunologic Diseases

Cleveland Clinic Foundation



Lecture Rationale and Objectives

Lecture Rationale: • The vasculitic diseases are uncommon entities that often present first to internists and family medicine physicians

• Suspicion is essential because certain forms of vasculitis

are organ and life threatening

• Recognition and early diagnosis of vasculitis plays an important

role in preventing morbidity and even mortality

Lecture Objectives: • Identify the spectrum of the vasculitic diseases

• Recognize the clinical manifestations of vasculitis

• Develop a diagnostic approach to vasculitis



Blood vessel damage

Thickening of vessel wall Attenuation of vessel wall

Aneurysm formation or

Disruption of the vessel wall

with hemorrhage into tissue

Tissue or organ ischemia

Luminal narrowing

or occlusion Vessel wall thinning

Vasculitis = Inflammation of the Blood Vessel



Vasculitis: Histological and Clinical Correlation

Palpable Purpura Disruption of the vessel wall with

red blood cell extravasation into tissue

Copyright © The McGraw-Hill Companies, Inc. All

rights reserved.

Courtesy of Carol A. Langford



Giant cell arteritis

Takayasu’s arteritis

Kawasaki disease

Polyarteritis nodosa

Wegener’s granulomatosis

Microscopic polyangiitis

Churg-Strauss syndrome

Henoch-Schönlein purpura

Medications

Infection

Malignancy

Transplant

Cryoglobulinemia

Connective tissue disease

(Rheumatoid arthritis, SLE

Inflammatory myositis)

Primary Vasculitides Secondary Vasculitides

Vasculitis occurring secondary to an underlying disease or exposure

Unique disease entities without a currently identified underlying cause

where vasculitis forms the pathological basis of tissue injury

Vasculitis Is Not One Specific Disease

Blood vessel inflammation can be seen in a variety of settings



How Do Forms of Primary Vasculitis Differ?

Epidemiology: Age, sex, ethnicity, frequency

Clinical Manifestations: Symptoms, signs

Patterns of organ involvement

Diagnosis: Clinical and laboratory features

Biopsy (granulomas, eosinophils)

Arteriography

Treatment and Outcome: Supportive care and close observation

Prednisone

Cytotoxic therapy (cyclophosphamide)

Predominant vessel size: Large, medium, small vessel



Large Vessel

Giant cell arteritis

Takayasu’s arteritis

Medium Vessel

Polyarteritis nodosa

Kawasaki disease

Small Vessel




Henoch-Schönlein purpura

Isolated cutaneous vasculitis

Aorta Capillary Vein

Vessel size plays a role in: Symptoms and signs

Methods of diagnostic evaluation



Large Vessel Vasculitis

Aorta, main branches of the aorta, pulmonary arteries

Aortic aneurysm Subclavian artery stenosis





Large Vessel Vasculitis: Giant Cell Arteritis

(Historically also called temporal arteritis)

• The most common form of primary systemic vasculitis

• Granulomatous large vessel vasculitis

• Occurs in people over the age of 50 (mean age 74)

• 2:1 women:men

• Preferentially involves extracranial branches of the carotid artery



Giant Cell Arteritis

Clinical Features:

• Headache, Scalp tenderness, jaw / tongue claudication

• Visual loss due to optic nerve ischemia from arteritis of ocular vessels

• Fever, fatigue, weight loss

• Polymyalgia rheumatica: pain along shoulder and hip girdle

• Extremity claudication

• Aortic aneurysm

• Nodular, tender, temporal artery with diminished or absent pulsation

• Scalp ischemia

• Absent peripheral pulses, asymmetry of blood pressure in extremities

27% of patients with GCA will have

non-cranial large vessel disease

Physical examination:




Laboratories:

Diagnosed by:

Reflective of an inflammatory process:

• CBC: anemia, thrombocytosis, leukocytosis

• Elevated erythrocyte sedimentation rate (ESR), C-reactive protein

Temporal artery biopsy

(+) 50-80%





• Prednisone 40-60 mg daily - Reduces symptoms and prevents visual loss

- Begin immediately while biopsy is being arranged

Treatment:

Outcome:

• 70% relapse require increased prednisone

• 35-85% have prednisone side effects

• Overall no difference in survival

• 18x higher rate of thoracic aortic aneurysms

- May occur as a late complication of disease

- Associated with a high mortality rate

• Aspirin 81 mg daily - May reduce cranial ischemic complications

- Use in all patients without contraindications Courtesy of Carol A. Langford



Medium Vessel Vasculitis

Vessel examples: GI tract, nerve, digits, interlobular renal

Mesenteric Arteriogram

Microaneurysms, stenoses, beading

Biopsy

Vessel supplying sural nerve

Courtesy of Carol A. Langford Copyright © The McGraw-Hill Companies, Inc. All rights reserved.



Medium Vessel Vasculitis: Polyarteritis Nodosa

• First form of vasculitis described

– Systemic features

– Nerve

– Renal

– GI tract

– Digital infarction

Fever, weight loss, arthralgias, night sweats

Mononeuritis multiplex (ie: foot drop, wrist drop)

Hypertension, infarction

Pain, infarction, perforation, bleeding

Ischemic finger / toe

Often presents with acute severe disease

Clinical Features:



Polyarteritis Nodosa

Laboratories:

Diagnosed by:

Treatment:

Elevated ESR

Anemia, mild elevations in WBC and platelets

May see LFT abnormalities, microscopic hematuria

A PAN-like vasculitis can occur with hepatitis B or C

Arteriography, biopsies

Prednisone + cyclophosphamide

Prednisone alone for non-severe disease

Antiviral treatment if hepatitis B or C are present



Small Vessel Vasculitis

Capillary, arteriole, venule

Alveolar hemorrhage Glomerulonephritis Copyright © The McGraw-Hill Companies, Inc. All rights reserved.

Courtesy of Carol A. Langford Courtesy of Carol A. Langford




Small Vessel Vasculitis: Wegener’s Granulomatosis

Sinus (>95%) Lung (85%) Kidney (80%)

Proteinuria,

Hematuria

Red blood cell casts

Detected by urinalysis:

20% at diagnosis

80% during course

Can be rapidly progressive

Typically asymptomatic

May lead to renal failure






Antineutrophil Cytoplasmic Antibodies (ANCA)

Myeloperoxidase (MPO) Proteinase 3 (PR3)

cANCA

cytoplasmic staining

pANCA

perinuclear staining

Target Antigens

In Vasculitis

PR3-ANCA MPO-ANCA




75-90% 5-20% up to 20%

10-50% 50-80% up to 20%

3-20% 2-40% up to 60%

ANCA (-)

Courtesy of Carol A. Langford Courtesy of Carol A. Langford



Key Clinical Issues Regarding ANCA

• Can ANCA be used to diagnose Wegener’s granulomatosis?

Usually no – because of the toxicity of therapy and the need for

diagnostic precision biopsy still required in most people

• Do high ANCA levels indicate active vasculitis?

No - In large cohorts, ANCA levels are higher overall in active disease

but…..

In individual patients ANCA does not correlate with disease activity

and should not be used alone to guide treatment

ANCA can be helpful but is not necessary for diagnosis



Wegener’s Granulomatosis

Diagnosed by:

Treatment:

Typically biopsy

Prednisone + cyclophosphamide

Prednisone + methotrexate (non-severe disease)

Outcome: Survival: Untreated: 5 months

Treatment: 80% survival

Challenges: Damage from prior disease

Treatment related toxicity

50-70% relapse



Small Vessel Vasculitis: Cutaneous Vasculitis

Cutaneous vasculitis represents the most common

vasculitic manifestation encountered in clinical practice

Copyright © The McGraw-Hill Companies, Inc. All rights reserved.



Small Vessel Vasculitis: Cutaneous Vasculitis

< 30% no identified cause or disease outside of the skin

• Medication

• Infection

• Malignancy

• Connective tissue disease

• Heralding feature of a primary systemic vasculitis

> 70% occur in the setting of an underlying process:

Treatment of isolated cutaneous vasculitis:

• Do not overtreat: recognize that this is not threatening

• Avoid the use of toxic immunosuppressive agents



You see a patient with a possible cutaneous vasculitis

What do you need to do?

1. Recognize if a patient is in a potentially threatening situation

2. Confirm that this is vasculitis

3. Determine if there is an underlying cause for the vasculitis

How do you do this?



Recognition of Vasculitis

Skin + +

Eye + +

ENT + + +

Lung + / - + / - +

Kidney +

GI + + + +

Neuro + + +

History Exam Labs Imaging



Assessment of Vasculitis

• Do a complete review of systems

• Medications: includes over-the-counter, supplements, recreational drugs

History

Physical Examination

• Provides clues of organ involvement, features of an underlying disease

Laboratories

Urinalysis (if (+) blood, check their creatinine immediately)

Chemistries (to include creatinine and hepatic)

CBC with differential

ESR, CRP

Always

Perform

Systemic vasculitis

Connective tissue disease

Infection

Neoplasm

Pursue additional lab testing if

there are features that point towards:



Assessment of Vasculitis

Imaging

Chest imaging (CXR, CT)

Pursue CT, MRI, arteriography of other sites as clinically indicated

• Perform in all patients with pulmonary symptoms

• No pulmonary symptoms: obtain imaging if there are other features

that suggest a systemic small vessel vasculitis

Biopsy

• Lesions that looks like vasculitis may not be

• If disease is outside of the skin, these are usually better locations

for biopsy to confirm a systemic vasculitis



Recognizing Vasculitis: Suspicion is the Key

Any instance of:

• Palpable purpura

• Pulmonary hemorrhage

• Glomerulonephritis

• Ischemic digits

• Mononeuritis multiplex (wrist or foot drop)

• Worsening sinus symptoms not responsive to treatment

• Unexplained multisystem disease

• Unexplained pulmonary infiltrates

• Rapidly progressive major organ dysfunction

Consider also in the setting of:



What to do if a Vasculitis is Suspected

• Rule out potentially organ- or life-threatening disease

- Remember asymptomatic kidney and lung disease

• Categorize where possible to a specific disease entity

- Consider pattern of features

• Pursue means of a definitive diagnosis • Select treatment based upon diagnosis and its severity • Seek out consultation early as directed by clinical features

Further information on vasculitis can be found in: Harrison’s Principles of Internal Medicine, 17e

Chapter 319: The Vasculitis Syndromes

By Carol A. Langford and Anthony S. Fauci



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