lectures vasculitis

Harrison’s Lecture NotesCopyright © The McGraw-Hill Companies. All rights reserved.

VasculitisCarol A. Langford, MD, MHSDirector, Center for Vasculitis Care and ResearchDepartment of Rheumatic and Immunologic Diseases

Cleveland Clinic Foundation


Lecture Rationale and ObjectivesLecture Rationale and Objectives

Lecture Rationale:Lecture Rationale:

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

• Suspicion is essential because certain forms of vasculitis Suspicion is essential because certain forms of vasculitis are organ and life threatening are organ and life threatening

• Recognition and early diagnosis of vasculitis plays an important Recognition and early diagnosis of vasculitis plays an important role in preventing morbidity and even mortality role in preventing morbidity and even mortality

Lecture Objectives:Lecture Objectives:

• Identify the spectrum of the vasculitic diseasesIdentify the spectrum of the vasculitic diseases• Recognize the clinical manifestations of vasculitisRecognize the clinical manifestations of vasculitis• Develop a diagnostic approach to vasculitisDevelop a diagnostic approach to vasculitis


Blood vessel damageBlood vessel damage

Thickening of vessel wall Attenuation of vessel wallThickening of vessel wall Attenuation of vessel wall

Aneurysm formation orAneurysm formation orDisruption of the vessel wallDisruption of the vessel wallwith hemorrhage into tissuewith hemorrhage into tissue

Tissue or organ ischemiaTissue or organ ischemia

Luminal narrowing Luminal narrowing or occlusionor occlusion Vessel wall thinningVessel wall thinning

Vasculitis = Inflammation of the Blood VesselVasculitis = Inflammation of the Blood Vessel


Vasculitis: Histological and Clinical CorrelationVasculitis: Histological and Clinical Correlation

Palpable PurpuraPalpable PurpuraDisruption of the vessel wall with Disruption of the vessel wall with

red blood cell extravasation into tissuered blood cell extravasation into tissue

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

Courtesy of Carol A. Langford


Giant cell arteritisGiant cell arteritisTakayasu’s arteritisTakayasu’s arteritisKawasaki diseaseKawasaki diseasePolyarteritis nodosaPolyarteritis nodosaWegener’s granulomatosisWegener’s granulomatosisMicroscopic polyangiitis Microscopic polyangiitis Churg-Strauss syndromeChurg-Strauss syndromeHenoch-SchHenoch-Schöönlein purpuranlein purpura

MedicationsMedicationsInfectionInfectionMalignancyMalignancyTransplantTransplantCryoglobulinemiaCryoglobulinemiaConnective tissue diseaseConnective tissue disease (Rheumatoid arthritis, SLE(Rheumatoid arthritis, SLE Inflammatory myositis)Inflammatory myositis)

Primary VasculitidesPrimary Vasculitides Secondary VasculitidesSecondary Vasculitides

Vasculitis occurring secondaryVasculitis occurring secondary to an underlying disease or exposureto an underlying disease or exposure

Unique disease entities without a Unique disease entities without a currently identified underlying causecurrently identified underlying cause

where vasculitis forms the where vasculitis forms the pathological basis of tissue injurypathological 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?How Do Forms of Primary Vasculitis Differ?

Epidemiology:Epidemiology: Age, sex, ethnicity, frequencyAge, sex, ethnicity, frequency

Clinical Manifestations: Clinical Manifestations: Symptoms, signsSymptoms, signs Patterns of organ involvementPatterns of organ involvement

Diagnosis:Diagnosis: Clinical and laboratory features Clinical and laboratory features Biopsy (granulomas, eosinophils)Biopsy (granulomas, eosinophils) ArteriographyArteriography

Treatment and Outcome: Treatment and Outcome: Supportive care and close observationSupportive care and close observation PrednisonePrednisone Cytotoxic therapy (cyclophosphamide)Cytotoxic therapy (cyclophosphamide)

Predominant vessel size:Predominant vessel size: Large, medium, small vesselLarge, medium, small vessel


Large Vessel

Giant cell arteritis Takayasu’s arteritis

Medium Vessel

Polyarteritis nodosa Kawasaki disease

Small Vessel

Wegener’s granulomatosisMicroscopic polyangiitis

Churg-Strauss syndrome

Henoch-Schönlein purpura

Isolated cutaneous vasculitis

Aorta Capillary Vein

Vessel size plays a role in: Symptoms and signsMethods of diagnostic

evaluation


Large Vessel VasculitisLarge Vessel Vasculitis

Aorta, main branches of the aorta, pulmonary arteriesAorta, main branches of the aorta, pulmonary arteries

Aortic aneurysmAortic aneurysm Subclavian artery stenosisSubclavian artery stenosis




Large Vessel Vasculitis: Giant Cell ArteritisLarge Vessel Vasculitis: Giant Cell Arteritis

(Historically also called temporal arteritis)(Historically also called temporal arteritis)

• The most common form of primary systemic vasculitisThe most common form of primary systemic vasculitis

• Granulomatous large vessel vasculitis Granulomatous large vessel vasculitis

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

• 2:1 women:men2:1 women:men

• Preferentially involves extracranial branches of the carotid arteryPreferentially involves extracranial branches of the carotid artery


Giant Cell ArteritisGiant Cell Arteritis

Clinical Features:Clinical Features:

• Headache, Scalp tenderness, jaw / tongue claudicationHeadache, Scalp tenderness, jaw / tongue claudication• Visual loss due to optic nerve ischemia from arteritis of ocular vesselsVisual loss due to optic nerve ischemia from arteritis of ocular vessels

• Fever, fatigue, weight lossFever, fatigue, weight loss

• Polymyalgia rheumatica: pain along shoulder and hip girdlePolymyalgia rheumatica: pain along shoulder and hip girdle

• Extremity claudicationExtremity claudication• Aortic aneurysmAortic aneurysm

• Nodular, tender, temporal artery with diminished or absent pulsationNodular, tender, temporal artery with diminished or absent pulsation• Scalp ischemiaScalp ischemia• Absent peripheral pulses, asymmetry of blood pressure in extremitiesAbsent peripheral pulses, asymmetry of blood pressure in extremities

27% of patients with GCA will have 27% of patients with GCA will have non-cranial large vessel diseasenon-cranial large vessel disease

Physical examination:Physical examination:



Laboratories:Laboratories:

Diagnosed by:Diagnosed by:

Reflective of an inflammatory process:Reflective of an inflammatory process:• CBC: anemia, thrombocytosis, leukocytosisCBC: anemia, thrombocytosis, leukocytosis• Elevated erythrocyte sedimentation rate (ESR), C-reactive proteinElevated erythrocyte sedimentation rate (ESR), C-reactive protein

Temporal artery biopsyTemporal artery biopsy

(+) 50-80%(+) 50-80%




• Prednisone 40-60 mg dailyPrednisone 40-60 mg daily- Reduces symptoms and prevents visual loss- Reduces symptoms and prevents visual loss- - Begin immediately while biopsy is being arrangedBegin immediately while biopsy is being arranged

Treatment:Treatment:

Outcome:Outcome:• 70% relapse require increased prednisone70% relapse require increased prednisone• 35-85% have prednisone side effects35-85% have prednisone side effects• Overall no difference in survivalOverall no difference in survival• 18x higher rate of thoracic aortic aneurysms18x higher rate of thoracic aortic aneurysms - May occur as a late complication of disease- May occur as a late complication of disease - Associated with a high mortality rate- Associated with a high mortality rate

• Aspirin 81 mg dailyAspirin 81 mg daily - May reduce cranial ischemic complications- May reduce cranial ischemic complications - Use in all patients without contraindications- Use in all patients without contraindications



Medium Vessel VasculitisMedium Vessel Vasculitis

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

Mesenteric ArteriogramMesenteric Arteriogram

Microaneurysms, stenoses, beading Microaneurysms, stenoses, beading

BiopsyBiopsy

Vessel supplying sural nerveVessel supplying sural nerveCourtesy of Carol A. LangfordCopyright © The McGraw-Hill Companies, Inc. All rights reserved.


Medium Vessel Vasculitis: Polyarteritis NodosaMedium Vessel Vasculitis: Polyarteritis Nodosa

• First form of vasculitis describedFirst form of vasculitis described

– Systemic features Systemic features

– NerveNerve

– RenalRenal

– GI tractGI tract

– Digital infarctionDigital infarction

Fever, weight loss, arthralgias, night sweatsFever, weight loss, arthralgias, night sweats

Mononeuritis multiplex (ie: foot drop, wrist drop)Mononeuritis multiplex (ie: foot drop, wrist drop)

Hypertension, infarctionHypertension, infarction

Pain, infarction, perforation, bleedingPain, infarction, perforation, bleeding

Ischemic finger / toeIschemic finger / toe

Often presents with acute severe diseaseOften presents with acute severe disease

Clinical Features:Clinical Features:


Polyarteritis NodosaPolyarteritis Nodosa

Laboratories:Laboratories:



Elevated ESRElevated ESRAnemia, mild elevations in WBC and plateletsAnemia, mild elevations in WBC and plateletsMay see LFT abnormalities, microscopic hematuriaMay see LFT abnormalities, microscopic hematuriaA PAN-like vasculitis can occur with hepatitis B or CA PAN-like vasculitis can occur with hepatitis B or C

Arteriography, biopsiesArteriography, biopsies

Prednisone + cyclophosphamidePrednisone + cyclophosphamidePrednisone alone for non-severe diseasePrednisone alone for non-severe diseaseAntiviral treatment if hepatitis B or C are presentAntiviral treatment if hepatitis B or C are present


Small Vessel VasculitisSmall Vessel Vasculitis

Capillary, arteriole, venuleCapillary, arteriole, venule

Alveolar hemorrhageAlveolar hemorrhage GlomerulonephritisGlomerulonephritisCopyright © The McGraw-Hill Companies, Inc. All rights reserved.

Courtesy of Carol A. LangfordCourtesy of Carol A. Langford



Small Vessel Vasculitis: Wegener’s GranulomatosisSmall Vessel Vasculitis: Wegener’s Granulomatosis

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

Proteinuria, Proteinuria, HematuriaHematuria

Red blood cell castsRed blood cell casts

Detected by urinalysis:Detected by urinalysis:

20% at diagnosis20% at diagnosis80% during course80% during course

Can be rapidly progressiveCan be rapidly progressiveTypically asymptomaticTypically asymptomaticMay lead to renal failureMay lead to renal failure





Antineutrophil Cytoplasmic Antibodies (ANCA)Antineutrophil Cytoplasmic Antibodies (ANCA)

Myeloperoxidase (MPO)Myeloperoxidase (MPO) Proteinase 3 (PR3)Proteinase 3 (PR3)

cANCA cytoplasmic staining

pANCAperinuclear staining

Target AntigensTarget AntigensIn VasculitisIn Vasculitis

PR3-ANCAPR3-ANCA MPO-ANCAMPO-ANCAWegener’s granulomatosis Wegener’s granulomatosis Microscopic polyangiitisMicroscopic polyangiitisChurg-Strauss syndromeChurg-Strauss syndrome

75-90% 5-20%75-90% 5-20% up to 20%up to 20%10-50% 50-80%10-50% 50-80% up to 20%up to 20% 3-20%3-20% 2-40% 2-40% up to 60%up to 60%

ANCA (-)ANCA (-)

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


Key Clinical Issues Regarding ANCAKey Clinical Issues Regarding ANCA

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

Usually no – because of the toxicity of therapy and the need for Usually no – because of the toxicity of therapy and the need for diagnostic precision biopsy still required in most peoplediagnostic precision biopsy still required in most people

• Do high ANCA levels indicate active vasculitis?Do high ANCA levels indicate active vasculitis?

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

but….. but…..

In individual patients ANCA In individual patients ANCA does notdoes not correlate with disease activity correlate with disease activity

and and should notshould not be used alone to guide treatment be used alone to guide treatment

ANCA can be helpful but is not necessary for diagnosisANCA can be helpful but is not necessary for diagnosis


Wegener’s GranulomatosisWegener’s Granulomatosis



Typically biopsyTypically biopsy

Prednisone + cyclophosphamidePrednisone + cyclophosphamidePrednisone + methotrexate (non-severe disease)Prednisone + methotrexate (non-severe disease)

Outcome:Outcome: Survival:Survival:Untreated: 5 months Untreated: 5 months Treatment: 80% survival Treatment: 80% survival

Challenges:Challenges:Damage from prior diseaseDamage from prior diseaseTreatment related toxicityTreatment related toxicity50-70% relapse50-70% relapse


Small Vessel Vasculitis: Cutaneous VasculitisSmall Vessel Vasculitis: Cutaneous Vasculitis

Cutaneous vasculitis represents the most common Cutaneous vasculitis represents the most common vasculitic manifestation encountered in clinical practicevasculitic manifestation encountered in clinical practice

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


Small Vessel Vasculitis: Cutaneous VasculitisSmall Vessel Vasculitis: Cutaneous Vasculitis

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

• MedicationMedication• InfectionInfection• MalignancyMalignancy• Connective tissue diseaseConnective tissue disease• Heralding feature of a primary systemic vasculitisHeralding feature of a primary systemic vasculitis

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

Treatment of isolated cutaneous vasculitis:Treatment of isolated cutaneous vasculitis:

• Do not overtreat: recognize that this is not threateningDo not overtreat: recognize that this is not threatening• Avoid the use of toxic immunosuppressive agentsAvoid the use of toxic immunosuppressive agents


You see a patient with a possible cutaneous vasculitisYou see a patient with a possible cutaneous vasculitis

What do you need to do?What do you need to do?

1.1. Recognize if a patient is in a potentially threatening situationRecognize if a patient is in a potentially threatening situation

2.2. Confirm that this is vasculitisConfirm that this is vasculitis

3.3. Determine if there is an underlying cause for the vasculitisDetermine if there is an underlying cause for the vasculitis

How do you do this?How do you do this?


Recognition of VasculitisRecognition of Vasculitis

SkinSkin + +

EyeEye + +

ENTENT + + +

LungLung + / - + / - +

KidneyKidney +

GIGI + + + +

NeuroNeuro + + +

History Exam Labs ImagingHistory Exam Labs Imaging


Assessment of VasculitisAssessment of Vasculitis

• Do a complete review of systemsDo a complete review of systems• Medications: includes over-the-counter, supplements, recreational drugsMedications: includes over-the-counter, supplements, recreational drugs

HistoryHistory

Physical ExaminationPhysical Examination

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

LaboratoriesLaboratories

Urinalysis (if (+) blood, check their creatinine immediately)Urinalysis (if (+) blood, check their creatinine immediately)Chemistries (to include creatinine and hepatic)Chemistries (to include creatinine and hepatic)CBC with differentialCBC with differentialESR, CRPESR, CRP

AlwaysAlwaysPerformPerform

Systemic vasculitisSystemic vasculitisConnective tissue diseaseConnective tissue diseaseInfectionInfectionNeoplasmNeoplasm

Pursue additional lab testing if Pursue additional lab testing if there are features that point towards:there are features that point towards:


Assessment of VasculitisAssessment of Vasculitis

ImagingImaging

Chest imaging (CXR, CT)Chest imaging (CXR, CT)

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

• Perform in all patients with pulmonary symptomsPerform in all patients with pulmonary symptoms• No pulmonary symptoms: obtain imaging if there are other featuresNo pulmonary symptoms: obtain imaging if there are other features that suggest a systemic small vessel vasculitisthat suggest a systemic small vessel vasculitis

BiopsyBiopsy

• Lesions that looks like vasculitis may not beLesions that looks like vasculitis may not be

• If disease is outside of the skin, these are usually better locations If disease is outside of the skin, these are usually better locations for biopsy to confirm a systemic vasculitisfor biopsy to confirm a systemic vasculitis


Recognizing Vasculitis: Suspicion is the KeyRecognizing Vasculitis: Suspicion is the Key

Any instance of:Any instance of:• Palpable purpuraPalpable purpura• Pulmonary hemorrhage Pulmonary hemorrhage • GlomerulonephritisGlomerulonephritis• Ischemic digitsIschemic digits• Mononeuritis multiplex (wrist or foot drop)Mononeuritis multiplex (wrist or foot drop)

• Worsening sinus symptoms not responsive to treatment Worsening sinus symptoms not responsive to treatment • Unexplained multisystem diseaseUnexplained multisystem disease• Unexplained pulmonary infiltratesUnexplained pulmonary infiltrates• Rapidly progressive major organ dysfunctionRapidly progressive major organ dysfunction

Consider also in the setting of:Consider also in the setting of:


What to do if a Vasculitis is SuspectedWhat to do if a Vasculitis is Suspected

• Rule out potentially organ- or life-threatening diseaseRule out potentially organ- or life-threatening disease - - Remember asymptomatic kidney and lung diseaseRemember asymptomatic kidney and lung disease

• Categorize where possible to a specific disease entityCategorize where possible to a specific disease entity - - Consider pattern of featuresConsider pattern of features

• Pursue means of a definitive diagnosisPursue means of a definitive diagnosis

• Select treatment based upon diagnosis and its severitySelect treatment based upon diagnosis and its severity

• Seek out consultation early as directed by clinical featuresSeek out consultation early as directed by clinical features

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

Chapter 319: The Vasculitis SyndromesChapter 319: The Vasculitis SyndromesBy Carol A. Langford and Anthony S. Fauci By Carol A. Langford and Anthony S. Fauci


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