Medium Vessel Vasculitis

Slide 1 · Medium Vessel Vasculitis

Thromboangiitis obliterans • Polyarteritis nodosa • Kawasaki disease

Vascular injury, morphology and clinicopathologic consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define medium vessel vasculitis and recognize overlap between vessel-size categories.

Distinguish Buerger disease, polyarteritis nodosa, and Kawasaki disease by their target vessels and clinical context.

Explain how thrombosis, necrotizing arteritis, and aneurysms generate characteristic complications.

Interpret representative clinical scenarios using morphology and distribution.

Emphasis: Mechanisms → arterial lesions → organ dysfunction.

Slide 3 · Vasculitis: An inflammatory vascular injury

Vessel-wallinflammation

Luminal narrowingor thrombosis

Reduced tissueperfusion

Ischemic injuryor infarction

The affected vascular bed determines the clinical phenotype.

Slide 4 · What defines the medium-vessel group?

Predominantly affects medium-sized muscular arteries and their branches.

Includes visceral arteries, limb arteries, and coronary arteries depending on the entity.

Inflammatory stenoses and aneurysms are characteristic structural consequences.

“Medium vessel” identifies a predilection, not an absolute vessel-size boundary.

The three core entities differ more in distribution and morphology than in caliber alone.

Slide 5 · Three major disorders—three target patterns

Buerger disease

Distal extremity arteries; Thrombosis; Associated venous and nerve involvement.

Polyarteritis nodosa

Systemic muscular arteries; Renal and visceral beds; Necrotizing arteritis.

Kawasaki disease

Childhood mucocutaneous illness; Coronary-artery arteritis and aneurysms.

Anatomical preference is a major diagnostic discriminator.

Slide 6 · Vasculitis is not only a question of size

Classification axes

Predominant artery caliber

Target tissue and vascular bed

Histologic pattern and immune mechanism

Practical constraint

Substantial overlap in affected vessel sizes

Clinical and pathologic exceptions occur

Interpret classification with organ distribution

Slide 7 · How an inflamed artery injures tissue

Inflammatorywall damage

Thrombotic occlusionor stenosis

Downstreamischemia

Pain, ulcerationor infarction

Aneurysm formation reflects weakening rather than merely narrowing the arterial wall.

Slide 8 · Stenosis and aneurysm are different outcomes

Flow-limiting lesion

Intimal thickening or luminal thrombosis

Decreased distal perfusion

Ischemia, pain, infarction

Wall-weakening lesion

Destructive inflammation of arterial wall

Focal dilatation / aneurysm

Potential thrombosis, hemorrhage or rupture

Slide 9 · First-pass differential: Medium-vessel vasculitis

Feature

Buerger disease

PAN

Kawasaki disease

Typical context

Young heavy smoker

Young adults; any age

Infants / young children

Dominant distribution

Distal limbs

Renal / visceral arteries

Coronary arteries

Signature lesion

Inflammatory thrombosis

Segmental necrotizing arteritis

Transmural arteritis; aneurysm

Key threat

Distal gangrene

Visceral / renal ischemia

Myocardial infarction

Slide 10 · Buerger disease: Defining lesion

Also termed thromboangiitis obliterans.

Segmental acute and chronic inflammation with thrombosis of medium arteries.

Especially affects tibial and radial arteries.

Vascular insufficiency is predominantly distal and limb-centered.

The combination of arteritis + occlusive thrombus is essential.

Slide 11 · Buerger disease targets distal arterial beds

Affected muscular arteries

Tibial arteries

Distal lower-limb ischemia

Radial arteries

Distal upper-limb ischemia

Adjacent veins

Superficial nodular phlebitis

Nearby nerves

Intense pain

Distal tissues

Ulceration and gangrene

Tobacco exposure

Strong exposure association

Slide 12 · Tobacco exposure is a central association

Classically occurs in young heavy cigarette smokers.

A strong relationship with cigarette use.

Tobacco exposure may injure the endothelium directly or modify vessel-wall proteins.

The relationship supports prevention but does not establish one proven molecular mechanism.

Association is strong; The exact initiating pathogenesis is incompletely resolved.

Slide 13 · Buerger pathogenesis: Two proposed routes

Direct toxicity hypothesis

A tobacco constituent causes idiosyncratic endothelial injury

Endothelial dysfunction favors vascular inflammation

Immune hypothesis

Tobacco-derived agents alter vascular wall proteins

Host immune response targets the modified structures

Slide 14 · Functional endothelial findings in Buerger

Some affected persons exhibit hypersensitivity to injected tobacco extracts.

Endothelium-dependent vasodilation after acetylcholine challenge may be impaired.

Associations with certain MHC haplotypes support susceptibility.

Neither observation alone constitutes a diagnostic test in this lecture.

Slide 15 · Buerger morphology: Artery and occlusive thrombus

Inflamedthrombus

Arterial wall

Acute and chronic inflammation

Lumen

Inflammatory thrombus

Thrombus center

Possible neutrophilic microabscesses

Evolution

Organization and recanalization

Original schematic — not histology

Slide 16 · Microabscesses are within the thrombus

Characteristic thrombi may contain small aggregates of neutrophils.

Granulomatous inflammation can surround these microabscesses.

Vessel-wall inflammatory cells coexist with the intraluminal lesion.

This morphology is illustrated figure but not reproduced here.

Distinguish thrombus-associated microabscesses from a generic mural inflammatory infiltrate.

Slide 17 · Thrombus evolution can change the lumen

Acute occlusivethrombus

Inflammatoryorganization

Partialrecanalization

Persistent perfusionimpairment

Recanalization does not imply full restoration of distal vascular function.

Slide 18 · Buerger uniquely extends beyond arteries

Inflammatory neurovascular unit

Artery +thrombus

Vein

Nerve

Inflammation extendsto veins and nerves

Later fibrosis mayencase all three

Original simplified schematic — not histology

Slide 19 · Nerve involvement helps explain disproportionate pain

Arterialinsufficiency

Extension of inflammationto nearby nerves

Ischemic + neuralinjury

Severe restpain

The source explicitly links unusually intense pain to neural involvement.

Slide 20 · Early clues in Buerger disease

Raynaud phenomenon may precede fixed tissue injury.

Instep claudication causes exertional foot pain.

Superficial nodular phlebitis can accompany arterial disease.

These findings suggest disease in distal neurovascular territories.

An early symptom complex is not the same as established gangrene.

Slide 21 · Late tissue injury in Buerger disease

Recurrent distalischemia

Pain at restand impaired healing

Chronic digital /extremity ulceration

Gangrene

The lesion evolves from reversible symptoms toward structural tissue loss.

Slide 22 · Smoking abstinence: Stage matters

Early course

Abstinence may ameliorate further attacks

Prevents continued smoke-related exposure

Established lesions

Fixed vascular injury may persist despite abstinence

Cessation is not equivalent to reversal of organized lesions

Slide 23 · Buerger: Integrated phenotype

Exposure

Heavy cigarette smoking is the main epidemiologic association.

Anatomy

Distal limb arteries; Associated superficial veins and nerves.

Outcome

Occlusion produces claudication, rest pain, ulcers, gangrene.

This vascular-neural-thrombotic pattern distinguishes it from systemic visceral PAN.

Slide 24 · Clinical application: Distal ischemia

A young heavy cigarette smoker develops exercise-induced instep pain, painful digits, and recurrent superficial nodular phlebitis. Subsequent symptoms include severe pain at rest.

Which disease and which vascular relationships best account for the presentation?

Slide 25 · Case resolution: Distal thromboangiitis

Most consistent entity: Thromboangiitis obliterans (Buerger disease).

Distal muscular artery thrombosis accounts for ischemic claudication.

Inflammation extending into veins explains nodular phlebitis.

Adjacent nerve involvement contributes to severe pain.

No single symptom establishes the diagnosis; The pattern is the teaching point.

Slide 26 · PAN: Systemic necrotizing muscular arteritis

Polyarteritis nodosa (PAN) affects small- to medium-sized muscular arteries.

It preferentially involves renal and visceral arterial beds.

The pulmonary circulation is characteristically spared.

Clinical injury results from ischemia and infarction of supplied organs.

PAN is an arterial disease; It does not classically target glomerular capillaries.

Slide 27 · PAN has an organ-selective distribution

Affected muscular arteries

Kidney

Renal arteries → hypertension

Heart

Coronary branches → ischemia

Liver

Hepatic arterial involvement

Gastrointestinal tract

Pain / hemorrhagic injury

Peripheral nerves

Neuritis, often motor

Muscle

Diffuse myalgia

Slide 28 · A subset of PAN is associated with hepatitis B

Chronic hepatitis Bin a subset

HBsAg–antibodyimmune complexes

Vasculardeposition

Necrotizingarteritis

The textbook estimates an HBV association in approximately one-third; This is not presented as a contemporary population estimate.

Slide 29 · Most PAN cases are not explained by HBV

The source links roughly one-third of PAN cases to chronic hepatitis B.

It describes the cause in remaining patients as unknown.

An immune-complex model explains the HBV-associated subset.

Avoid assigning that specific trigger to every PAN patient.

Etiologic heterogeneity is compatible with a recognizable arterial lesion.

Slide 30 · PAN is not an ANCA-associated vasculitis

PAN (Robbins)

No association with antineutrophil cytoplasmic antibodies

Predominantly muscular arteries

No classic glomerular capillaritis

ANCA-associated small-vessel group

PR3-ANCA and MPO-ANCA patterns are important

Often involves arterioles or capillaries

Glomerulonephritis and pulmonary capillaritis may occur

Slide 31 · The PAN lesion is segmental and transmural

Thrombus

Segmental

Only part of artery circumference may be involved

Transmural

Inflammatory injury crosses the wall

Necrotizing

Fibrinoid necrosis in active disease

Luminal

Thrombosis may coexist

Original schematic — not histology

Slide 32 · PAN often targets arterial branch points

Lesions favor arterial branches and may involve only part of a wall

Focal wall injury

Segmental arterial involvement

Schematic arterial tree, not angiography

Slide 33 · Active PAN: A mixed inflammatory infiltrate

Acute lesions show transmural arterial inflammation.

Neutrophils, eosinophils and mononuclear cells may coexist.

Fibrinoid necrosis is a frequent accompaniment.

Lumen thrombosis adds an immediate flow-limiting component.

Slide 34 · Fibrinoid necrosis signals destructive wall injury

Acute transmuralinflammation

Fibrinoidwall necrosis

Vessel wallweakening

Aneurysm and/orthrombosis

Fibrinoid necrosis denotes wall destruction, not simply a thrombus.

Slide 35 · Multiple lesion ages coexist in PAN

Active lesions

Leukocyte-rich inflammation

Fibrinoid necrosis

Possible thrombotic occlusion

Healed / older lesions

Fibrous thickening extends toward adventitia

Remodeling and persistent stenosis

Different stages may coexist in one organ

Slide 36 · Downstream injury depends on perfusion loss

Reduced flow

Ischemic atrophy when perfusion remains chronically insufficient.

Abrupt occlusion

Infarcts and focal ulcerations after severe arterial compromise.

Wall disruption

Hemorrhage may accompany destructive arteritis or aneurysm.

The pathologic consequences follow directly from arterial geometry and injury.

Slide 37 · Renal PAN: Arterial injury → hypertension

Renal arteryvasculitis

Reduced renalperfusion

Acceleratinghypertension

Major clinicalcomplication

The renal-artery pattern is distinct from primary glomerular capillaritis.

Slide 38 · Gastrointestinal PAN: Ischemic abdominal illness

Visceral musculararteritis

Intestinal vascularinsufficiency

Abdominalpain

Mucosal injury andbloody stools

Pain and gastrointestinal bleeding may reflect the same ischemic mechanism.

Slide 39 · PAN can cause peripheral neuritis

Peripheral nerves are vulnerable to ischemia from affected feeding arteries.

Peripheral neuritis is a typical presentation.

The motor component is described as predominant.

Coexisting myalgias and visceral symptoms suggest systemic arterial involvement.

Slide 40 · PAN can remit and relapse

Clinical disease can be episodic, with symptom-free intervals.

Different vascular territories may be affected at different times.

Mixed-age lesions provide a morphologic counterpart to continued injury.

An unremarkable interval does not erase the structural arterial damage.

Slide 41 · PAN severity derives from vital-organ ischemia

Organ threat

Renal involvement: Important contributor to mortality

Visceral disease: Ischemic bowel injury

Cardiac disease: Arterial ischemia

Source-reported outcome

Untreated PAN is commonly fatal account

Immunosuppression substantially improves survival

Up to 80% five-year survival with treatment

Slide 42 · PAN versus microscopic polyangiitis

Discriminator

Polyarteritis nodosa

Microscopic polyangiitis

Primary vessel pattern

Medium / small muscular arteries

Small vessels incl. capillaries

Glomerular involvement

No classic glomerular vasculitis

Necrotizing glomerulonephritis common

Pulmonary circulation

Usually spared

Pulmonary capillaritis may occur

ANCAs

No association

Often MPO-ANCA

Slide 43 · PAN diagnostic reasoning starts with distribution

Systemic ischemicfeatures

Renal + gastrointestinalor nerve findings

Muscular-arterynecrotizing pattern

Consider PAN; Distinguishsmall-vessel disease

This is a teaching pathway, not formal diagnostic or classification criteria.

Slide 44 · Clinical application: Visceral and renal ischemia

A young adult develops rapidly accelerating hypertension, abdominal pain with bloody stools, diffuse myalgias, and motor-predominant peripheral neuritis.

Which vasculitis pattern and vascular lesions best unite these findings?

Slide 45 · Case resolution: Polyarteritis nodosa

The combination favors systemic PAN.

Renal muscular-artery lesions explain hypertension.

Visceral ischemia accounts for pain and bloody stools.

Necrotizing, segmental arteritis may produce thrombosis, aneurysm and infarction.

A multisystem ischemic syndrome can have a unifying arterial origin.

Slide 46 · Kawasaki disease: Childhood medium-vessel arteritis

An acute febrile illness, generally of infancy and childhood.

80% of patients are younger than five years.

Large- to medium-sized arteries may be involved.

Coronary arteritis determines much of the clinical importance.

The dominant threat is coronary rather than renal or distal-limb ischemia.

Slide 47 · A coronary-centered vascular phenotype

Affected muscular arteries

Coronary arteries

Arteritis and wall injury

Coronary aneurysm

Focal arterial dilation

Coronary thrombosis

Luminal occlusion

Myocardium

Potential infarction

Cardiovascular outcome

Occasional sudden death

Healed arteries

Obstructive intimal thickening

Slide 48 · Kawasaki etiology remains incompletely resolved

A trigger following infection is proposed, often framed as viral.

Host genetic susceptibility is considered relevant.

Immune cross-reactivity as a candidate mechanism.

This hypothesis is not an identified single infectious cause.

Slide 49 · Proposed immune sequence in Kawasaki disease

Susceptiblehost + trigger

Cross-reactive /new antigens

Cytokines + polyclonalB-cell activation

Antibodies to ECsand SMCs

This is the mechanism proposed by Robbins, not an established universal pathway.

Slide 50 · Kawasaki histology is transmural

Narrowed lumen

Wall injury

Arteritis

Dense transmural inflammatory infiltrate

Necrosis

Often less fibrinoid necrosis than in PAN

Wall integrity

Injury permits aneurysm formation

Healing

Obstructive intimal thickening may remain

Original schematic — not histology

Slide 51 · PAN and Kawasaki share an arterial injury pattern

Feature

PAN

Kawasaki disease

Inflammation

Segmental transmural necrotizing

Dense transmural inflammatory

Fibrinoid necrosis

Common in active lesions

Usually less conspicuous

Aneurysms

May accompany thrombosis

Major coronary complication

Clinical context

Systemic visceral / renal

Febrile childhood syndrome

Slide 52 · Kawasaki coronary aneurysms: Mechanism

Coronaryarteritis

Inflammatory injuryto vessel wall

Arterialdilatation

Aneurysm with risk ofthrombosis / rupture

Coronary arterial inflammation can persist as a mechanical vascular hazard.

Slide 53 · Healed Kawasaki lesions may obstruct flow

Acute arteryinflammation

Clinicalresolution

Healing withintimal thickening

Residual coronarystenosis

Self-limited fever does not guarantee normalization of the affected artery.

Slide 54 · Mucocutaneous lymph node syndrome

Mucosal / ocular

Conjunctival and oral erythema; Oral mucosal changes.

Extremities / skin

Edema of hands and feet; Palm/sole redness; Desquamating rash.

Lymph nodes

Cervical lymph-node enlargement in a febrile child.

The clinical grouping provides a clue to possible coronary risk.

Slide 55 · Extremity findings evolve with the illness

Early inflammatory signs

Hand and foot edema

Erythema of palms and soles

Subsequent epithelial change

Desquamating rash

Cutaneous changes accompany systemic fever

Slide 56 · Coronary complications explain major morbidity

Ectasia / aneurysm

Loss of normal coronary caliber after inflammatory wall injury.

Thrombotic occlusion

Intraluminal clot can compromise myocardial perfusion.

Myocardial damage

Infarction or sudden death can follow severe coronary involvement.

Slide 57 · Untreated coronary sequelae are not rare

The source estimates cardiovascular sequelae in approximately 20% of untreated patients.

The spectrum includes clinically silent coronary arteritis and coronary ectasia.

Large coronary aneurysms can rupture or thrombose.

These textbook figures describe an untreated cohort, not treated contemporary rates.

Slide 58 · Therapy changes Kawasaki coronary outcomes

Recognize childhoodsyndrome

Intravenousimmunoglobulin

Aspirin in thesource regimen

Marked reduction in symptomaticcoronary artery disease

Therapeutic statement reflects Robbins; No dose or contemporary guideline is inferred.

Slide 59 · Kawasaki-like MIS-C: Related description, not identity

Textbook observation

A Kawasaki-like inflammatory syndrome has been described after SARS-CoV-2 infection

Term used: Multisystem inflammatory syndrome in children (MIS-C)

Interpretive boundary

Phenotypic similarity does not prove identical disease mechanisms

Do not substitute MIS-C diagnostic criteria for Kawasaki disease

Slide 60 · Clinical application: Febrile mucocutaneous syndrome

A preschool child develops fever, conjunctival and oral erythema, swelling of hands and feet, erythematous palms and soles, desquamation, and cervical lymphadenopathy.

Which artery group makes this clinical syndrome especially important?

Slide 61 · Case resolution: Evaluate the coronary risk

The constellation is characteristic of Kawasaki disease in the source.

Coronary arterial inflammation is the central pathology concern.

Wall damage can create aneurysms with thrombosis or rupture.

Intravenous immunoglobulin with aspirin reduces symptomatic coronary complications.

Slide 62 · Three diseases: Three dominant modes of damage

Question

Buerger

PAN

Kawasaki

Who / context?

Young heavy smoker

Systemic presentation

Febrile young child

Where?

Distal limb vessels

Visceral / renal arteries

Coronary arteries

Dominant lesion?

Inflamed thrombus

Necrotizing arteritis

Transmural arteritis

Primary tissue threat?

Gangrene

Organ infarction

Myocardial infarction

Slide 63 · Matching an artery to its clinical signal

Distal extremity

Claudication + rest pain + superficial phlebitis suggest Buerger.

Renal and visceral

Hypertension + bowel ischemic symptoms suggest PAN.

Coronary in childhood

Mucocutaneous fever + coronary hazard suggest Kawasaki.

Distribution carries more discriminating information than inflammation alone.

Slide 64 · A source-based reasoning pathway

Identify clinicalcontext

Locate dominantarterial territory

Determine lesion:Thrombus / necrosis / aneurysm

Compare withthree disease patterns

Schematic reasoning aid, not a validated diagnostic algorithm.

Slide 65 · Avoid common category mistakes

Medium-vessel diseases can affect arteries outside the nominal size class.

PAN should not be treated as equivalent to ANCA-associated capillaritis.

Kawasaki and PAN share transmural inflammation but differ in clinical setting and coronary predilection.

Buerger disease affects associated nerves and veins; It is not simply distal atherosclerosis.

Slide 66 · Lesion morphology at a glance

Morphologic question

Buerger disease

PAN

Kawasaki disease

Is thrombosis prominent?

Yes: inflamed, often occlusive

May accompany necrosis

Possible in damaged coronary arteries

Is fibrinoid necrosis central?

Not the defining feature

Characteristic in active lesions

Less prominent than PAN

Can vessel damage cause aneurysm?

Not emphasized in source

Yes

Yes, especially coronary

Can healed lesions narrow lumen?

Organized thrombus

Fibrous wall thickening

Obstructive intimal thickening

Slide 67 · Interpretations must separate evidence levels

Established in supplied source

Three principal diseases within medium-vessel group

Characteristic vessel distribution and morphology

Textbook clinical complications and treatment effects

Not established by available files

Current external guideline algorithms or new classifications

Modern incidence, trial estimates or cohort-specific rates

Authentic microscopy images or licensed textbook figure reproductions

Slide 68 · Integration exercise: Three short presentations

Presentation

Most likely disorder

Reason

Smoker; instep claudication + phlebitis

Buerger

Distal vascular-neural syndrome

Hypertension; bloody stools + neuritis

PAN

Systemic visceral + renal ischemia

Febrile child; oral + extremity findings

Kawasaki

Mucocutaneous syndrome; coronary hazard

Slide 69 · Final synthesis: Phenotype reflects vessel injury

Buerger: Tobacco-associated thrombosing inflammation of distal limb neurovascular bundles.

PAN: Segmental necrotizing muscular-artery injury with systemic ischemic consequences.

Kawasaki: Childhood transmural arteritis with potentially serious coronary aneurysms.

Classify by pattern; Explain presentations through vascular anatomy and morphology.

Identify the artery → understand the lesion → predict the organ at risk.

Slide 70 · Primary source and scope

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026).

Chapter 11, Blood Vessels: vasculitis and medium-vessel vasculitis, printed pp. 463–468.

Classification context: Table 11.4; morphology captions: Figs. 11.22, 11.25 and 11.26.

Figures not reproduced: original Chapter 11 PDF and authenticated image assets were not supplied.