Vasculitis

Slide 1 · Pathology lecture

Vasculitis

Vessel-wall injury, classification, morphology and clinicopathologic patterns

Inflammatory vascular injury · major patterns · clinical correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain why vessel-wall inflammation produces ischemia, thrombosis, aneurysm and systemic symptoms.

Distinguish infectious invasion from immune-mediated vasculitis.

Classify major noninfectious forms by vessel caliber and immunopathogenesis.

Recognize defining morphologic and clinical patterns of representative vasculitides.

Slide 3 · Vasculitis is inflammation of the vessel wall

The defining lesion is inflammation within the vascular wall—not merely inflammation around a vessel.

Presentations reflect the vascular territories damaged.

Disease may remain localized to one organ or be systemic across several vascular beds.

General inflammatory symptoms often coexist with organ-specific injury.

Slide 4 · Local versus systemic distribution

Single-organ pattern

A vascular bed in one tissue is principally affected

Limited at presentation does not establish lifelong localization

Systemic pattern

Several organ vascular beds are involved

Constitutional symptoms and multiple organ syndromes may coexist

The anatomic distribution explains why one umbrella term contains clinically dissimilar diseases.

Slide 5 · Constitutional manifestations reflect inflammation

Fever and malaise are manifestations of systemic inflammatory activity.

Myalgias and arthralgias may accompany vessel-wall injury.

Absence of striking systemic symptoms does not exclude an organ-threatening localized process.

Specific manifestations depend on whether perfusion, vascular integrity or both are compromised.

Slide 6 · Inflammation connects the vessel lesion to organ injury

Wall inflammation

Luminal narrowing / thrombosis

Reduced downstream perfusion

Ischemic organ injury

Necrotizing arteritis can also weaken the vessel wall, producing aneurysm or rupture.

Slide 7 · Four clinically important consequences

Stenosis

Wall thickening reduces luminal diameter

Pulse deficits; Tissue hypoperfusion

Thrombosis

Endothelial injury promotes occlusion

Infarction; Organ dysfunction

Aneurysm

Inflammation weakens the wall

Risk of rupture or local thrombosis

Hemorrhage

Disruption of vessel integrity

Tissue or alveolar bleeding

Slide 8 · First etiologic branch: Infection or immunity?

Inflamed vessel wall

Direct microbial invasion OR immune injury

Different underlying mechanisms

Different therapeutic implications

Infection can also trigger a secondary immune-mediated vasculitis; Categories are not mutually exclusive.

Slide 9 · Why identifying infection matters

Immunosuppression is appropriate for some immune-mediated processes.

The same intervention may worsen vasculitis caused by an invasive pathogen.

Microbes may damage a vessel directly or trigger immune complexes without invading the wall.

Physical injury, irradiation and toxins are additional causes of vascular inflammation.

Slide 10 · Direct microbial invasion: Typical settings

Bacteria such as Pseudomonas may invade arterial walls.

Fungi including Aspergillus and Mucor species can be angioinvasive.

Spread can occur locally from infected tissue or abscesses.

Less commonly, hematogenous seeding follows septicemia or infected emboli from endocarditis.

Slide 11 · Direct infection can cause two distinct complications

Microbial vessel-wall invasion

Destructive arteritis

Wall weakening OR thrombosis

Aneurysm OR downstream infarction

Example: Meningeal vessel thrombosis during bacterial meningitis can contribute to brain infarction.

Slide 12 · Direct infectious versus secondary immune vasculitis

Question

Direct infectious vasculitis

Infection-triggered immune vasculitis

Where is the injury initiated?

Pathogen invades vascular wall

Antigen–antibody response injures wall

Illustrative mechanism

Fungal or bacterial angioinvasion

Circulating microbial immune complexes

Important distinction

Treat invasive infection

Establish immunologic mechanism

Clinical hazard

Thrombosis; infected aneurysm

Systemic immune-mediated injury

The presence of infection in a patient is not proof of direct microbial vascular invasion.

Slide 13 · Classifying noninfectious vasculitis

Vessel caliber: Large, medium or small is the first organizing principle.

Tissue preference and distribution provide additional discrimination.

Immune deposits, autoantibodies and granulomas refine classification.

Overlap is common; An affected artery does not always fit its nominal caliber category.

Slide 14 · Vessel caliber predicts the broad clinical pattern

Large

Aorta and its major branches

Aortic and great-vessel disease

Medium

Major visceral arteries and branches

Aneurysms, stenoses, regional ischemia

Small

Arterioles, capillaries and venules

Skin, lung capillary and renal glomerular injury

Size categories describe predominant—not exclusive—vascular involvement.

Slide 15 · Large-, medium- and small-vessel overview

Predominant caliber

Representative entities

Typical vessel-level consequence

Large

Giant cell arteritis; Takayasu arteritis

Great-vessel narrowing or wall damage

Medium

Buerger disease; PAN; Kawasaki disease

Arterial thrombosis or aneurysm

Small

MPA; GPA; EGPA; immune-complex forms

Capillaritis; glomerulonephritis; purpura

The entity lists are representative, not exhaustive.

Slide 16 · Classification has important overlap

Giant cell arteritis can affect arteries smaller than the aorta.

Medium-vessel diseases can involve small arteries and branch vessels.

Small-vessel vasculitis may also involve medium-sized arteries.

Distribution, serology and pathology must be integrated rather than treating caliber as an absolute rule.

Slide 17 · Four immune pathways recur across vasculitides

Immune complexes

Deposits recruit complement and inflammatory cells

Vessel-wall deposits may be demonstrable

ANCA antibodies

Neutrophil activation leads to proteolytic vascular injury

Typically pauci-immune vessels

Anti-endothelial antibodies

May contribute to vascular inflammatory targeting

Implicated in selected entities

Autoreactive T cells

T-cell/cytokine pathways foster granulomatous arteritis

Prominent in large-vessel disorders

Slide 18 · Immune-complex vasculitis: Injury cascade

Antigen–antibody deposits

Complement / Fc receptor activation

Neutrophil and monocyte recruitment

Vessel-wall injury

The responsible antigen is often unidentified; Complexes may arrive via blood or form locally.

Slide 19 · Immune deposits are a major diagnostic discriminator

Immune-complex forms show moderate or extensive immunoglobulin and/or complement deposition.

Immune-complex glomerulonephritis often accompanies the vascular lesions.

ANCA-associated forms generally lack conspicuous tissue immunoglobulin deposits.

Patterns of deposition help distinguish mechanisms, but must be interpreted with lesion age.

Slide 20 · Anti-GBM disease: Antibody binds in situ

Anti-basement membrane antibody

Direct binding in glomerular / pulmonary capillaries

Complement and leukocyte injury

Renal and pulmonary injury

Unlike classic deposited immune complexes, the antibody reacts directly with structural basement-membrane targets.

Slide 21 · ANCA antigens: Use target specificity

Antibody

Main target

Robbins-linked patterns

PR3-ANCA

Proteinase 3 in neutrophil granules

Granulomatosis with polyangiitis

MPO-ANCA

Myeloperoxidase in granules

Microscopic polyangiitis; eosinophilic GPA

Legacy staining

c-ANCA / p-ANCA patterns

Target-specific nomenclature is preferred

Association is not disease identity: Serology must be interpreted with clinicopathologic findings.

Slide 22 · ANCA-mediated neutrophil injury

Primed / activated neutrophil

PR3 or MPO appears on cell surface

ANCA binding activates cell

Oxidants and enzymes damage endothelium

ANCAs target primarily intracellular antigens that can become accessible on activated cells.

Slide 23 · Why ANCA-associated lesions are pauci-immune

Antibodies bind neutrophil antigens rather than forming classic circulating immune complexes.

Vessel wall may be necrotic despite few demonstrable antibody or complement deposits.

PR3/MPO antibody testing supports diagnosis, but is not a substitute for tissue/clinical correlation.

Clinical severity and relapse risk may track with antibody activity, but are not inferred from a single result.

Slide 24 · Granulomatous versus nongranulomatous injury

Pattern

Morphologic clue

Representative contexts

Granulomatous arteritis

Macrophages ± giant cells near injured wall

GCA; Takayasu arteritis

Necrotizing vasculitis

Fibrinoid wall necrosis with inflammation

PAN; MPA

Granulomatous necrosis

Necrotizing respiratory granulomas

GPA

Eosinophil-rich lesions

Eosinophils with necrotizing granulomas

EGPA

Morphology overlaps and may be incomplete in limited specimens.

Slide 25 · Schematic: Inflammatory stenosis

Narrowed lumen

Wall inflammation and intimal thickening diminish the open lumen.

Less flow to dependent tissue explains ischemic manifestations.

SCHEMATIC

Original editable cross-section; Not a histologic specimen or to scale.

Slide 26 · Schematic: Destructive vessel injury

Wall damage / remodeling

Transmural injury can destroy structural support and permit aneurysmal dilation.

Thrombosis may coexist with inflammatory arterial wall damage.

SCHEMATIC

Original conceptual drawing; Not an anatomic measurement or clinical image.

Slide 27 · Segmental lesions create sampling pitfalls

Giant cell arteritis often has skip lesions along the same artery.

PAN typically affects only part of an arterial circumference.

Multiple stages of PAN injury may occur in different vessel segments.

The location and length of biopsy determine which part of the disease is actually seen.

Slide 28 · Link the vascular bed to symptoms

Cranial arteries

Temporal headache; Ophthalmic ischemia

Visual loss in GCA

Aortic branches

Pulse or pressure asymmetry

Takayasu arteritis

Visceral arteries

Abdominal pain; Hypertension

PAN

Glomerular / lung capillaries

Hematuria; Hemoptysis

Small-vessel vasculitis

Slide 29 · A rational pathology-based approach

Establish evidence of inflammation involving a vascular wall.

Determine predominant caliber, anatomic territories and lesion pattern.

Assess for immune deposits and ANCA-associated or granulomatous features.

Search for infectious context before attributing the lesion to autoimmunity.

Slide 30 · Histology requires pattern recognition, not one finding

Fibrinoid necrosis establishes destructive injury but is not specific to a single vasculitis.

Neutrophil fragmentation (leukocytoclasia) occurs in several small-vessel mechanisms.

Granulomas and giant cells can be focal or absent in a limited biopsy.

Active inflammation, healed scarring and vascular remodeling may coexist.

Slide 31 · Large-vessel arteritis: Shared phenotype

Giant cell arteritis and Takayasu arteritis are principal large-vessel forms.

Both can produce granulomatous inflammation and chronic arterial wall remodeling.

Aorta and major branches are especially relevant; Medium arteries may also be affected.

Clinical age and distribution often distinguish entities whose histology overlaps.

Slide 32 · Giant cell arteritis: Characteristic distribution

Chronic arteritis, often granulomatous, commonly targets cranial arterial branches.

Temporal arteries are accessible for biopsy but are not uniquely susceptible.

The aorta, carotid/vertebral branches and ophthalmic circulation can be involved.

Often occurs after age 50 and threatens visual function.

Slide 33 · Giant cell arteritis: Proposed immune mechanism

Unidentified arterial-wall antigen

T-cell activation; IFN-γ / IL-17 pathways

Macrophages and granulomatous inflammation

Elastic injury and intimal growth

This mechanism is described as likely, not definitively established; Tissue tropism remains unexplained.

Slide 34 · Giant cell arteritis: Wall remodeling

Narrowed lumen

Granulomatous inflammation commonly centers on the internal elastic lamina.

Elastic fragmentation and intimal thickening accompany luminal compromise.

Healed lesions may show wall scarring and adventitial fibrosis.

SCHEMATIC

Editable conceptual cross-section; Assess real morphology on authentic histology.

Slide 35 · Giant cell arteritis: Skip lesions

Inflammation is discontinuous along a potentially involved artery.

Adequate biopsy sampling improves the chance of detecting a diagnostic focus.

Multinucleated giant cells are useful but not obligatory in each specimen.

A negative biopsy does not definitively exclude GCA when the clinical syndrome is compelling.

Slide 36 · Giant cell arteritis: Clinical pattern

Systemic

Fatigue; Fever; Weight loss

Inflammation may precede focal complaints

Cranial

New headache; Facial pain; Tender temporal artery

Cranial arterial inflammation

Ocular

Diplopia or abrupt vision loss

Ophthalmic vascular involvement

Possible permanent blindness makes ocular involvement an urgent clinical concern.

Slide 37 · GCA: Ophthalmic injury is the critical complication

Temporal disease may coexist with vertebral and ophthalmic artery involvement.

Visual symptoms can develop abruptly and permanent vision loss can follow.

Do not use a negative limited biopsy to dismiss a strongly supported clinical syndrome.

Prompt evaluation and treatment are emphasized by Robbins because ischemic blindness may be irreversible.

Slide 38 · Takayasu arteritis: Clinical identity

Granulomatous arteritis of aorta and major branches, often presenting before age 50.

The aortic arch and great vessels are especially prone to severe narrowing.

Markedly weak upper-extremity pulses explain the term “pulseless disease.”

Immune-mediated T-cell mechanisms are considered likely.

Slide 39 · Takayasu arteritis: Aortic-branch stenosis

Narrowed lumen

Transmural fibrous thickening and intimal hyperplasia narrow large arteries.

Arch branch obstruction explains asymmetric or diminished upper-extremity pulses.

SCHEMATIC

Illustrative cross-section of stenosis; Not an angiogram.

Slide 40 · Takayasu: Inflammation becomes fibrosis

Early lesions can include adventitial mononuclear inflammation near vasa vasorum.

Medial infiltrates and granulomatous inflammation may include giant cells.

Chronic lesions scar across intima, media and adventitia.

Aortic root involvement occasionally produces dilation and aortic valve insufficiency.

Slide 41 · Takayasu: Organ consequences of branch disease

Upper limbs

Weak pulses; Reduced blood pressure

Great-vessel stenosis

Brain / eyes

Neurologic deficits; Visual problems

Cranial circulation compromise

Renal vessels

Systemic hypertension

Renal arterial narrowing

Coronary / pulmonary

Myocardial ischemia; Pulmonary hypertension

Relevant ostial or pulmonary arterial involvement

Slide 42 · Giant cell arteritis versus Takayasu arteritis

Characteristic

Giant cell arteritis

Takayasu arteritis

Age profile

Usually >50 years

Usually <50 years

Emphasized vessels

Cranial arteries ± aorta

Aortic arch and major branches

Clinical clue

Headache; potential vision loss

Weak pulses; pressure asymmetry

Histology

Often granulomatous

Often granulomatous; may overlap

Age patterns guide classification but are not histologic diagnostic criteria.

Slide 43 · Medium-vessel arteritis: Recurring pathology

Predominantly involves muscular arteries and their branches.

Consequences include arterial stenosis, thrombosis, infarction or aneurysm.

Three major Robbins examples are Buerger disease, polyarteritis nodosa and Kawasaki disease.

The disease-specific distribution and host context are diagnostically informative.

Slide 44 · Buerger disease: Segmental thrombosing vasculitis

Thromboangiitis obliterans targets distal medium arteries, especially tibial and radial arteries.

Acute and chronic inflammation accompanies luminal thrombosis.

Classically affects young individuals with heavy tobacco exposure.

Reduced distal perfusion explains acral ischemia and tissue injury.

Slide 45 · Buerger disease: Tobacco-linked vascular injury

Tobacco exposure

Direct endothelial toxicity OR immune reaction

Segmental arteritis with thrombosis

Distal limb ischemia

The source presents competing mechanistic explanations; Neither is conclusively established.

Slide 46 · Buerger disease: Signature morphology

Occlusive thrombi may contain neutrophilic microabscesses.

Granulomatous inflammation surrounds intrathrombotic microabscesses.

Adjacent veins and peripheral nerves may participate in the inflammatory process.

Organization, recanalization and fibrosis may occur in longstanding lesions.

Slide 47 · Buerger disease: Ischemic and neural symptoms

Vasospasm

Raynaud phenomenon

Often an early complaint

Claudication

Exercise-induced instep foot pain

Distal perfusion failure

Neural pain

Severe rest pain

Associated nerve involvement

Tissue loss

Ulcers or gangrene

Progressive ischemia

The value of early smoking abstinence in limiting further attacks.

Slide 48 · Polyarteritis nodosa: Distribution is decisive

PAN is a systemic necrotizing arteritis of medium and small muscular arteries.

Renal and visceral arterial beds are prominent targets.

Pulmonary arterial circulation and glomerular capillaries are characteristically spared.

ANCA association is absent in classic PAN; Hepatitis B immune complexes may contribute in some patients.

Slide 49 · PAN: Segmental transmural necrotizing injury

Wall damage / remodeling

Transmural inflammation and fibrinoid necrosis affect segments of the arterial wall.

Thrombus and aneurysm may complicate structurally injured segments.

Part of the wall circumference may remain uninvolved.

SCHEMATIC

Original editable arterial lesion schematic, not a histologic image.

Slide 50 · PAN: Lesions of different ages coexist

Active lesions contain mixed inflammatory cells with fibrinoid necrosis and sometimes thrombus.

Healing lesions show fibrous wall thickening extending into the adventitia.

Active and healed lesions may occur in neighboring vessels.

A branch-point predilection and segmental involvement contribute to uneven perfusion.

Slide 51 · PAN: Clinicopathologic consequences

Renal arteries

Accelerating hypertension

Ischemia rather than primary glomerulitis

Mesenteric arteries

Abdominal pain; Bloody stools

Intestinal vascular injury

Peripheral nerves

Motor-predominant neuropathic deficits

Vasa nervorum injury

Muscle

Diffuse myalgias

Muscular arterial involvement

Slide 52 · PAN versus microscopic polyangiitis

Feature

PAN

MPA

Vessel caliber

Small and medium arteries

Arterioles, capillaries, venules

Glomerular involvement

Glomerular capillaries spared

Necrotizing GN frequent

Pulmonary capillaritis

Not characteristic

Common

ANCA association

Not associated

Often MPO-ANCA

Lesion chronology

Mixed stages coexist

Lesions often same age

These are discriminating patterns, not an exhaustive diagnostic rule set.

Slide 53 · Kawasaki disease: An acute childhood arteritis

Febrile systemic illness largely affecting infants and young children.

Mucocutaneous inflammation and cervical lymphadenopathy are characteristic.

Medium- and large-artery involvement can include coronary arteries.

In susceptible hosts, infection-triggered immune responses are proposed, not proven as a single cause.

Slide 54 · Kawasaki coronary injury: A causal sequence

Coronary arteritis

Wall damage and remodeling

Coronary aneurysm / narrowing

Thrombosis or ischemic infarction

Coronary complications, rather than noncardiac vascular findings, drive much of its clinical significance.

Slide 55 · Kawasaki disease: Wall changes

Dense transmural inflammation can resemble the arteritis of PAN.

Fibrinoid necrosis tends to be less prominent than in PAN.

Arterial injury may leave aneurysmal dilation or healed obstructive intimal lesions.

That treatment reduces clinically important coronary sequelae.

Slide 56 · Kawasaki disease: Mucocutaneous syndrome

Conjunctival and oral erythema accompany fever.

Hands and feet may be edematous, with palmar or plantar erythema.

Desquamating rash and cervical lymph node enlargement are characteristic.

Coronary artery complications range from ectasia to aneurysm and thrombosis.

Slide 57 · Small-vessel vasculitis: An immunologic split

Capillaries, venules, arterioles and intraparenchymal small arteries predominate.

Immune-complex disease generally has vessel-wall antibody and complement deposits.

ANCA-associated disease is characteristically pauci-immune.

Both mechanisms may produce glomerular or pulmonary microvascular lesions.

Slide 58 · Small-vessel vasculitis: Deposition pattern

Assessment

Immune-complex pattern

ANCA-associated pattern

Tissue immunoglobulin

Moderate to extensive deposits

Few or no deposits

Complement injury

Frequently contributes

Antibody activation of neutrophils

Common organs

Skin; kidney; systemic beds

Kidney; lung; skin and others

Example

IgA/cryoglobulinemic vasculitis

MPA; GPA; EGPA

Direct anti-GBM binding is mechanistically distinct despite immunoglobulin deposition.

Slide 59 · Drug-triggered immune-complex vasculitis

A drug may act as a hapten bound to an endogenous carrier protein.

Foreign therapeutic proteins can themselves be antigenic.

Antigen–antibody complexes recruit inflammatory cells to small vessels.

Cutaneous lesions are common; Removing the offending agent is an important etiologic intervention.

Slide 60 · Infection can cause vasculitis without invading the wall

Microbial antigens

Circulating antigen–antibody complexes

Deposition in vessel walls

Complement-mediated inflammation

Hepatitis B surface antigen–antibody complexes are a Robbins example linked to a subset of PAN.

Slide 61 · Systemic autoimmune diseases may inflame vessels

Systemic lupus erythematosus can generate DNA/anti-DNA immune complexes.

Rheumatoid vasculitis tends to occur in longstanding severe rheumatoid arthritis.

Anti-endothelial antibodies and cellular mechanisms may coexist with immune complexes.

The context of systemic disease helps interpret vascular lesions.

Slide 62 · IgA and cryoglobulinemic vasculitis

Entity

Immunologic basis described in Robbins

Interpretive anchor

IgA vasculitis

Complexes involving abnormally glycosylated IgA

Small-vessel immune-complex injury

Cryoglobulinemic vasculitis

Immunoglobulins that precipitate below body temperature

Vascular immune deposits

Common implication

Vessel-wall Ig/complement deposition

Look for systemic associations

Subclassification and test interpretation extend beyond this introductory pathology comparison.

Slide 63 · Anti-GBM disease has direct antigen binding

Autoantibodies recognize glomerular and pulmonary capillary basement membranes.

Unlike circulating antigen–antibody immune complexes, binding is directly to target basement membrane.

Complement activation and leukocyte injury can nevertheless resemble other antibody-mediated disease.

Kidney and lung involvement follows the anatomic distribution of the antigen.

Slide 64 · Microscopic polyangiitis: Phenotype

MPA is a necrotizing vasculitis dominated by small vessels.

Necrotizing glomerulonephritis and pulmonary capillaritis are prominent.

MPO-ANCA association is common, while immune deposits are usually sparse.

Many different organ vascular beds may be involved.

Slide 65 · MPA: Histology and leukocytoclasia

Segmental fibrinoid necrosis occurs in capillary-scale and small arterial vessels.

Granulomatous inflammation is absent in its typical morphology.

Fragmented neutrophil nuclei may create a leukocytoclastic pattern.

Leukocytoclasia is not specific: Immune-complex vasculitis can look similar.

Slide 66 · MPA: Small vessels, multisystem symptoms

Lung

Hemoptysis

Pulmonary capillaritis

Kidney

Hematuria; Proteinuria

Glomerular injury

Skin

Palpable purpura

Superficial small-vessel inflammation

Other organs

Bowel symptoms; Weakness

Variable microvascular territories

Slide 67 · GPA: Three interlocking lesions

Respiratory granulomas

Necrotizing lesions in upper and/or lower airways

Sinonasal and lung abnormalities

Necrotizing vasculitis

Small- to medium-sized vessels

Systemic vascular injury

Glomerulonephritis

Focal necrosis often with crescents

Renal disease

Limited disease may initially be restricted to the respiratory tract.

Slide 68 · GPA: Upper airway and lung morphology

Upper airway lesions may show granulomatous sinusitis or mucosal ulceration.

Lung involvement may produce nodules or cavitating granulomatous lesions.

Multifocal necrotizing granulomatous vasculitis can be accompanied by alveolar hemorrhage.

Organizing lesions may progressively fibrose.

Slide 69 · GPA glomerular injury progresses in severity

Focal glomerular capillary necrosis

Capillary loop injury / thrombosis

Parietal epithelial proliferation

Crescentic glomerulonephritis

This is a conceptual severity sequence, not a required temporal pathway in every patient.

Slide 70 · GPA: Serology complements morphology

PR3-ANCA is strongly associated with GPA in the supplied Robbins description.

Granulomatous respiratory pathology and necrotizing glomerulonephritis remain central to recognition.

A single positive antibody result does not by itself establish the full disease phenotype.

The source connects antibody activity with treatment response and disease recurrence.

Slide 71 · EGPA: Asthma, eosinophilia and vasculitis

Eosinophilic granulomatosis with polyangiitis is a necrotizing vasculitis of small vessels.

Asthma, allergic rhinitis and pulmonary infiltrates are common contexts.

Peripheral eosinophilia accompanies eosinophil-rich vascular and extravascular lesions.

Extravascular necrotizing granulomas distinguish the classic morphology.

Slide 72 · EGPA contrasted with other ANCA vasculitides

Characteristic

MPA

GPA

EGPA

Granulomas

Absent

Necrotizing

Eosinophil-rich

Respiratory pattern

Capillaritis

Granulomatous nodules

Asthma / allergic disease

Serologic link

MPO-ANCA

PR3-ANCA

MPO-ANCA in a subset

Organ clue

Renal + lung

Airways + kidney

Cardiac eosinophilic injury

Neither ANCA positivity nor one histologic feature substitutes for the full phenotype.

Slide 73 · EGPA: Systemic injury beyond the airway

Purpura, gastrointestinal bleeding and renal abnormalities can occur.

Eosinophil-rich myocardial inflammation can damage cardiac muscle.

Cardiomyopathy is a major clinical risk in the Robbins account.

The combination of eosinophils and granulomas is a particularly useful morphologic clue.

Slide 74 · Behçet syndrome affects arteries and veins

Multisystem inflammatory disease may cause vasculitis in both arterial and venous beds.

Recurrent oral ulcers, often with genital ulcers, are prominent clinical clues.

Vascular involvement may include arterial aneurysm and venous thrombosis.

The precise trigger is unknown; Abnormal Th17-associated immune responses are proposed.

Slide 75 · Behçet syndrome: Organ manifestations

Mucosa

Recurrent oral ± genital ulcers

Common distinguishing clue

Eye

Uveitis or hypopyon

Threatens ocular function

Central nervous system

Inflammatory brainstem lesions

Potentially severe deficits

Vascular

Aneurysm or venous thrombosis

Both arteries and veins involved

Slide 76 · Integrated comparison: Major arterial vasculitides

Disease

Distinguishing setting

Prominent injury

Giant cell arteritis

Older adult; headache/vision complaint

Cranial arterial granulomatous injury

Takayasu

Younger patient; weak pulses

Aortic branch stenosis

Buerger

Heavy tobacco exposure; distal symptoms

Thrombosing limb arteritis

PAN

Systemic visceral and renal arteries

Necrotizing arteritis; infarction

Kawasaki

Febrile mucocutaneous childhood illness

Coronary arteritis / aneurysm

This comparison is a diagnostic orientation, not a formal classification score.

Slide 77 · Integrated comparison: Small-vessel entities

Entity

Immunopathology

Distinguishing clue

Immune-complex vasculitis

Ig / complement deposits

Drugs, infection, autoimmunity, IgA

Microscopic polyangiitis

Pauci-immune; MPO-linked

Necrotizing GN; capillaritis

Granulomatosis with polyangiitis

Pauci-immune; PR3-linked

Necrotizing respiratory granulomas

Eosinophilic GPA

Pauci-immune subset; eosinophils

Asthma; eosinophilic granulomas

Anti-GBM disease

Direct basement membrane binding

Glomerular and pulmonary capillaries

Use morphologic and clinical distribution in addition to the immunologic category.

Slide 78 · Five discriminators before labeling a vasculitis

Is the mechanism direct infection, immune injury or physical/chemical damage?

Which vessel caliber and organ distribution predominate?

Is injury granulomatous, necrotizing, eosinophil-rich or thrombosing?

Do tissue deposits support an immune-complex process or pauci-immune injury?

Does the clinical pattern align with available serology and tissue findings?

Slide 79 · Clinical application: New headache and visual symptoms

CLINICAL STEM

An older adult develops new temporal headache and abrupt visual disturbance. Arterial biopsy samples a short segment and shows no giant cells.

Interpretation: Giant cell arteritis remains a serious possibility.

Cranial distribution and vision risk support urgent assessment; Skip lesions and occasional absence of giant cells limit the exclusionary value of one biopsy.

Slide 80 · Clinical application: A pulmonary–renal presentation

CLINICAL STEM

A patient has hemoptysis, hematuria and necrotizing glomerular injury. Tissue shows little immunoglobulin deposition; Respiratory granulomas are not demonstrated.

Interpretation: Consider an ANCA-associated pauci-immune small-vessel vasculitis.

The pulmonary–renal distribution and pauci-immune pattern support the group. MPA versus GPA requires the rest of the clinical, morphologic and serologic phenotype.

Slide 81 · Clinical application: Painful ischemic toes

CLINICAL STEM

A young heavy smoker develops severe distal rest pain, superficial thrombophlebitis and ischemic toe ulcers.

Interpretation: Thromboangiitis obliterans (Buerger disease) is an important consideration.

Tobacco association, distal thrombosing disease and associated venous/neural involvement produce the characteristic clinicopathologic pattern.

Slide 82 · Clinical application: Visceral ischemia without GN

CLINICAL STEM

A patient has difficult hypertension, abdominal pain and motor neuropathy; Visceral arterial biopsy shows segmental transmural necrotizing arteritis, but no glomerular capillaritis.

Interpretation: The pattern favors polyarteritis nodosa over MPA.

PAN affects medium/small muscular arteries, whereas the hallmark small-vessel glomerular and lung capillary lesions point toward MPA.

Slide 83 · Synthesis: Mechanism, caliber and morphology

Definition: The common denominator is inflammation within vascular walls.

Etiology: Distinguish direct infection from immune-mediated injury and other triggers.

Anatomy: Caliber and organ distribution determine the dominant clinical syndrome.

Pathology: Immune deposition, granulomas, necrosis and thrombosis separate major patterns.

Integration: Diagnosis requires tissue, clinical context and appropriately interpreted antibodies.

Slide 84 · Primary teaching source

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

Sections: Vasculitis; Infectious and Noninfectious Vasculitis; Large, Medium and Small Vessel Vasculitis.

The schematic drawings and comparison diagrams in this lecture are original, editable teaching constructs—not clinical images.