Small Vessel Vasculitis

Slide 1 · Small Vessel Vasculitis

Pathogenesis • morphology • clinicopathologic recognition

Immune-complex and ANCA-associated disorders

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify small-vessel vasculitis by vascular immune deposits.

Explain immune-complex and ANCA-mediated injury to small vessels.

Recognize diagnostic morphology and characteristic organ involvement.

Differentiate microscopic polyangiitis, GPA, EGPA and major immune-deposit disorders.

Slide 3 · The vascular compartment defines the disease

Small artery / arteriole

Capillary bed

Postcapillary venule

SCHEMATIC — NOT HISTOLOGY

Most commonly affected: Small intraparenchymal arteries, arterioles, capillaries and venules.

Medium-sized arteries may also participate; Vessel caliber is a predominance, not an absolute boundary.

Organ manifestations reflect the vascular beds injured.

Slide 4 · Two patterns of small-vessel immunopathology

Immune-deposit pattern

Ig and/or complement depositsOften associated with immune-complex GN

Pauci-immune pattern

Few or no deposits in most lesionsStrong association with ANCAs

Immune-complex disease: Vessel walls contain appreciable immunoglobulin and/or complement.

ANCA-associated disease: Necrotizing injury with few detectable immune deposits (pauci-immune).

Similar clinical and H&E appearances can arise by different mechanisms.

Slide 5 · Vasculitis is vessel-wall inflammation

Inflammatory wall injury

Reduced integrity / lumen

Ischemia or hemorrhage

Inflammatory destruction can narrow or occlude the lumen.

Vessel-wall injury can produce tissue hemorrhage, ischemia or thrombosis.

Constitutional symptoms may coexist with focal, organ-specific effects.

SCHEMATIC

Slide 6 · Mechanisms must be distinguished before treatment

Direct infectious injury

Vascular invasion by pathogenAddress underlying infection

Noninfectious immune injury

Autoantibodies, complexes or T cellsMechanism guides therapy

Immune-mediated inflammation is a major cause of noninfectious vasculitis.

Microorganisms can also invade vessels directly or trigger indirect immune injury.

Immunosuppression can help immune vasculitis but may harm uncontrolled infection.

Slide 7 · Why renal and pulmonary beds matter

Kidney

Glomerular capillary injury

Hematuria / proteinuria

Lung

Alveolar capillary injury

Hemorrhage / hemoptysis

Glomerular capillaries can undergo necrotizing glomerulonephritis.

Pulmonary capillaries can develop capillaritis and alveolar hemorrhage.

Concurrent hematuria and hemoptysis therefore suggest potentially severe small-vessel injury.

Slide 8 · Immune deposits organize the differential

Vascular injury

Evaluate deposit pattern

Integrate organs + serology

Marked immune deposits favor immune-complex or antibody-mediated pathways.

Sparse deposits support a pauci-immune mechanism in an appropriate clinicopathologic context.

Leukocytoclastic change alone does not distinguish these categories.

SCHEMATIC

Slide 9 · Immune complexes initiate a vascular injury cascade

Antigen–antibody complexes

Complement / Fc activation

Vessel-wall inflammation

Circulating complexes may deposit in vessel walls; Complexes may also arise locally.

The responsible antigen is often not identified.

Complement activation and Fc-receptor-bearing leukocytes propagate damage.

SCHEMATIC

Slide 10 · Immune-complex formation: Two possible locations

Preformed complexes

Circulate before vascular deposition

In-situ complexes

Antibody encounters antigen at tissue site

Circulating antigen–antibody complexes can become trapped in vessel walls.

Alternatively, complexes may form in situ after local antigen binding.

The relative importance of these routes often remains uncertain.

Slide 11 · Complement amplifies immune-complex injury

Wall immune deposits

Complement activation

Inflammatory recruitment

Tissue injury

Vessel-wall antibody and/or complement deposition is detectable in lesional tissue.

Complement activation recruits and activates inflammatory effector cells.

The recruited inflammatory cells then damage the vascular wall.

SCHEMATIC

Slide 12 · Fc-receptor-bearing cells are central effectors

Immune deposits

Fc-receptor cells

Endothelial damage

Neutrophils bind antibody-containing complexes through Fc receptors.

Monocytes and macrophages can contribute to vascular inflammation.

Endothelial injury reflects activated inflammatory-cell interactions.

SCHEMATIC

Slide 13 · Immune-deposit vasculitis: Diagnostic tissue logic

Routine morphology

What kind of vessel injury exists?

Immunodeposit evaluation

What immune material remains in the lesion?

H&E identifies inflammatory vascular injury; Immunostaining evaluates the deposited material.

Significant wall Ig and/or complement supports an immune-deposit pathway.

Immune-complex glomerulonephritis is a common associated renal pattern.

Slide 14 · Drug hypersensitivity can form immune complexes

Drug-linked / foreign antigen

Specific antibody

Immune complexes

Vascular injury

Some drugs act as haptens after binding serum proteins (textbook example: Penicillin).

Some agents are foreign proteins themselves (textbook example: Streptokinase).

Antibodies then recognize these antigens and promote immune-complex formation.

SCHEMATIC

Slide 15 · Drug-associated vasculitis: Clinical priority

Exposure

Review drugs and timing

Seek a plausible trigger

Course

Disease can vary in severity

Removal may permit resolution

Skin lesions are the most frequent clinical manifestations.

The course ranges from mild self-limited disease to severe systemic illness.

Recognizing and withdrawing the offending agent is often decisive.

Slide 16 · Infection may trigger indirect immune-complex injury

Microbial antigen

Antibody response

Immune complexes

Vascular lesion

Antibodies directed against microbial constituents can form circulating immune complexes.

Complexes may lodge in vascular walls and activate inflammatory pathways.

This indirect mechanism differs from direct microbial invasion of a vessel.

SCHEMATIC

Slide 17 · Hepatitis B illustrates the immune-complex bridge

Mechanism

HBV antigen–antibody complexes

Disease category

PAN: Predominantly medium-arterial vasculitis

A subset of polyarteritis nodosa (PAN) to HBsAg–anti-HBsAg complexes.

PAN remains classified under medium-vessel vasculitis, despite involving small arteries.

The example illustrates immune-complex pathogenesis, not reclassification of PAN as a small-vessel vasculitis.

Slide 18 · Autoimmune disorders can produce vasculitis

SLE

Multiple autoantibodies

DNA–anti-DNA complexes highlighted

Rheumatoid arthritis

Long-standing severe disease

Small/medium-vessel vasculitis

Systemic lupus erythematosus, rheumatoid arthritis and antiphospholipid antibody syndrome are examples.

Autoantibodies may provide substrates for vascular immune-complex formation.

Some disorders have additional cell-mediated or antiendothelial contributions.

Slide 19 · Systemic lupus erythematosus: Multiple complexes

Autoantigen + antibody

Vascular immune deposition

Vasculitis

DNA–anti-DNA complexes are prominent candidates in SLE-associated vascular injury.

Other autoantibodies may also contribute to vasculitis.

SLE may affect small and medium-sized vessels.

SCHEMATIC

Slide 20 · Rheumatoid vasculitis has a specific context

Typically occurs with long-standing, severe rheumatoid arthritis.

May involve both small and medium-sized vessels.

Antiendothelial antibodies and cell-mediated immunity may also participate.

Slide 21 · IgA vasculitis: A distinctive immune-complex substrate

Abnormally glycosylated IgA

IgG-containing complexes

Small-vessel deposition

IgA vasculitis was previously termed Henoch–Schönlein purpura.

Robbins implicates IgG complexes with abnormally glycosylated IgA.

It belongs to the immune-deposit subgroup of small-vessel vasculitis.

SCHEMATIC

Slide 22 · Cryoglobulinemic vasculitis: Deposit-related injury

Cryoglobulin-containing Ig

Vascular deposits

Inflammatory injury

Cryoglobulins are immunoglobulins that precipitate when cooled.

Cryoglobulin immune deposits are implicated in vascular inflammation.

Its placement within immune-deposit vasculitis reflects immunoglobulin deposition.

SCHEMATIC

Slide 23 · Anti-GBM disease: Direct antibody binding

Anti-GBM autoantibody

Basement membrane binding

Complement / leukocytes

Capillary injury

Autoantibodies directly recognize components of glomerular and pulmonary capillary basement membranes.

This is direct antibody binding rather than circulating immune-complex deposition.

Complement and leukocyte-mediated damage can be similar to immune-complex vasculitis.

SCHEMATIC

Slide 24 · Anti-GBM and immune complexes are not identical

Immune complexes

Antigen–antibody complexesDeposited or formed in situ

Anti-GBM antibody

Direct tissue-antigen bindingGlomerular + pulmonary membranes

Both mechanisms may leave substantial immunoglobulin in involved tissue.

Immune complexes reflect antigen–antibody complexes; Anti-GBM antibody binds basement membrane directly.

Mechanistic interpretation requires immunostaining pattern plus clinical context.

Slide 25 · ANCA targets are neutrophil-associated antigens

PR3-ANCA

Historically associated with c-ANCA labeling

MPO-ANCA

Historically associated with p-ANCA labeling

ANCAs react with constituents of neutrophil primary granules and related cell compartments.

The principal antigen-specific categories are proteinase 3 (PR3) and myeloperoxidase (MPO).

Antigen specificity is more useful than historical staining labels alone.

Slide 26 · PR3-ANCA has a strong GPA association

PR3 target antigen

PR3-directed ANCA

GPA association

Proteinase 3 is an enzyme in neutrophil azurophilic granules.

Microbial peptide homology as one possible explanation for PR3 autoimmunity.

PR3-ANCA is particularly associated with granulomatosis with polyangiitis.

SCHEMATIC

Slide 27 · MPO-ANCA links several phenotypes

MPO granule protein

MPO-ANCA

MPA / subset of EGPA

Myeloperoxidase is a granule enzyme involved in reactive oxygen species production.

MPO-ANCA commonly accompanies microscopic polyangiitis.

It is also found in a subset of EGPA; Some therapeutic agents can induce it.

SCHEMATIC

Slide 28 · Intracellular antigens can become accessible

Leukocyte activation

PR3 / MPO exposure

ANCA binding

ANCA antigens are principally intracellular in resting neutrophils.

Low-level surface expression or surface translocation occurs during activation or apoptosis.

Circulating ANCAs can then engage their targets on leukocytes.

SCHEMATIC

Slide 29 · How ANCAs promote pauci-immune vascular injury

ANCA–neutrophil binding

ROS + proteases

Endothelial injury

ANCA engagement can directly activate neutrophils.

Activated cells release reactive oxygen species and proteolytic enzymes.

Inflammatory-cell interactions with endothelium cause destructive vascular injury.

SCHEMATIC

Slide 30 · Pauci-immune does not mean nonimmune

Systemic immune driver

Circulating autoantibody activating cells

Local tissue appearance

Few detectable immune deposits despite injury

ANCA autoantibodies target cellular proteins rather than forming typical deposited immune complexes.

Lesions therefore usually contain few demonstrable antibodies or complement deposits.

Profound necrotizing inflammation can coexist with weak or absent tissue immunodeposits.

Slide 31 · Three principal ANCA-associated syndromes

Entity

Defining tissue emphasis

Microscopic polyangiitis

Necrotizing small-vessel lesions; no granulomas

Granulomatosis with polyangiitis

Respiratory granulomas; necrotizing vasculitis

Eosinophilic GPA

Eosinophils and granulomas; asthma association

Slide 32 · ANCA results require clinicopathologic integration

Clinical phenotype

Serologic specificity

Tissue morphology

Integrated diagnosis

ANCAs as useful diagnostic and disease-activity markers.

However, disease recognition also depends on affected organs and morphology.

The hallmark is a coherent constellation—not the antibody result alone.

SCHEMATIC

Slide 33 · Microscopic polyangiitis: Disease definition

Capillary

Arteriole

Venule

SCHEMATIC — NOT HISTOLOGY

Necrotizing vasculitis of capillaries, arterioles and venules.

Medium-sized and large arterial involvement is not the dominant pattern.

MPO-ANCA is associated with most cases; Deposits are generally sparse.

Slide 34 · Microscopic polyangiitis affects multiple beds

Kidney

Necrotizing glomerulonephritis

Hematuria / proteinuria

Lung

Pulmonary capillaritis

Hemoptysis

Skin, mucosa, lung, kidney, muscle, gastrointestinal tract and other organs may be involved.

Necrotizing glomerulonephritis and pulmonary capillaritis are especially important.

Vascular distribution accounts for the diversity of presenting symptoms.

Slide 35 · MPA morphology: Segmental necrotizing injury

Segmental media injury

Fibrinoid necrosis

Transmural extension

SCHEMATIC — NOT HISTOLOGY

A segment of the media develops fibrinoid necrosis.

Transmural necrotizing foci may also occur.

Granulomatous inflammation is absent in classic MPA.

Slide 36 · Leukocytoclastic vasculitis is a pattern

Neutrophil infiltration

Nuclear fragmentation

Wall damage

SCHEMATIC — NOT HISTOLOGY

Neutrophils infiltrate and fragment, especially in postcapillary venules.

Fragments of neutrophil nuclei produce leukocytoclasis.

The same pattern may accompany immune-complex vasculitis; It is not ANCA-specific.

Slide 37 · MPA-associated renal injury

Glomerular capillary inflammation

Necrotizing injury

Hematuria / proteinuria

Necrotizing glomerulonephritis is very common’ description.

Capillary damage disrupts the glomerular filtration barrier.

Hematuria and proteinuria are resulting clinical manifestations.

SCHEMATIC

Slide 38 · MPA pulmonary capillaritis

Alveolar capillaritis

Barrier disruption

Pulmonary hemorrhage

Alveolar capillaries are vulnerable to necrotizing inflammation.

Damage to capillary walls can produce alveolar hemorrhage.

Hemoptysis signals clinically significant pulmonary involvement.

SCHEMATIC

Slide 39 · The pulmonary–renal MPA pattern

Lung

Capillary inflammatory injury

Hemoptysis

Kidney

Necrotizing capillary injury

Hematuria

Simultaneous glomerular and pulmonary capillary injury provides a unifying mechanism.

Respiratory hemorrhage plus urinary blood/protein should raise concern for systemic small-vessel injury.

The pattern is not uniquely diagnostic of MPA; GPA and anti-GBM disease may also affect these organs.

Slide 40 · MPA can follow environmental or drug triggers

The source cites hydralazine as a potential drug trigger.

Certain infections, including Staphylococcus aureus, are also discussed as possible triggers.

Trigger recognition must not replace tissue and clinical assessment.

Slide 41 · MPA versus polyarteritis nodosa

Feature

MPA

PAN

Main vessels

Capillaries, venules, arterioles

Small/medium arteries

Glomerular inflammation

Characteristic

Absent by classification

Pulmonary capillaritis

May occur

Not typical

Lesion age

Often similar

May be mixed

Slide 42 · MPA clinical findings follow organ injury

Skin

Postcapillary small vessels

Palpable purpura

Viscera

Renal / lung / bowel beds

Organ-specific symptoms

Palpable purpura reflects cutaneous small-vessel injury.

Hematuria/proteinuria, hemoptysis, abdominal pain/bleeding and myalgias may occur.

Widespread renal or CNS involvement can produce major morbidity.

Slide 43 · MPA treatment response reflects immune activity

Durable remission is possible with immunosuppression in many patients.

Recognition and removal of a suspected inciting exposure is important.

Extent of renal or neurologic injury strongly influences clinical seriousness.

Slide 44 · GPA is defined by a triad of lesions

Airways

Necrotizing granulomas

Upper or lower tract

Kidney

Necrotizing glomeruli

Crescents may form

Necrotizing granulomatous inflammation of upper and/or lower respiratory tract.

Necrotizing or granulomatous vasculitis of small to medium-sized vessels.

Focal necrotizing, often crescentic, glomerulonephritis.

Slide 45 · Upper-airway GPA: Granulomatous inflammation

Airway inflammation

Granulomas / necrosis

Sinusitis and ulceration

Granulomatous sinusitis is a classic upper-tract lesion.

Nasal, palatal or pharyngeal ulceration may result from tissue destruction.

Respiratory tract disease can precede or occur without generalized organ injury.

SCHEMATIC

Slide 46 · Pulmonary GPA can form nodules and cavities

Granulomatous lesions

Coalescence / necrosis

Nodules ± cavitation

Lung lesions range from diffuse infiltrates to granulomatous nodules.

Coalescing necrotizing granulomas may produce cavitating masses.

Alveolar hemorrhage may coexist with parenchymal destructive inflammation.

SCHEMATIC

Slide 47 · GPA granulomas are a major discriminator

GPA

Necrotizing granulomatous inflammation

MPA

Necrotizing vasculitis without granulomas

Epithelioid histiocytes and giant cells may occur adjacent to inflamed vessels.

Destructive necrotizing granulomatous parenchymal inflammation can be extensive.

Granulomatous lesions distinguish GPA from classic MPA.

Slide 48 · GPA vessel lesions involve adjacent parenchyma

Vascular / tissue necrosis

Fibroblastic response

Organization / fibrosis

Necrotizing inflammation can involve vessel walls and surrounding tissue.

A fibroblastic response may accompany granulomatous lesions.

Healing may progress toward organization and fibrosis.

SCHEMATIC

Slide 49 · GPA renal pathology can progress to crescents

Capillary loop necrosis

Parietal-cell response

Glomerular crescent

Early renal lesions can show focal, segmental glomerular capillary necrosis.

More extensive injury may provoke parietal epithelial-cell proliferation.

The resulting crescentic glomerulonephritis marks severe glomerular injury.

SCHEMATIC

Slide 50 · GPA pathogenesis involves cellular immunity

Inhaled trigger hypothesis

T-cell response

Granulomatous inflammation

An abnormal T-cell-mediated response to inhaled environmental or microbial antigens.

Granuloma formation is consistent with a cellular inflammatory component.

PR3-ANCA-mediated neutrophil activation provides an additional pathogenic pathway.

SCHEMATIC

Slide 51 · PR3-ANCA is particularly informative in GPA

Strongly associated with GPA.

Antibody measurements may contribute to monitoring but must be interpreted alongside clinical findings.

The respiratory granuloma / renal lesion combination remains the defining clinicopathologic clue.

Slide 52 · GPA ranges from limited to systemic disease

Localized phenotype

Upper/lower respiratory injury predominates

Systemic phenotype

Respiratory + kidney / other organs

Limited disease may remain restricted to the respiratory tract.

Disseminated disease may involve eyes, skin, cardiac tissue and other organs.

Renal disease is an important contributor to systemic severity.

Slide 53 · GPA clinical recognition is multisystem

Upper airway

Chronic sinusitis / ulcers

Granulomatous injury

Lower airway

Nodules / cavitation

Necrotizing lesions

Chronic sinusitis or destructive upper-airway disease is a major clue.

Pulmonary infiltrates, nodules or cavities add a lower-airway clue.

Urinary abnormalities suggest associated necrotizing glomerulonephritis.

Slide 54 · Untreated GPA is dangerous but treatable

High mortality for untreated classical systemic GPA.

Immunosuppression has transformed disease into a relapsing-remitting course for many patients.

Residual fibrosis and organ damage may persist despite control of activity.

Slide 55 · EGPA links eosinophilia, allergy and vasculitis

Asthma / allergic background

Eosinophilic inflammation

Granulomatous vasculitis

Classically associated with asthma and allergic rhinitis.

Peripheral eosinophilia and eosinophilic tissue infiltrates are characteristic.

Necrotizing granulomatous inflammation can affect small to medium-sized vessels.

SCHEMATIC

Slide 56 · Eosinophil-rich granulomas distinguish EGPA

EGPA

Eosinophil-rich lesions + granulomas

MPA

Necrotizing vessels; Granulomas absent

Extravascular necrotizing granulomas are described in EGPA.

Eosinophils infiltrate blood vessels and other tissues.

Both eosinophils and granulomas help distinguish EGPA from MPA.

Slide 57 · EGPA respiratory phenotype

Upper respiratory

Allergic rhinitis

Allergic inflammatory setting

Lower respiratory

Asthma / infiltrates

Eosinophilic tissue disease

Asthma is a central clinical association.

Allergic rhinitis and pulmonary infiltrates are common elements of the classical syndrome.

Extravascular granulomas can accompany respiratory inflammation.

Slide 58 · EGPA cardiac involvement is consequential

Myocardial eosinophils

Cytotoxic tissue injury

Cardiomyopathy

Eosinophilic myocardial infiltrates can damage cardiac myocytes.

Resultant cardiomyopathy is an important cause of morbidity and death.

Cardiac dysfunction in an eosinophilic vasculitic phenotype warrants particular attention.

SCHEMATIC

Slide 59 · EGPA can affect skin, gut and kidneys

Skin

Small-vessel involvement

Purpura

Other organs

Gastrointestinal / renal

Bleeding or renal signs

Palpable purpura reflects cutaneous vascular involvement.

Gastrointestinal bleeding is a recognized association.

Renal disease occurs, but the dominant clinical picture may be asthma/eosinophilic organ injury.

Slide 60 · ANCA is not universal in EGPA

ANCA-positive subset

MPO reactivity often observed

ANCA-negative subset

Asthma + eosinophilic tissue disease remains relevant

Only a subset of EGPA patients has MPO-ANCA, unlike the stronger association of MPA with MPO-ANCA.

ANCA as more frequent with concurrent renal involvement.

ANCA negativity does not exclude the classical eosinophilic granulomatous phenotype.

Slide 61 · MPA, GPA and EGPA: Morphologic contrasts

Finding

MPA

GPA

EGPA

Granulomas

Absent

Present

Present

Eosinophilic lesions

Not defining

Not defining

Characteristic

Respiratory pattern

Capillaritis

Necrotizing nodules / airways

Asthma / infiltrates

Typical ANCA

MPO

PR3

MPO in subset

Renal injury

Frequent GN

Necrotizing/crescentic GN

Variable

Slide 62 · Behçet syndrome is a variable-vessel disorder

Small-vessel classification

Defined chiefly by vessel caliber and deposit pattern

Behçet syndrome

Variable-vessel inflammatory syndrome

Behçet syndrome adjacent to the small-vessel vasculitides.

It can involve both veins and arteries rather than a single vessel-caliber compartment.

The defining recognition pattern is multisystem inflammatory disease.

Slide 63 · Behçet mucosal disease offers a clinical clue

Oral mucosa

Transient ulcers

Common recurrent feature

Genital / skin

Ulcers and variable skin lesions

Multisystem disease

Recurrent, self-healing oral ulcers occur in almost all cases.

Genital ulcers can be larger and persist longer.

Skin and articular involvement are also frequently seen.

Slide 64 · Behçet vascular and neurologic complications

Eye / CNS

Uveitis; Brainstem inflammation

Vision / neurologic injury

Vascular system

Venous thrombosis; Aneurysms

Thrombotic / aneurysmal complications

Ocular involvement may include uveitis or hypopyon.

Venous thrombosis, arterial aneurysms and retinal vascular inflammation are described.

Central nervous system lesions, particularly in the brainstem, can cause persistent injury.

Slide 65 · Behçet disease: Immune hypothesis and tissue

Genetic susceptibility

Unidentified trigger

Th17-linked injury

The initiating cause is not established account.

Genetic susceptibility involving Th17 response regulation and environmental triggers are proposed.

Some skin biopsies show leukocytoclastic inflammation with mixed inflammatory cells.

SCHEMATIC

Slide 66 · Start diagnosis with the vessel injury pattern

Vessel + histology

Immune deposits

PR3 / MPO context

Organ pattern

Identify the involved compartment: Venules/capillaries versus muscular arteries.

Characterize necrosis, neutrophil fragmentation, granulomas and eosinophils.

Then integrate tissue immune deposits, serum ANCA specificity and organ phenotype.

SCHEMATIC

Slide 67 · Immune deposits change the interpretation

Immune-positive lesion

Consider IgA, cryoglobulins, SLE, drug/infection, anti-GBM

Pauci-immune lesion

Consider MPA, GPA or EGPA phenotype

Abundant immune material favors immune-complex or direct antibody-binding mechanisms.

Pauci-immune necrotizing injury is characteristic of ANCA-associated syndromes.

No single staining result replaces an integrated clinicopathologic diagnosis.

Slide 68 · Clinical phenotype guides targeted tissue review

Presentation clue

Pathology question

Cavitating respiratory nodules

Is there necrotizing granulomatous vasculitis?

Asthma + eosinophilia

Are eosinophil-rich granulomas present?

Pulmonary–renal injury

Is necrotizing capillaritis / GN present?

Purpura with deposits

What immune material is deposited?

Slide 69 · Case: Hemoptysis, hematuria and purpura

An adult develops hemoptysis and urinary blood with palpable purpura.

A vessel biopsy shows segmental necrosis and neutrophilic fragments.

No granulomas are seen; Tissue immune deposits are minimal.

Question: Which small-vessel syndrome best fits the combination?

TRACE THE CLUES

Lung capillaritis

Renal capillary injury

Pauci-immune pattern

Slide 70 · Case interpretation: Microscopic polyangiitis

Pulmonary + renal injury

No granulomas

Pauci-immune pattern

MPA favored

The pulmonary–renal syndrome is compatible with MPA.

Absence of granulomas separates this pattern from classical GPA.

MPO-ANCA supports the pattern, but renal/lung evaluation remains decisive.

SCHEMATIC

Slide 71 · Case: Chronic sinusitis and cavitating nodules

Persistent sinonasal disease is followed by cavitating pulmonary nodules.

Tissue shows necrotizing granulomatous inflammation involving small vessels.

Urinary blood raises concern for associated glomerular disease.

Question: Identify the unifying syndrome and its most associated ANCA.

TRACE THE CLUES

Upper airway

Lower airway

Kidney

Slide 72 · Case interpretation: GPA and PR3-ANCA

Respiratory granulomas

Necrotizing vasculitis

Glomerulonephritis

GPA favored

Respiratory necrotizing granulomas and small-vessel vasculitis favor GPA.

Focal necrotizing or crescentic glomerulonephritis completes the classic triad.

PR3-ANCA is the characteristic antigen association.

SCHEMATIC

Slide 73 · Case: Asthma with eosinophilic organ injury

An individual with asthma and allergic rhinitis develops peripheral eosinophilia.

Tissue shows eosinophil-rich inflammation and necrotizing granulomas.

New cardiac dysfunction raises concern for eosinophilic myocardial injury.

Question: Which vasculitis unifies these observations?

TRACE THE CLUES

Asthma

Eosinophilia / granulomas

Cardiac injury

Slide 74 · Case interpretation: EGPA

Allergic respiratory illness

Eosinophilic granulomas

Systemic vasculitis

EGPA favored

Asthma and eosinophil-rich granulomatous vasculitis strongly support EGPA.

Myocardial infiltration explains possible cardiomyopathy.

MPO-ANCA may be present but is not required for recognition of the phenotype.

SCHEMATIC

Slide 75 · Case: Palpable purpura after a new exposure

Palpable purpura appears after a newly introduced medication.

Small-vessel inflammation shows appreciable immunoglobulin/complement deposits.

Question: Is a deposited immune-complex pathway or pauci-immune ANCA mechanism more consistent?

TRACE THE CLUES

Drug exposure

Vascular immune deposits

Immune-deposit mechanism

Slide 76 · Case interpretation: Drug-linked immune complexes

Medication antigen

Immune complexes

Vascular damage

Remove trigger

A drug-related immune-complex process fits the deposited immune material.

Consider a drug hapten or other antigenic exposure as.

Identifying and discontinuing the culprit medication can permit resolution.

SCHEMATIC

Slide 77 · Mechanisms and morphology: Final synthesis

Immune-deposit disease involves vessel-wall antibody/complement accumulation and leukocyte activation.

ANCA disease causes necrotizing injury through leukocyte activation with few tissue deposits.

Granulomas, eosinophils, glomerular lesions and respiratory phenotype distinguish the ANCA syndromes.

Always distinguish immune injury from direct infection and interpret results in organ context.

Slide 78 · Primary source and scope

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

Blood Vessels: Vasculitis and Small Vessel Vasculitis.

The discussion of immune complexes and ANCAs is developed within the same textbook section.

Related mechanisms: immune-mediated injury and glomerular basement membrane autoantibodies.