Explain vasculitis

Reading File

Finding Sources

Searching PubMed

vasculitis classification pathogenesis

Finding Sources

Reading File

Finding Sources

Reading File

Loading Image

Reading File

I now have rich content from multiple authoritative sources. Let me compile the comprehensive answer.

Vasculitis

Vasculitis is a clinicopathologically defined process characterized by inflammation and necrosis of blood vessel walls, leading to narrowing or occlusion of the lumen, aneurysm formation, and impairment of distal organ function. The vasculitides are a heterogeneous group of rare disorders; collectively they span conditions affecting every organ system and every caliber of vessel.

Andrews' Diseases of the Skin, p. 961
Rheumatology 2-Volume Set (Elsevier, 2022), p. 2093

Classification - Vessel Size is the Primary Organizer

The 2012 Revised International Chapel Hill Consensus Conference (CHCC) is the most widely used nomenclature system. Vessels are divided into three main size categories:

Vessel Size	Vessels Involved	Main Diseases
Large	Aorta and main branches	Takayasu arteritis, Giant cell arteritis (GCA)
Medium	Main visceral arteries (renal, mesenteric, coronary)	Polyarteritis nodosa (PAN), Kawasaki disease
Small	Arterioles, capillaries, venules	ANCA-associated (GPA, MPA, EGPA), Immune complex (IgA vasculitis/HSP, cryoglobulinemic, urticarial vasculitis)
Variable	Any vessel	Behçet disease, Cogan syndrome

Small-vessel vasculitis is further subdivided by mechanism:

ANCA-associated (pauci-immune): Granulomatosis with polyangiitis (GPA, formerly Wegener's), Microscopic polyangiitis (MPA), Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)
Immune complex-mediated: IgA vasculitis (Henoch-Schönlein purpura), cryoglobulinemic vasculitis, hypocomplementemic urticarial vasculitis
Washington Manual of Medical Therapeutics, p. 968
Firestein & Kelley's Textbook of Rheumatology, p. 1945

Pathogenesis

Two major immunological mechanisms drive vessel wall injury:

A. Immune Complex-Mediated (e.g., IgA vasculitis, cryoglobulinemic vasculitis)

Circulating antigens (infections, drugs, neoplasms) stimulate antibody formation
Antibody-antigen immune complexes deposit in postcapillary venule walls
Complement activation generates C3a and C5a - potent mast cell degranulators and neutrophil chemoattractants
Mast cell degranulation increases vascular permeability, enhancing immune complex deposition
Adhesion molecules (E-selectin, ICAM-1, VCAM-1) upregulate on endothelium, tethering neutrophils
Neutrophils release proteolytic enzymes (collagenase, elastase) and reactive oxygen species
Membrane attack complex (C5-C9) activates the clotting cascade → thrombosis, necrosis, hemorrhage

B. ANCA-Mediated (pauci-immune; no significant immune complex deposits)

Cytokine priming (e.g., TNF) causes intracellular neutrophil proteins - PR3 (proteinase 3) and MPO (myeloperoxidase) - to translocate to the cell surface
Autoantibodies (ANCAs) form against these surface-expressed antigens
ANCA binding activates neutrophils, increasing their adhesion to vessel walls
Activated neutrophils release reactive oxygen species and toxic mediators → direct vessel wall damage
Impaired neutrophil apoptosis may prolong the window for autoantibody development

Pathogenesis of vasculitis - immune complex-mediated vs. ANCA-mediated mechanisms

Dermatology 2-Volume Set (Elsevier, 5e), p. 506

Clinical Features by Vessel Size

The skin and organ findings correlate tightly with vessel caliber:

Organ System	Small Vessel	Medium Vessel	Large Vessel
Skin	Palpable purpura (hallmark)	Livedo reticularis, subcutaneous nodules	Cyanosis, claudication
Kidney	Hematuria + RBC casts, proteinuria	Hematuria, flank pain, infarct	Hypertension (renal artery stenosis)
GI	GI bleeding	Bowel perforation	Bowel infarction
Nervous	Polyneuropathy	Mononeuritis multiplex, strokes	Strokes, TIA
Lung	Pulmonary capillaritis, hemorrhage	-	-

Palpable purpura is the hallmark of small-vessel (postcapillary venule) disease. Lesions predominate on the lower legs and ankles (gravity-dependent areas). In bedridden patients, the buttocks may be affected.

Leukocytoclastic vasculitis - palpable purpura on both legs with dark red to purple non-blanchable lesions

Leukocytoclastic vasculitis showing classic palpable purpura - Andrews' Diseases of the Skin

Key Individual Diseases

1. Giant Cell Arteritis (GCA) - Large Vessel

Most common systemic vasculitis in people >50 years (median onset age 75); 4x more common in women
Affects the temporal artery and branches of the external carotid
Presents with: temporal headache, jaw claudication (very specific), scalp tenderness, visual loss (ischemic optic neuropathy - an emergency), 40-50% overlap with polymyalgia rheumatica (PMR)
Elevated ESR (often >50 mm/hr) and CRP
Treated with high-dose glucocorticoids (prednisone 1 mg/kg/day) urgently; tocilizumab (IL-6 inhibitor) as steroid-sparing therapy

2. Takayasu Arteritis - Large Vessel

"Pulseless disease" - affects the aorta and its main branches
Most common in Asian women in the third decade of life
Three phases: (1) constitutional symptoms, (2) vessel pain/tenderness (carotidynia), (3) fibrotic/ischemic phase with absent pulses, limb claudication, hypertension, strokes
Treated with glucocorticoids + steroid-sparing agents (methotrexate, azathioprine, anti-TNF, tocilizumab)

3. Polyarteritis Nodosa (PAN) - Medium Vessel

Necrotizing arteritis of medium arteries WITHOUT glomerulonephritis or capillaritis
ANCA-negative; 30% associated with hepatitis B
Features: livedo reticularis, subcutaneous nodules, mononeuritis multiplex, renal infarcts (but NOT glomerulonephritis), mesenteric ischemia
Treatment: glucocorticoids; cyclophosphamide for severe disease

4. ANCA-Associated Vasculitis (AAV) - Small Vessel, Pauci-immune

Granulomatosis with Polyangiitis (GPA) - formerly Wegener's

Classic triad: upper respiratory tract (sinusitis, saddle-nose deformity, subglottic stenosis) + lower respiratory tract (nodules, cavities) + renal disease (crescentic GN)
c-ANCA / PR3-ANCA positive in ~90% of generalized disease

Microscopic Polyangiitis (MPA)

Capillaritis and glomerulonephritis WITHOUT granulomas or upper respiratory involvement
p-ANCA / MPO-ANCA positive
Pulmonary-renal syndrome common

Eosinophilic Granulomatosis with Polyangiitis (EGPA) - formerly Churg-Strauss

Triad: asthma + eosinophilia (>10%) + granulomatous vasculitis
Classic cardiac involvement (eosinophilic cardiomyopathy)
p-ANCA positive in ~50%

2022 ACR/EULAR classification criteria for AAV use weighted scoring systems with >90% sensitivity and specificity - Firestein & Kelley's Rheumatology, p. 1945

5. IgA Vasculitis (Henoch-Schönlein Purpura) - Small Vessel, Immune Complex

Most common vasculitis in children (though adults can be affected)
Classic tetrad: palpable purpura (lower extremities) + arthralgia/arthritis + abdominal pain + renal disease (hematuria, proteinuria)
Defining feature: IgA deposits in vessel walls on immunofluorescence
Usually self-limiting (6-16 weeks); treatment is primarily supportive
Renal prognosis worse in adults than children

Histology

The classic finding in small-vessel vasculitis is leukocytoclastic vasculitis (LCV):

Segmental inflammation of postcapillary venules
Fibrinoid necrosis of vessel walls
Neutrophil infiltration with nuclear fragmentation (karyorrhexis/leukocytoclasia)
Endothelial cell swelling, vascular thrombosis
On immunofluorescence: immunoglobulins, complement, and fibrin in vessel walls (if biopsy taken within 24 hours)
IgA deposits persist longer in IgA vasculitis and are the diagnostic hallmark

Etiology

Category	Examples
Idiopathic	Most cases of cutaneous LCV
Infections	Hepatitis B (PAN), Hepatitis C (cryoglobulinemic vasculitis), HIV, streptococcal infection (IgA vasculitis)
Drugs	Penicillins, sulfonamides, allopurinol, propylthiouracil (drug-induced ANCA vasculitis)
Autoimmune	Rheumatoid arthritis, SLE, Sjögren syndrome
Malignancy	Lymphoreticular malignancies > solid tumors; IgA vasculitis in adults can be malignancy-associated
Genetic	HLA associations; environmental triggers

Diagnosis

Clinical suspicion: systemic symptoms + unexplained organ dysfunction or palpable purpura
Labs: CBC, ESR, CRP, ANCA (c-ANCA/PR3-ANCA, p-ANCA/MPO-ANCA), cryoglobulins, complement (C3, C4), hepatitis serology, ANA, urinalysis
Imaging: CT/MR angiography for large/medium vessel disease; PET scan for active arteritis
Tissue biopsy: Skin (punch biopsy within 24-48 hours), temporal artery, kidney, or lung - to confirm diagnosis and guide classification
2022 ACR/EULAR criteria now available for GPA, MPA, EGPA, GCA, Takayasu, PAN, IgA vasculitis

Treatment Principles

Disease Category	Induction	Maintenance
AAV (GPA, MPA, EGPA)	High-dose glucocorticoids + rituximab or cyclophosphamide	Rituximab or azathioprine; taper steroids
GCA	Prednisone 40-60 mg/day	Tocilizumab (anti-IL-6); slow steroid taper over 12-24 months
Takayasu	Prednisone 1 mg/kg/day	Methotrexate, azathioprine, tocilizumab, anti-TNF agents
PAN	Prednisone ± cyclophosphamide	Steroid taper
IgA vasculitis	Supportive (colchicine, dapsone for skin)	Steroids for GI/renal disease; IVIG for refractory cases
Cutaneous LCV	Remove offending cause (drug, infection)	Usually self-resolving in 3-4 weeks

Summary

Vasculitis is best understood through the lens of vessel size + mechanism:

Large vessel: granulomatous inflammation, ischemic symptoms (GCA, Takayasu)
Medium vessel: necrotizing arteritis causing organ infarction (PAN, Kawasaki)
Small vessel, pauci-immune (ANCA+): direct neutrophil-mediated damage, glomerulonephritis, pulmonary hemorrhage
Small vessel, immune complex: complement-driven inflammation, palpable purpura, IgA deposits (HSP)

The 2022 ACR/EULAR classification criteria (PMID: 38913291) represent the current standard for research classification, though clinical diagnosis requires integrating serology, biopsy, and imaging findings.

This is a shared conversation. Sign in to Orris to start your own chat.