Vasculitis: Large, Medium & Small Vessel - A Complete Guide

The Master Diagram - Chapel Hill Consensus Classification

The Core Framework

Important rule: overlap exists. Medium vessel vasculitis can also hit small arteries, and large vessel vasculitis can involve medium-sized vessels. But the predominant target is what defines the category. - Goldman-Cecil Medicine, p. 2848

LARGE VESSEL VASCULITIS (LVV)

1. Giant Cell Arteritis (GCA) - "Temporal Arteritis"

• Age: >50 years (almost exclusively). More common in women
• Target vessels: Extracranial branches of the aorta, especially temporal artery and other branches of the carotid/vertebral arteries. Spares intracranial vessels
• Pathology: Granulomatous arteritis
• Classic symptoms:
  • New-onset headache (temporal region)
  • Jaw claudication (prandial jaw pain - highly specific)
  • Scalp tenderness
  • Visual loss (ischemic optic neuropathy - an emergency!)
  • Palpable, tender, cord-like thickened temporal artery
• Associated condition: Polymyalgia rheumatica (PMR) - pain and stiffness of neck, shoulders, hips, thighs. About 50% of GCA patients have PMR; ~15% of isolated PMR patients eventually develop GCA
• Diagnosis: Temporal artery biopsy (gold standard)
• Physical signs: Asymmetric pulses, BP discrepancy between arms, bruits

2. Takayasu Arteritis

• Age: <50 years - adolescent girls and young women (2nd-3rd decade), especially from Japan, Southeast Asia, India
• Target vessels: Aorta and major branches (subclavian, carotid, renal arteries)
• Pathology: Granulomatous; cannot be distinguished from GCA by pathology alone - age is the key differentiator
• Classic symptoms:
  • Pulseless disease - absent or weak pulses in upper extremities
  • Discrepant blood pressure between arms
  • Bruits over affected vessels
  • Hypertension (from renal artery involvement)
  • Arm or leg claudication
• Classic presentation: Young non-smoking woman with pulseless extremities and BP discrepancy

MEDIUM VESSEL VASCULITIS (MVV)

1. Polyarteritis Nodosa (PAN)

• Age: Older adults; all genders and races
• Key association: Historically linked to Hepatitis B (now <5% in developed countries due to vaccination; used to be >35%)
• Target vessels: Main visceral arteries especially renal, mesenteric, hepatic, coronary. Also epineural arteries (causing mononeuritis multiplex) and subcutaneous arteries
• Does NOT affect: Lungs (pulmonary vessels spared - key distinguisher from ANCA vasculitis), glomerular capillaries
• Pathology: Necrotizing arteritis - fibrinoid necrosis with neutrophil-rich inflammation, evolves to fibrosis. Segmental involvement at branch points

• Classic symptoms:
  • Fever, weight loss, fatigue
  • Testicular pain (highly specific - testicular artery involvement)
  • Mononeuritis multiplex (foot drop, wrist drop)
  • Hypertension (renovascular)
  • Livedo reticularis, skin nodules
  • Abdominal pain (mesenteric ischemia)
• Classic arteriographic finding: Multiple microaneurysms (1-5 mm) in renal, mesenteric, hepatic arteries
• ANCA negative (important distinguisher from MPA/GPA)

2. Kawasaki Disease

• Age: Children (typically <5 years); Japan and East Asia highest rates
• Pathology: Necrotizing arteritis (similar histology to PAN)
• Classic "CRASH" criteria:
  • Conjunctival injection (bilateral, non-purulent)
  • Rash (polymorphous)
  • Adenopathy (cervical lymphadenopathy >1.5 cm)
  • Strawberry tongue / lip cracking / oral mucositis
  • Hand/foot swelling (edema with desquamation later)
  • • Fever >5 days
• Feared complication: Coronary artery aneurysms (can cause MI even in young children; overall mortality up to 3%)
• Treatment: IVIG + Aspirin (early treatment prevents coronary aneurysms)
• Generally self-limited

SMALL VESSEL VASCULITIS (SVV)

GROUP A: ANCA-Associated Vasculitis (AAV)

• c-ANCA (cytoplasmic pattern) = anti-PR3 antibodies → associated with GPA
• p-ANCA (perinuclear pattern) = anti-MPO antibodies → associated with MPA and EGPA

1. Granulomatosis with Polyangiitis (GPA) - formerly Wegener's

• ANCA: c-ANCA (anti-PR3) - ~90% positive
• Classic triad: Upper airway + Lower airway + Kidneys
  • Upper airway (95%): Chronic sinusitis, nasal septal perforation, saddle nose deformity, epistaxis, otitis media
  • Lower airway: Pulmonary nodules, cavities, hemoptysis (pulmonary capillaritis)
  • Kidney: Crescentic glomerulonephritis (pauci-immune - little/no immune deposits on IF)
• Pathology: Necrotizing granulomatous inflammation + vasculitis (granulomas = key distinguisher from MPA)
• Classic case: Middle-aged person with sinusitis + hemoptysis + hematuria + c-ANCA positive

2. Microscopic Polyangiitis (MPA)

• ANCA: p-ANCA (anti-MPO) - most common
• Key distinguisher from GPA: NO granulomatous inflammation, NO upper airway disease
• Key distinguisher from PAN: Affects glomerular capillaries (renal involvement very common, >80%), affects pulmonary capillaries
• Renal involvement: Most common manifestation - rapidly progressive glomerulonephritis (pauci-immune crescentic GN)
• Can also involve: Skin (palpable purpura), lungs, GI, peripheral nerves
• Classic case: Patient with hemoptysis + hematuria + p-ANCA (pulmonary-renal syndrome)

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

• ANCA: p-ANCA (anti-MPO) - but only ~40-60% positive
• The asthma vasculitis - the only vasculitis that begins with asthma
• Classic triad (three phases):
  1. Allergic phase: Asthma + allergic rhinitis (can precede vasculitis by years)
  2. Eosinophilic phase: Peripheral eosinophilia (>1500 cells/μL or >10%), eosinophilic organ infiltration
  3. Vasculitic phase: Frank small vessel vasculitis
• Key findings: Asthma + palpable purpura + mononeuritis multiplex (wrist/foot drop) + eosinophilia
• Pathology: Necrotizing granulomatous inflammation with abundant eosinophils in granulomas and vasculitis (eosinophils = key distinguisher from GPA)

GROUP B: Non-ANCA Small Vessel Vasculitis (Immune Complex-mediated)

4. IgA Vasculitis (Henoch-Schönlein Purpura - HSP)

• Mechanism: IgA immune complex deposition
• Classic in: Children (after upper respiratory infection); can occur in adults
• Classic tetrad:
  • Palpable purpura (lower limbs - dependent areas; non-thrombocytopenic)
  • Arthritis/arthralgias (knees, ankles)
  • Abdominal pain (GI vasculitis - can cause intussusception)
  • Renal involvement (IgA nephropathy-like: hematuria, proteinuria)
• If: presents with palpable purpura on legs after a sore throat in a child - think HSP

5. Cryoglobulinemic Vasculitis

• Association: Strongly linked to Hepatitis C (unlike PAN which is HBV)
• Cold-precipitable immunoglobulins (cryoglobulins) deposit in vessel walls
• Triad: Purpura + arthralgia + weakness (Meltzer's triad)
• Also: peripheral neuropathy, renal involvement (membranoproliferative GN)

6. Anti-GBM Disease (Goodpasture Syndrome)

• Autoantibodies against the glomerular basement membrane (type IV collagen)
• Pulmonary-renal syndrome: Pulmonary hemorrhage + rapidly progressive GN
• Young men (pulmonary component more prominent), older individuals (renal predominant)

Quick Memory Table

Key Concepts to Cement

1. Large vessel = aorta and its big branches. But the renal artery (even though it goes to a visceral organ) is still "large" - its branches inside the kidney are "medium."
2. PAN vs MPA - both can look similar but: PAN is ANCA-negative, spares the lungs and glomeruli; MPA is ANCA-positive, attacks both
3. GPA vs MPA - both ANCA-associated but: GPA has granulomas and upper airway disease; MPA has neither
4. EGPA is the only vasculitis that starts with asthma - always think of it when a patient with "difficult asthma" develops purpura or neuropathy
5. Kawasaki = IVIG + Aspirin - urgent to prevent coronary aneurysms
6. GCA + blindness risk = start steroids immediately without waiting for biopsy