P-ANCA (Perinuclear ANCA): Significance in Dermatology

What is P-ANCA?

ANCA-Associated Vasculitides (AAV) with Dermatological Relevance

ANCA frequencies across AAVs — p-ANCA/MPO-ANCA dominates in MPA and drug-induced vasculitis (Dermatology, 5th ed.)

1. Microscopic Polyangiitis (MPA) — p-ANCA is the dominant pattern

• ANCA positivity: ~70% positive; p-ANCA (anti-MPO) more frequent than c-ANCA
• Skin involved in 44% — the skin may be the initial presenting feature
• Cutaneous findings:
  • Purpuric papules and macules (most common)
  • Livedo reticularis (in ~2/3 of those with skin-first presentation)
  • Retiform purpura, cutaneous ulcers, digital ischemia
  • Necrotizing leukocytoclastic vasculitis (LCV) in reticular dermis on biopsy
• Systemic: glomerulonephritis (80–90%), pulmonary capillaritis, vasculitic neuropathy (58%)
• Distinguishing feature from PAN: presence of GN, pulmonary symptoms; ANCA rarely positive in PAN

2. Granulomatosis with Polyangiitis (GPA) — c-ANCA dominant, but ~10% have p-ANCA

• ANCA positivity: ~90% in active generalized disease
  • ~90% are c-ANCA (anti-PR3); the remainder are p-ANCA (anti-MPO)
• Skin involved in ~1/3 of patients at presentation; cutaneous involvement is a risk marker for severe systemic disease (GN, alveolar hemorrhage)
• Cutaneous findings:
  • Purpuric papules/macules, petechiae
  • Papulonecrotic lesions (especially extensor surfaces, elbows)
  • Subcutaneous nodules, ulcerations resembling pyoderma gangrenosum
  • "Strawberry gums" — hypertrophic gingivitis, characteristic and biopsy-accessible
  • Saddle-nose deformity, nasal septal perforation (mucosal involvement)
  • Livedo reticularis is rare in GPA
• Histology: LCV ± granulomatous inflammation; palisaded granulomas with multinucleated giant cells

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

• ANCA positivity: ~40–50%; predominantly p-ANCA (anti-MPO)
• Associated with asthma, peripheral eosinophilia (>1000 cells/μL) — helps differentiate from asthma/atopy
• Skin: purpura, papulonecrotic nodules ("Churg-Strauss nodules"), subcutaneous nodules

P-ANCA in Drug-Induced Vasculitis — Critical Dermatological Context

• Drugs causing p-ANCA/MPO-ANCA-positive vasculitis:
  • Propylthiouracil (PTU)
  • Minocycline
  • Hydralazine
  • Allopurinol, sulfonamides, gold, thiazides, phenytoin
• Key clue: Both c-ANCA AND p-ANCA positive simultaneously → suspect drug-induced vasculitis, including levamisole-tainted cocaine
• Levamisole-adulterated cocaine (present in up to 70% of U.S. seized cocaine):
  • Produces ecchymotic purpura/necrosis with predilection for ears, nose, thighs, buttocks
  • Both c-ANCA and p-ANCA can be elevated
  • c-ANCA reacts with human neutrophil elastase (HNE-ANCA) — patients with true GPA/MPA are HNE-ANCA negative — useful distinguishing test
  • Also causes agranulocytosis (atypical for true AAV)

P-ANCA in Non-Vasculitic Dermatological Conditions

Diagnostic Algorithm for Dermatologists

Skin vasculitis suspected
       ↓
Screen: IIF for ANCA pattern
       ↓
Positive p-ANCA pattern
       ↓
Confirm with ELISA: Anti-MPO antibody?
   ├─ YES → Strongly suggests MPA, EGPA, or drug-induced AAV
   │         Assess: renal function, pulmonary symptoms, drug history
   └─ NO  → Atypical ANCA — consider IBD, SLE, infection
              (low specificity for primary vasculitis)

Key Takeaways

1. p-ANCA alone (by IIF) has low specificity — MPO confirmation by ELISA is essential
2. p-ANCA/MPO-ANCA is the hallmark of MPA, and skin is involved in nearly half of MPA cases — often as the presenting feature
3. ~10% of GPA patients have p-ANCA (not c-ANCA); these must be distinguished from MPA
4. Dual positivity (p-ANCA + c-ANCA) should always raise suspicion for drug-induced vasculitis or levamisole-cocaine exposure
5. HNE-ANCA is a useful differentiator: positive in cocaine/levamisole vasculitis, negative in true GPA/MPA
6. ANCA testing does not replace clinical evaluation, histopathology, and organ-specific investigations
7. ANCA positivity in skin-limited vasculitis warrants systemic workup (renal, pulmonary), since AAV underlies ~10% of such cases