Differential Diagnosis of Necrosis

Introduction

Cutaneous necrosis refers to the death of skin tissue, presenting as darkened, devitalized areas that may progress to eschar formation. Recognizing necrosis is critical as it often indicates vascular occlusion, severe infection, or drug reaction requiring urgent intervention. The pattern, distribution, and clinical context guide diagnosis.

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42.1 Causes of Cutaneous Necrosis

42.1.1 Vascular Occlusion

Calciphylaxis (Calcific Uremic Arteriolopathy)

• Setting: End-stage renal disease (ESRD), Dialysis patients. Also non-uremic (obesity, warfarin, hyperparathyroidism).
• Pathogenesis: Calcium deposition in media of small arteries → Thrombosis → Ischemia → Necrosis.
• Clinical Features:
  • Livedo racemosa.
  • Painful, indurated plaques → Necrotic ulcers with eschar.
  • Distribution: Trunk, Thighs, Buttocks, Abdomen (proximal > distal).
• Prognosis: Very poor (50-80% 1-year mortality).
• Management: Wound care, Pain management, Sodium thiosulfate, Correct calcium/phosphate, Consider parathyroidectomy.

Warfarin-Induced Skin Necrosis

• Pathogenesis: Warfarin inhibits Vitamin K-dependent clotting factors. Protein C (shortest half-life) is depleted first → Transient hypercoagulable state → Microvascular thrombosis.
• Timing: Typically days 3-6 of warfarin initiation.
• Risk Factors: Protein C or S deficiency, High warfarin loading dose without bridging anticoagulation.
• Clinical Features:
  • Painful purpura → Well-demarcated necrosis.
  • Distribution: Fatty areas (breasts, buttocks, thighs, abdomen).
• Prevention: Bridge with heparin when initiating warfarin, especially in high-risk patients.

Heparin-Induced Skin Necrosis

• Pathogenesis: HIT (Type II) antibodies cause platelet activation and thrombosis.
• Features: Necrosis at heparin injection sites OR distant sites.
• Associated with HIT → Thrombocytopenia + Thrombosis.

Cholesterol Emboli Syndrome

• Setting: Post-vascular procedure, Anticoagulation.
• Features: Livedo + "Blue toe" + Necrosis of digits/toes despite palpable pulses.

Antiphospholipid Syndrome (APS)

• Features: Thrombosis → Digital necrosis/gangrene.
• Catastrophic APS (CAPS): Multi-organ thrombosis with high mortality.

42.1.2 Infectious Causes

Necrotizing Fasciitis

[!CAUTION] SURGICAL EMERGENCY

• Definition: Rapidly progressive, life-threatening infection of fascia and subcutaneous tissue.
• Types:
  • Type I: Polymicrobial (anaerobes + aerobes). Often post-surgical, diabetic.
  • Type II: Monomicrobial (GAS = S. pyogenes; or S. aureus). Can occur in healthy individuals.
• Clinical Features:
  • Pain out of proportion to clinical findings (key early clue).
  • Erythema, Swelling, Bullae, Crepitus (gas-forming organisms).
  • Rapid progression.
  • Systemic toxicity: Fever, Tachycardia, Hypotension.
  • Necrosis with "dishwater gray" discharge.
• Diagnosis: Clinical suspicion. CT may show gas. DO NOT delay for imaging.
• Management: IMMEDIATE surgical debridement + IV broad-spectrum antibiotics + ICU.

Gas Gangrene (Clostridial Myonecrosis)

• Causative Agent: Clostridium perfringens.
• Setting: Trauma, Contaminated wounds, Surgical.
• Features: Severe pain, Crepitus, Bronze discoloration → Necrosis, "Sweet" odor.
• Management: Emergent surgical debridement, High-dose Penicillin, Hyperbaric oxygen.

Ecthyma Gangrenosum

• Causative Agent: Pseudomonas aeruginosa (usually in neutropenic patients).
• Features: Erythematous macule → Hemorrhagic vesicle/bulla → Necrotic ulcer with black eschar and surrounding erythema.
• Reflects bacteremia.

Meningococcemia (Purpura Fulminans)

• Rapidly evolving petechiae → Purpura → Necrosis.
• Symmetric, Acral distribution.
• Waterhouse-Friderichsen syndrome (adrenal necrosis).

42.1.3 Drug-Induced Necrosis

Vasopressors (Pressors) Extravasation

• High-dose vasopressors (Norepinephrine, Dopamine) → Peripheral vasoconstriction → Digital necrosis.
• Also extravasation at IV site → Local necrosis.

Levamisole-Adulterated Cocaine

• Mechanism: Levamisole (antihelminthic used to cut cocaine) causes vasculitis/thrombosis.
• Clinical Features: Retiform purpura → Necrosis. Characteristically involves ears and nose.
• Lab: May have ANCA positivity.

42.1.4 Other Causes

Pyoderma Gangrenosum (Covered in Ch. 41)

• Neutrophilic dermatosis. Necrotic ulcers with undermined violaceous borders.

Cryoglobulinemia / Cryofibrinogenemia

• Cold-precipitating proteins → Vascular occlusion → Necrosis.

Spider Bites (Loxoscelism)

• Brown Recluse Spider (Loxosceles reclusa): Necrotic arachnidism.
• Features: Pain at bite site → Expanding erythema → Central necrosis ("red, white, and blue" sign).
• Geographic: Southern/Central US.

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42.2 Diagnostic Approach

History

• Timeline: Acute vs. Chronic.
• Pain: Severe pain out of proportion → Necrotizing fasciitis.
• Risk Factors: ESRD (Calciphylaxis), Warfarin, Heparin, DM, Immunosuppression, Cocaine use.

Examination

• Distribution: Symmetric acral (Meningococcemia, Pressors), Proximal fatty (Calciphylaxis, Warfarin), Ears/Nose (Levamisole-Cocaine).
• Crepitus: Gas gangrene, Necrotizing fasciitis (Type I).
• Systemic Signs: Fever, Hypotension, Tachycardia → Sepsis/Necrotizing infection.

Investigations

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42.3 Diagnostic Algorithm

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42.4 Summary Comparison Table

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42.5 Clinical Pearls

1. Pain out of proportion + Crepitus + Systemic toxicity → Necrotizing fasciitis. Surgical emergency. Do NOT delay for imaging.
2. ESRD + Livedo + Necrotic ulcers (proximal) → Calciphylaxis. Poor prognosis. Sodium thiosulfate.
3. Warfarin Day 3-6 + Fatty area necrosis → Warfarin-induced necrosis. Stop warfarin, give Vitamin K, Heparin, consider Protein C concentrate.
4. Cocaine + Ear/Nose necrosis + ANCA positivity → Levamisole-adulterated cocaine.
5. Neutropenic patient + Necrotic ulcer → Ecthyma gangrenosum. Cover Pseudomonas.
6. Symmetric acral necrosis in sick patient → Meningococcemia / Purpura fulminans / DIC.