What could a rash that looks like the skin is falling off be?

Differential Diagnosis of Skin Sloughing Rash

A rash that looks like skin is falling off most urgently suggests Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), all of which are life-threatening conditions requiring immediate hospitalization and discontinuation of all suspected causative agents. 1

Critical Life-Threatening Conditions to Rule Out First

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

When skin sloughing exceeds 30% of body surface area (BSA) with associated symptoms such as erythema, purpura, or epidermal detachment, this represents Grade 4 skin toxicity requiring immediate emergency hospitalization. 1

Key distinguishing features include:

• Skin or mucous membrane detachment, vesicles, pustules, purpura, or mucous ulcerations 1
• Typically occurs after the 6th week of treatment with certain medications (protease inhibitors, immune checkpoint inhibitors, EGFR inhibitors) 1
• Requires intravenous methylprednisolone 1-2 mg/kg and urgent dermatology consultation 1
• All treatments must be discontinued immediately 1

DRESS Syndrome

DRESS presents with diffuse skin involvement exceeding 50% BSA, often accompanied by eosinophilia and systemic symptoms, and requires immediate discontinuation of triple therapy and emergency hospitalization. 1

• Generally occurs later in treatment course, after the 6th week 1
• Associated with fever and systemic symptoms 1
• Requires immediate hospitalization 1

Algorithmic Approach Based on Clinical Features

Step 1: Assess Extent of Skin Involvement and Associated Features

If >30% BSA with skin detachment, vesicles, or mucosal involvement:

• Suspect SJS/TEN or DRESS 1
• Discontinue ALL medications immediately 1
• Initiate IV methylprednisolone 1-2 mg/kg 1
• Emergency hospitalization with dermatology consultation 1
• Obtain punch biopsy and clinical photography 1

If 10-50% BSA without skin detachment:

• Consider Grade 2-3 drug-induced dermatitis 1
• Withhold causative agent 1
• Initiate topical potent steroids 1
• Consider oral prednisolone 0.5-1 mg/kg for 3 days if Grade 3 1

Step 2: Evaluate for Infectious Causes

Rocky Mountain Spotted Fever (RMSF) with severe progression:

• Maculopapular rash that becomes petechial, involving palms and soles, appearing by day 5-6 indicates advanced disease 1
• Associated with fever, headache, and tick exposure 3-12 days prior 1
• Case-fatality rate of 5-10% if untreated 1
• Requires immediate doxycycline regardless of age 1

Step 3: Consider Medication History

Common causative agents for severe skin sloughing reactions:

• Protease inhibitors (telaprevir, boceprevir) - 54% develop skin problems, with 3 cases of SJS reported per 3000 patients 1
• Immune checkpoint inhibitors - rare but documented cases of Grade 4 toxicity 1
• EGFR inhibitors - can progress to severe desquamation 1
• Antibiotics (vancomycin, ceftazidime, sulfonamides) 2

Management Priorities by Severity

Grade 4 (Skin Necrosis/Sloughing >30% BSA)

Immediate actions:

• Discontinue ALL suspected medications 1
• IV methylprednisolone 1-2 mg/kg 1
• Emergency admission to burn unit or intensive care 1
• Urgent dermatology and wound specialist consultation 1
• Obtain bacterial/viral/fungal cultures if infection suspected 1
• Check blood granulocyte count and blood cultures if fever present 1

Grade 3 (Moist Desquamation, Bleeding with Minor Trauma)

Management approach:

• Withhold causative agent until Grade 1 or less 1
• Systemic corticosteroids: prednisolone 0.5-1 mg/kg for 7 days with weaning over 4-6 weeks 1
• High-potency topical steroids 1
• Weekly skin assessments 1
• Dermatology consultation mandatory 1

Critical Pitfalls to Avoid

Never rechallenge patients who have had urticarial, bullous, or erythema multiforme-like eruptions with the suspected causative drug, as this can be very dangerous. 2

Do not use systemic steroids in neutropenic patients with fever without careful consideration, as steroids can mask infection symptoms. 2

Do not delay treatment waiting for the classic triad of symptoms - early recognition and intervention are critical for survival in SJS/TEN and RMSF. 1

Avoid topical antibiotics prophylactically; reserve them only for documented superinfection. 1

When to Obtain Specialist Consultation

Immediate dermatology consultation is required when:

• Grade 2 or higher skin lesions develop with suspected drug reaction 1
• Any suspicion of SJS, TEN, or DRESS 1
• Skin sloughing exceeds 30% BSA 1
• Presence of mucosal involvement or systemic symptoms 1