What is the workup and management for a patient with suspected drug-induced exfoliative dermatitis?

Workup for Drug-Induced Exfoliative Dermatitis

Immediately discontinue all suspected medications and perform a complete body surface area assessment with particular attention to all mucous membranes (oral, ocular, genital) to differentiate between exfoliative dermatitis and life-threatening severe cutaneous adverse reactions (SCARs) like Stevens-Johnson syndrome or toxic epidermal necrolysis. 1, 2

Initial Clinical Assessment

Physical Examination Priorities

• Examine ALL mucous membranes systematically (oral cavity, conjunctivae, urogenital areas) as mucosal involvement suggests progression to SJS/TEN rather than simple exfoliative dermatitis 1
• Calculate body surface area (BSA) involvement with skin sloughing, erythema, or blistering—if >10% BSA with mucosal involvement, this is grade 3-4 SCAR requiring immediate burn unit admission 1
• Document findings with serial clinical photography to track progression or improvement 1
• Assess for systemic signs including fever, tachycardia, hypotension, or respiratory symptoms that warrant ICU-level care 1

Medication History

• Obtain complete drug history for the preceding 2 months, including prescription medications, over-the-counter drugs, herbal supplements, and any recent medication changes 3, 4
• Identify high-risk medications such as lamotrigine, allopurinol, anticonvulsants, sulfonamides, and NSAIDs that commonly cause exfoliative reactions 2, 5

Laboratory Workup

Essential Blood Tests

• Complete blood count with differential to assess for eosinophilia (suggests DRESS syndrome) and infection 1, 3
• Comprehensive metabolic panel including liver function tests (elevated in DRESS/DIHS) and renal function 1, 3
• Inflammatory markers (ESR, CRP) 3
• Blood cultures if febrile to rule out sepsis 1

Additional Testing for DRESS Syndrome

• Urinalysis to assess for associated nephritis if DRESS is suspected 1
• Viral serology (EBV, CMV, HHV-6) if systemic symptoms suggest DRESS 2

Skin Biopsy

Perform skin biopsies from two sites: lesional skin for histopathology (to assess for full-thickness epidermal necrosis characteristic of SJS/TEN) and perilesional skin for direct immunofluorescence (to exclude autoimmune blistering disorders like pemphigus or pemphigoid) 1, 3

Critical Differential Diagnosis Considerations

Rule Out Severe Cutaneous Adverse Reactions (SCARs)

The most important distinction is between simple exfoliative dermatitis and life-threatening SCARs 2:

• Stevens-Johnson syndrome/Toxic epidermal necrolysis: Mucosal involvement, skin sloughing >10% BSA, positive Nikolsky sign, full-thickness epidermal necrosis on biopsy 1
• DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms): Fever, facial edema, eosinophilia, lymphadenopathy, liver dysfunction, typically 2-6 weeks after drug exposure 1, 2
• Acute generalized exanthematous pustulosis (AGEP): Numerous sterile pustules, rapid onset within 1-2 days 1

Exclude Other Causes

• Cutaneous T-cell lymphoma (may not manifest for months to years after initial presentation—requires long-term follow-up) 4
• Autoimmune blistering disorders (pemphigus vulgaris, bullous pemphigoid) via direct immunofluorescence 1, 3
• Infectious causes including scabies, especially in immunocompromised patients 1

Immediate Management Decisions

Hospitalization Criteria

Admit immediately to burn unit or ICU if: 1

• Mucosal involvement with blistering or erosions
• Skin sloughing ≥10% BSA
• Respiratory symptoms or hypoxaemia
• Systemic instability (fever, hypotension, tachycardia)
• Suspected SJS/TEN or DRESS

Outpatient Management (Mild Cases Only)

Only manage outpatient if: 6

• <10% BSA involvement
• No mucosal involvement
• No systemic symptoms
• Confirmed simple exfoliative dermatitis without SCAR features

Supportive Care Priorities

Fluid and Electrolyte Management

• Monitor for fluid losses from damaged skin barrier and replace appropriately 1, 4
• Prevent insensible water losses with appropriate wound care 1

Temperature Regulation

• Maintain thermoregulation as extensive skin involvement impairs temperature control 4

Infection Prevention

• Monitor closely for secondary bacterial infection as skin barrier disruption increases infection risk 1, 4
• Consider prophylactic antibiotics only in severe cases with extensive skin loss 4

Documentation and Follow-Up

Allergy Documentation

• Document drug allergy in medical records and inform all treating physicians 1
• Provide written information about drugs to avoid 1
• Encourage MedicAlert bracelet for severe reactions 1
• Report to national pharmacovigilance authorities 1

Specialist Referrals

• Dermatology follow-up within 2-4 weeks of discharge or initial presentation 1, 3
• Ophthalmology evaluation if any ocular involvement 1
• Consider patch testing if culprit drug cannot be identified with confidence or if medication avoidance is detrimental 1

Common Pitfalls to Avoid

Do not perform routine drug hypersensitivity testing after an episode—it is not recommended and has poor sensitivity/specificity 1

Do not confuse drug-induced exfoliative dermatitis with SJS/TEN, as the latter requires aggressive immunosuppression and burn unit care with significantly worse prognosis 3

Do not delay corticosteroid therapy in immune-mediated drug reactions (unlike traditional teaching for SJS/TEN, immune checkpoint inhibitor-induced SCARs and DRESS require early immunosuppression) 1

Do not miss cutaneous T-cell lymphoma as the underlying cause—this may not become apparent for months to years and requires long-term dermatology surveillance 4