What is the appropriate management for a suspected drug‑induced rash?

Management of Suspected Drug Reaction Rash

Immediately discontinue the suspected causative drug and initiate treatment based on rash severity graded by body surface area (BSA) involvement, with mild cases (<10% BSA) treated with topical corticosteroids and antihistamines, moderate cases (10-30% BSA) requiring closer monitoring and possible systemic therapy, and severe cases (>30% BSA or with systemic symptoms) necessitating systemic corticosteroids and urgent dermatology consultation. 1, 2

Initial Assessment and Drug Discontinuation

• Stop all suspected causative drugs immediately – this is the single most critical intervention, as continued exposure worsens outcomes and increases mortality risk 1, 3, 4
• Document the complete drug history including start dates, doses, and temporal relationship to rash onset; the typical latency period is 5-28 days after drug initiation (shorter if previous exposure to the same drug) 1
• Assess BSA involvement using the "rule of nines" to grade severity: Grade 1 (<10% BSA), Grade 2 (10-30% BSA), Grade 3 (>30% BSA or Grade 2 with substantial symptoms), Grade 4 (skin sloughing >30% BSA) 1, 2
• Examine for red flags requiring immediate escalation: mucosal involvement, facial/tongue edema, skin sloughing or blistering, fever, lymphadenopathy, or systemic symptoms 1, 2, 5

Treatment Algorithm by Severity Grade

Grade 1 (Mild): <10% BSA

• Apply topical low-potency corticosteroids (hydrocortisone 2.5% or desonide 0.05%) once to twice daily to affected areas 1, 2
• Add oral antihistamines for pruritus: non-sedating agents (loratadine 10 mg daily, cetirizine 10 mg daily, or fexofenadine 180 mg daily) during daytime; sedating agents (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) at bedtime 1, 2
• Apply emollients at least once daily, preferably urea-containing (5%-10%) moisturizers 1, 2
• Continue current medications if not the suspected culprit and monitor for progression 1

Grade 2 (Moderate): 10-30% BSA

• Apply topical moderate-to-potent corticosteroids (triamcinolone 0.1% or betamethasone valerate 0.1%) once to twice daily 1
• Continue oral antihistamines as above 1
• Monitor weekly for improvement; if no improvement after 2 weeks or worsening occurs, escalate to Grade 3 management 1, 2
• Consider dermatology referral and skin biopsy to exclude other diagnoses 1

Grade 3 (Severe): >30% BSA or Grade 2 with Substantial Symptoms

• Withhold or interrupt the causative medication immediately 1
• Initiate systemic corticosteroids: prednisolone 0.5-1 mg/kg orally daily for 3 days, then taper over 1-2 weeks for mild-to-moderate symptoms; for severe symptoms, use IV methylprednisolone 0.5-1 mg/kg, convert to oral when responding, and taper over 2-4 weeks 1, 6
• Continue topical potent corticosteroids and oral antihistamines 1
• Obtain urgent dermatology consultation 1, 2
• Perform punch biopsy and clinical photography for documentation 1
• Obtain laboratory workup: complete blood count with differential (looking for eosinophilia), liver function tests, kidney function tests, and urinalysis 1, 5

Grade 4 (Life-Threatening): Skin Sloughing >30% BSA

• Discontinue all suspected drugs permanently 1
• Administer IV methylprednisolone 1-2 mg/kg immediately 1, 5, 6
• Admit to intensive care unit or burn center with urgent dermatology consultation 1, 5, 3
• Provide supportive care similar to burn management: fluid resuscitation, electrolyte monitoring, infection prevention, wound care, and nutritional support 1, 5, 3
• Consider intravenous immunoglobulin (IVIG) 1-2 g/kg total dose if not responding to systemic corticosteroids 5
• Obtain bacterial cultures from lesional skin and blood cultures if infection suspected 1, 5
• Consult appropriate specialists based on organ involvement (ophthalmology for eye involvement, urology for genitourinary involvement) 5

Specific Considerations for Severe Reactions

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

• These conditions have mortality rates of 5% (SJS) and 30% (TEN) and require immediate recognition 3, 4
• Transfer to burn center or ICU is mandatory for extensive skin detachment 1, 3
• Common causative drugs include sulfonamides, anticonvulsants, allopurinol, and NSAIDs 3, 4
• Perform skin biopsy showing full-thickness epidermal necrosis with subepidermal split 1

DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

• Typically occurs 6+ weeks after drug initiation (longer latency than other drug reactions) 5, 7
• Characterized by facial edema, fever, lymphadenopathy, eosinophilia (>1000/μL), atypical lymphocytes, and hepatitis 5, 4, 7
• Systemic corticosteroids are indicated (unlike in some other severe reactions): IV methylprednisolone with taper over minimum 4 weeks to prevent rebound 5
• Common causative drugs include anticonvulsants (phenytoin, carbamazepine), sulfonamides, allopurinol, and rarely antifungals 5, 4, 7
• May require prolonged immunosuppression due to T-cell-mediated pathophysiology 5

Facial-Specific Management

• Use only low-potency topical corticosteroids on facial skin (hydrocortisone 2.5%, desonide 0.05%, or alclometasone 0.05%) to prevent skin atrophy, telangiectasias, and rosacea-like eruptions 2
• Never apply moderate-to-ultra-high potency corticosteroids (Class I-V) to the face due to high risk of permanent atrophy and vascular changes 2

Critical Pitfalls to Avoid

• Do not use prophylactic corticosteroids or antihistamines when initiating medications known to cause rash, as this has not proven effective and may paradoxically increase rash incidence 2, 5
• Never rechallenge with the causative drug if SJS, TEN, or DRESS syndrome occurred, as this can be fatal 2, 5
• Avoid hot water, excessive soap use, skin irritants (OTC anti-acne medications, solvents), and excessive sun exposure during healing 1, 2
• Do not abruptly stop systemic corticosteroids; taper over minimum 4 weeks (longer for DRESS) to prevent rebound reactions 1, 5

Monitoring and Follow-Up

• Reassess after 2 weeks by healthcare professional examination or patient self-report 1, 2
• If improving: continue current regimen and gradually taper topical corticosteroids over 1-2 weeks 1, 2
• If worsening or no improvement: escalate to next treatment tier and consider alternative diagnoses 1, 2
• For systemic corticosteroid use: taper over minimum 4 weeks (2-4 weeks for Grade 3, longer for DRESS) to prevent rebound 1, 5
• Document the drug allergy clearly in medical records with specific symptoms, timing, and severity to prevent future re-exposure 8

When to Obtain Cultures

• Obtain bacterial cultures from skin lesions if infection is suspected: failure to respond to treatment, painful lesions, pustules on arms/legs/trunk, yellow crusts, or purulent discharge 1, 8
• Administer antibiotics for at least 14 days based on culture sensitivities if infection confirmed 1, 8

Specialist Referral Indications

• Urgent dermatology consultation for: Grade 3 or 4 reactions, diagnostic uncertainty, mucosal involvement, skin sloughing, or failure to improve with primary care management 1, 2
• Consider allergy/immunology referral after acute phase resolves for formal allergy testing to confirm the causative drug and guide future medication use 1, 8