What is the treatment for a suspected drug rash?

Treatment of Drug Rash

Immediately discontinue the suspected causative drug—this is the single most critical intervention that supersedes all other management decisions. 1, 2

Severity Grading and Initial Assessment

Before initiating treatment, grade the rash severity based on body surface area (BSA) involvement and systemic symptoms 3:

• Grade 1 (Mild): <10% BSA involvement, no systemic symptoms
• Grade 2 (Moderate): 10-30% BSA involvement, pruritus or tenderness present
• Grade 3 (Severe): >30% BSA involvement or substantial systemic symptoms
• Grade 4 (Life-threatening): Skin sloughing with >30% BSA involvement

Document the timeline meticulously: Record when each drug was started, the date of rash onset (index date), and calculate the latency period—most drug reactions occur 5-28 days after drug initiation unless there's prior exposure, which shortens the window. 1

Treatment Algorithm by Severity

Grade 1 (Mild Rash)

Apply topical low-potency corticosteroids once or twice daily to affected areas. 3 For facial involvement, use only hydrocortisone 2.5%, desonide 0.05%, or alclometasone 0.05%—never use moderate-to-high potency steroids on the face due to risk of permanent atrophy and telangiectasias. 3

Add non-sedating antihistamines (loratadine 10 mg daily or cetirizine) for daytime pruritus, and sedating antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) at bedtime. 3, 2

Grade 2 (Moderate Rash)

Continue topical corticosteroids and oral antihistamines. 1, 3

If papulopustular features are present (acneiform rash), add oral tetracycline antibiotics for 6 weeks: doxycycline 100 mg twice daily, minocycline 50 mg twice daily, or oxytetracycline 500 mg twice daily. 1

Apply emollients at least once daily, preferably urea-containing (5-10%) moisturizers, and avoid hot showers and excessive soap use. 1, 2

Grade 3 (Severe Rash)

Initiate systemic corticosteroids: prednisone 0.5-1 mg/kg daily for 3-7 days, then taper over 4-6 weeks minimum to prevent rebound. 1, 3 The taper duration is critical—abrupt discontinuation risks recurrence of symptoms. 3

Continue oral antibiotics for 6 weeks if papulopustular features present. 1

If infection is suspected (failure to respond to gram-positive coverage, painful lesions, pustules on arms/legs/trunk, yellow crusts, discharge), obtain bacterial cultures and administer antibiotics for at least 14 days based on sensitivities. 1

Grade 4 (Life-threatening)

Hospitalize immediately with IV methylprednisolone 1-2 mg/kg and urgent dermatology consultation. 3 These patients require intensive care or burn unit management. 4

Critical Red Flags Requiring Immediate Escalation

Obtain urgent dermatology consultation and consider hospitalization if any of the following occur: 3

• Mucosal involvement (eyes, mouth, nose, genitalia)
• Facial edema or angioedema
• Skin sloughing or epidermal detachment (positive Nikolsky sign)
• Systemic symptoms: fever, malaise, lymphadenopathy
• Laboratory abnormalities: eosinophilia, elevated liver enzymes, renal dysfunction
• Symptoms appearing 6+ weeks after drug initiation (suggests DRESS syndrome)

For angioedema with respiratory compromise, administer epinephrine subcutaneously immediately and prepare for resuscitative efforts. 4

Diagnostic Workup for Severe Cases

When Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or DRESS syndrome is suspected 1:

• Full blood count, liver function tests, renal function, electrolytes, coagulation studies
• Chest X-ray
• Skin biopsy from lesional skin adjacent to blister for histopathology
• Second biopsy from periblister skin sent unfixed for direct immunofluorescence to exclude immunobullous disorders
• Bacterial cultures from lesional skin
• Photograph the rash documenting type and extent

Calculate SCORTEN score for SJS/TEN to predict mortality risk. 1

Common Pitfalls to Avoid

Never use prophylactic corticosteroids or antihistamines when initiating medications known to cause rash—this approach has not proven effective and may actually increase rash incidence, particularly with nevirapine and other NNRTIs. 1, 3, 2

Do not rechallenge with the causative drug if SJS, TEN, or DRESS syndrome occurred—rechallenge can lead to serious and possibly fatal reactions occurring much sooner than initial exposure. 3, 2

Avoid moderate-to-ultra-high potency corticosteroids (Class I-V) on facial skin due to increased risk of permanent atrophy and vascular changes. 3

Monitoring and Follow-up

Reassess after 2 weeks either by healthcare professional examination or patient self-report. 1, 3

• If improving: Continue current regimen and taper topical steroids gradually
• If worsening or no improvement: Escalate to next treatment tier

During healing, avoid skin irritants including over-the-counter anti-acne medications, solvents, disinfectants, and excessive sun exposure. 1, 3, 2

Document the reaction thoroughly to prevent future re-exposure to the causative agent and consider cross-reactivity when choosing alternative medications. 2, 5