What is the management approach for patients presenting with drug eruptions?

Management of Drug Eruptions

Immediately discontinue all suspected medications upon recognition of a drug eruption, as this is the single most critical intervention that directly impacts prognosis and mortality. 1

Initial Assessment and Drug Identification

The first priority is identifying and stopping the causative agent:

• Obtain a comprehensive medication history covering the previous 2 months, including prescription drugs, over-the-counter medications, herbal supplements, and complementary therapies 2, 1
• Document exact dates when medications were started, stopped, or dose-escalated, along with the index date when first symptoms appeared 2, 1
• Earlier withdrawal of drugs with short elimination half-lives is associated with better survival, particularly in severe reactions like Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) 3
• Document the reaction thoroughly in the medical record to prevent future re-exposure, including the specific drug implicated, description of the reaction, and sites of involvement 2

Severity-Based Treatment Algorithm

Mild to Moderate Eruptions (Localized Involvement)

For patients with limited body surface area involvement without systemic symptoms:

• Apply topical moderate-to-high potency corticosteroids such as mometasone furoate 0.1% or betamethasone valerate 0.1% ointment twice daily to affected areas 2, 1
• Prescribe oral antihistamines for pruritus: second-generation agents like loratadine 10 mg daily for daytime use, or first-generation agents like diphenhydramine 25-50 mg or hydroxyzine 25-50 mg for nighttime sedation 1
• Apply emollients regularly and advise patients to avoid hot showers, excessive soap use, and sun exposure 2

Moderate to Severe Eruptions (Widespread Involvement)

For patients with extensive body surface area involvement but without life-threatening features:

• Continue topical high-potency corticosteroids to all affected areas 1
• Add GABA agonists as second-line therapy for persistent pruritus unresponsive to antihistamines: pregabalin 25-150 mg daily or gabapentin 900-3600 mg daily 1
• Consider systemic corticosteroids (prednisone 0.5-1 mg/kg body weight) for severe cases, though use cautiously as they may be deleterious in advanced TEN 1

Life-Threatening Eruptions (SJS/TEN/DRESS)

Hospitalization is mandatory for extensive body surface area involvement, systemic symptoms, or suspicion of progression to SJS/TEN. 2

For patients with severe cutaneous adverse reactions:

• Admit to burn unit or intensive care unit immediately and place under supervision of a dermatologist 4
• Administer IV methylprednisolone (or equivalent) 0.5-2 mg/kg and convert to oral corticosteroids on response, weaning over at least 4 weeks 4
• Provide supportive care as for major burns: warming of the environment, correction of electrolyte disturbances, high caloric intake, fluid and electrolyte balance, minimizing insensible water losses, and prevention of sepsis 4, 3
• Treat skin with topical emollients and petrolatum-based products, oral antihistamines, and high-strength topical corticosteroids 4
• Perform daily reviews of oral, ocular, and urogenital mucosa during acute illness 4

Important caveat: The usual prohibition of corticosteroids for SJS/TEN does not apply to immune checkpoint inhibitor-induced reactions, where the underlying mechanism is T-cell immune-directed toxicity requiring adequate immunosuppression 4. However, systemic corticosteroids have been shown to be deleterious in cases of advanced TEN from traditional drug reactions 3.

Specific Eruption Types

Fixed Drug Eruption

• Permanently discontinue the causative drug as the cornerstone of management 2
• Apply topical moderate-to-high potency corticosteroids twice daily to affected areas 2
• Educate patients that the reaction will recur at the same anatomical sites if re-exposed to the drug or structurally similar compounds 2
• Follow-up at 4 weeks to confirm resolution and reinforce avoidance 2

Papulopustular Rashes (from targeted cancer therapies)

• Initiate oral antibiotics for 6 weeks: doxycycline 100 mg twice daily, minocycline 50 mg twice daily, or oxytetracycline 500 mg twice daily, combined with topical low-to-moderate potency steroids 1
• Obtain bacterial/viral/fungal cultures if superinfection is suspected, as bacterial superinfection requires culture-directed antibiotic therapy 1

Palmar-Plantar Eruptions (from chemotherapy)

• Apply cooling measures (cold gloves or socks) during infusions for drugs like paclitaxel, docetaxel, and liposomal doxorubicin 1

Drug-Induced Pemphigus

• Stop the offending drug immediately (particularly thiol drugs, phenol drugs, or other implicated agents) 1
• Recognize that 50% of cases will resolve with drug withdrawal alone (drug-triggered pemphigus), while the other 50% will require treatment as idiopathic pemphigus 1
• Consider transitioning to steroid-sparing options (e.g., IVIG and rituximab) if bullous pemphigoid is diagnosed, to avoid long-term systemic steroid use 4

Mucosal and Organ-Specific Management

Oral Involvement

• Apply benzydamine hydrochloride oral spray every 3 hours, particularly before eating 4
• Use antiseptic oral rinse containing chlorhexidine twice daily 4
• Use potent topical corticosteroid mouthwash (e.g., betamethasone sodium phosphate) four times daily 4

Urogenital Involvement

• Perform daily urogenital review during acute illness 4
• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours through the acute illness 4
• Use potent topical corticosteroid ointment once daily to involved, but non-eroded, surfaces 4
• Apply silicone dressing (e.g., Mepitel) to eroded areas 4

Airway Involvement

• Respiratory symptoms and hypoxemia on admission should prompt early discussion with an intensivist and rapid transfer to an ICU or burn center, where fiberoptic bronchoscopy should be undertaken 4

Discharge Planning and Prevention

• Provide written information about drug(s) to avoid, including structurally similar compounds that may cross-react 4, 2
• Encourage the patient to wear a MedicAlert bracelet 4
• Document drug allergy in the patient's notes and inform all doctors involved in the patient's care 4
• Report the episode to national pharmacovigilance authorities 4
• Organize dermatology outpatient appointment within a few weeks of discharge, and ophthalmology appointment if required 4

Diagnostic Testing

Routine drug hypersensitivity testing is NOT recommended following an episode of SJS/TEN. 4

However, seek specialist advice on formal drug hypersensitivity testing in three specific scenarios: (i) the culprit drug is not known, (ii) medication avoidance is detrimental to the individual, or (iii) accidental exposure is possible 4

Critical Pitfalls to Avoid

• Never rechallenge with a drug that caused a severe life-threatening reaction 4
• Do not delay drug withdrawal while awaiting diagnostic confirmation—clinical suspicion alone warrants immediate discontinuation 1, 3
• Avoid systemic corticosteroids in advanced TEN from traditional drug reactions, as they have been shown to increase mortality 3
• Do not overlook the possibility of multiple causative agents—patients on multiple medications require careful evaluation of all potential culprits 1
• Recognize that drug reactions can occur days after completion of infusion, not just during administration 4