Management of severe cutaneous drug reactions

For signs and symptoms of a severe cutaneous drug reaction (eg acute generalised exanthematic pustulosis [AGEP], Stevens–Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], drug rash with eosinophilia and systemic symptoms [DRESS]), see here.

Transfer patients with a suspected severe cutaneous drug reaction to the nearest hospital emergency department. If TEN is suspected, transfer the patient to a hospital with a burns unit.

Stop or substitute all suspected drugs when a patient has a severe cutaneous drug reaction, particularly when features suggest SJS or TEN—early cessation of suspected drugs reduces mortality. Also stop or substitute concomitant drugs that interact with, or delay metabolism or elimination of suspected drugs.

Multidisciplinary management (including dermatology and ophthalmology consultation) is essential for patients with severe cutaneous drug reactions. Management of SJS, TEN and DRESS involves replacing fluid and electrolytes, providing adequate pain relief, maintaining body temperature, and monitoring and treating organ dysfunction. Use dressings that do not require frequent changing. Closely monitor for signs of infection.

Controlled trials informing systemic therapy for SJS and TEN (eg corticosteroids, intravenous immunoglobulin) are lacking because these conditions are rare. However, most patients with SJS or TEN will receive systemic corticosteroids, and frequently intravenous immunoglobulin, given the severity of these conditions.

Evidence for systemic corticosteroids reducing mortality from DRESS is limited; however, systemic corticosteroids are used to treat most patients with DRESS. A more prolonged taper of systemic corticosteroids may be needed in patients with DRESS because of the high risk of recurrence on corticosteroid withdrawal. DRESS often follows a protracted course, and long-term observation is recommended because of the risk of symptom reactivation after a period of stabilityMustafa, 2018.

AGEP often responds to topical corticosteroids and cessation of the causative drug. Systemic corticosteroids have not been demonstrated to speed recovery in AGEP.

Patients who have had a severe skin reaction to a drug should wear an alert bracelet or necklace.

If a drug has caused a skin reaction with mucosal involvement, or the reaction has a history of increasing severity, do not rechallenge unless the need (indication) for use is critical and other drugs are not suitable. Any allergy testing or rechallenge must be managed by experts.

Cross-reactivity is common with antiepileptic drugs. In particular, a patient who has had DRESS caused by an antiepileptic must avoid all drugs in the same structural class of antiepileptic. First degree family members of the patient must also avoid the causative antiepileptic drug and all drugs in the same structural class because of the potential for an undiagnosed human leukocyte antigen (HLA) phenotype associated with severe cutaneous drug reactions. Consider pharmacogenetic testing (see Overview of cutaneous drug reactions)—seek specialist advice.