DermatologyTier 2Disease (DEADMAN)

Cutaneous manifestations of adverse effects of therapeutic interventions - drug hypersensitivity syndrome

Description

Drug hypersensitivity syndrome (DRESS - Drug Reaction with Eosinophilia and Systemic Symptoms) - a severe, delayed-onset drug reaction causing widespread rash, fever, eosinophilia, and internal organ involvement - a T cell-mediated hypersensitivity reaction distinct from immediate IgE-mediated drug allergy

Rare but carries significant mortality if unrecognised (from fulminant organ failure, particularly hepatic); classic culprit drugs include anticonvulsants (carbamazepine, phenytoin, lamotrigine), allopurinol, and sulfonamide antibiotics

A delayed T cell-mediated hypersensitivity reaction, with onset typically 2-8 weeks after starting the causative drug (much later than immediate IgE-mediated reactions, and later than most other cutaneous drug eruptions) - human herpesvirus 6 (HHV-6) reactivation is thought to contribute to the pathogenesis and prolonged/relapsing course seen in some cases

Widespread morbilliform rash + fever + facial oedema + lymphadenopathy, with eosinophilia and evidence of internal organ involvement (most commonly hepatitis - the leading cause of DRESS-related mortality; also nephritis, myocarditis, pneumonitis)
The delayed onset (weeks after drug start) is a key diagnostic clue distinguishing DRESS from more immediate drug eruptions - a patient may have already been established on the causative drug for some time before symptoms begin, making the temporal link less obvious than with immediate reactions

Immediate cessation of the causative drug is essential; systemic corticosteroids for significant organ involvement
Monitor closely for relapse/flare even after apparent improvement, given the HHV-6 reactivation-associated prolonged/biphasic course some patients experience
Screen for and manage the specific organ involvement identified (particularly liver function, given hepatitis is the dominant mortality driver)

HLA-B15:02 and HLA-B58:01 (pharmacogenetic risk markers for carbamazepine- and allopurinol-associated severe cutaneous reactions respectively, relevant to pre-treatment screening in specific populations), Stevens-Johnson syndrome/toxic epidermal necrolysis (a different, though sometimes overlapping, severe drug reaction spectrum), HHV-6 reactivation

DRESS's delayed onset (weeks, not days) after starting the causative drug is a frequently missed diagnostic clue - the causative drug is often not the most recently started medication, and a careful medication timeline over the preceding weeks-months is essential to correctly identify the culprit

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