DRESS Syndrome due to benzylpenicillin with cross-reactivity to amoxicillin

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome carries a 10% mortality and is one of the severe cutaneous adverse reactions, which also includes acute generalized exanthematous pustulosis and Stevens-Johnson syndrome/toxic epidermal necrolysis.1 DRESS syndrome can present with an extensive maculopapular exanthema, fever, lymphadenopathy, internal organ involvement (ie, renal and hepatic), eosinophilia, and other hematological abnormalities (ie, lymphopenia and atypical lymphocytes).2 The diagnosis is typically reached using the RegiSCAR (European Registry of Severe Cutaneous Adverse Reaction) validation scoring criteria and can be graded accordingly (ie, possible, probable, or definite case).3 Treatment involves withdrawal of the likely culprit drug and corticosteroids (ie, topical or oral).2 Here, we present a novel case of DRESS syndrome due to benzylpenicillin with cross-reactivity to amoxicillin confirmed by delayed intradermal and patch tests. DRESS syndrome is a severe potentially life-threatening delayed-type drug reaction with an estimated incidence ranging from 1 in 1000 to 1 in 10,000 drug exposures.2 Various pathogenic mechanisms have been proposed for DRESS syndrome including viral reactivation (ie, human herpesvirus 6 & 7, EBV, cytomegalovirus), cell-mediated hypersensitivity (ie, CD4+/CD8+ T-cell–mediated), and genetic associations (ie, HLA-B*58:01 with allopurinol).4,5 A delayed onset of 2 to 6 weeks after initiation of the causative drug is typical of its clinical course.2 Although the RegiSCAR validation scoring criteria is frequently used for evaluating suspected DRESS syndrome (or drug-induced hypersensitivity syndrome), there are heterogeneous diagnostic criteria also available such as the Japanese consensus group diagnostic criteria, which also include human herpesvirus 6 reactivation.6 DRESS syndrome has been previously associated with anticonvulsants, antimicrobials, and anti-inflammatory agents.1 In a large retrospective literature review of DRESS syndrome,2 carbamazepine was the most frequently reported causative agent. Patch testing has reportedly higher specificity than intradermal testing and conversely intradermal testing has higher sensitivity than patch testing. Because of concerns regarding systemic reactivation, it is generally recommended in severe cutaneous adverse reactions to perform patch testing first, followed by intradermal testing if the patch test results are negative.8 In conclusion, we de