Clinical and prognostic implications of erythema multiforme-like lesions in patients with drug reaction with eosinophilia and systemic symptoms: a prospective case–control study

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe systemic hypersensitivity drug reaction with diverse skin morphologies, including erythema multiforme (EM)-like lesions. Limited literature exists on the prognostic significance of EM-like lesions in patients with DRESS. OBJECTIVES: To compare organ involvement and prognosis of patients with DRESS in those with EM-like lesions and those without EM-like lesions. METHODS: This was a prospective case-control study among patients with DRESS at a tertiary care centre in northern India comparing organ involvement and prognosis of those with EM-like lesions vs. a matched control population without EM-like lesions. Clinical records of 115 patients with DRESS enrolled in the study from January 2018 to August 2024 were reviewed. The diagnosis of DRESS was confirmed using European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria. Based on the RegiSCAR score, 72 patients with probable and definite DRESS were recruited and divided into two groups: those with EM-like lesions (cases, n = 25) and those without (controls, n = 47), matched by age, gender and race. RESULTS: Patients with EM-like lesions had a significantly longer latency between drug intake and symptom onset (P = 0.007), a higher incidence of purpuric lesions (P < 0.001), a less common erythrodermic presentation (P = 0.034), greater palm and sole involvement (P = 0.003), facial oedema (P < 0.001) and mucosal involvement (P = 0.016), compared with controls. Those with EM-like lesions had a significantly elevated total leucocyte count (P = 0.028), higher C-reactive protein levels (P = 0.023), abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) and lower eosinophil counts (P = 0.005), with a greater likelihood of hepatic involvement (odds ratio 6.9). CONCLUSIONS: Patients with DRESS with EM-like lesions experience a more severe disease course with greater hepatic involvement. The presence of these lesions could be used as a clinical marker for more aggressive disease necessitating multidisciplinary care.