A 21-year-old woman, diagnosed with epilepsy and well-controlled type 1 diabetes mellitus, was admitted to the Department of Rheumatology and Immunology, University Hospital in Kraków due to a severe, pruritic, maculopapular rash covering more than 50% of her skin for the past 2 days (Figure 1A–1C) and a week-long fever up to 39 °C. Further examination revealed enlarged submandibular and cervical lymph nodes. Her medical history showed that lamotrigine was initiated 2 weeks ago following 2 recent tonic-clonic seizures, in addition to previously used valproate (VPA). Laboratory tests showed white blood cell (WBC) count of 8380/µl (reference range [RR], 4000–10 000/µl), eosinophils 440/µl (RR, 40–450/µl), alanine aminotransferase (ALT) level of 37 U/l (RR, 10–35 U/l), aspartate aminotransferase (AST) 35 U/l (RR, 10–35 U/l), ammonia 32 µmol/l (RR, 11–51 µmol/l), N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of 245 pg/ml (RR <⁠125 pg/ml) and C-reactive protein (CRP) level of 2.81 mg/l (RR <⁠5 mg/l). Electrocardiogram showed no abnormalities. Infections with hepatitis B and C viruses, cytomegalovirus, Epstein–Barr virus, and HIV were ruled out. Initially, methylprednisolone (1 mg/kg/day) and rupatadine (10 mg twice daily) were administered, resulting in a gradual improvement of the skin lesions. However, from the third day of hospitalization, laboratory tests showed signs of acute hepatic injury (ALT, 1046 U/l; AST, 907 U/l; ammonia, 103 µmol/l), leukocytosis (WBC, 14 850/µl) with elevated percentage of atypical lymphocytes in peripheral smear, and an increase in NT-proBNP level to 870 pg/ml. Unfortunately, the exact eosinophil level has not been evaluated due to the presence of atypical lymphocytes, which interfered with the results. Despite a lack of skin biopsy, a diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) was established based on the clinical presentation and the laboratory results, including the Registry of Severe Cutaneous Adverse Reactions scoring system. Rupatadine was continued, while methylprednisolone dose was increased to 250 mg intravenously for 4 consecutive days, and cyclosporine was initiated at a dose of 4 mg/kg/day. Additionally, hepatoprotective drugs (ornithine, rifaximin, lactulose) were administered. Upon normalization of liver parameters and regression of skin lesions, the patient was discharged home. Unfortunately, 6 days later, she was readmitted to the hospital due to recurrence of fine-spotted rash covering more than 50% of the skin and deterioration of her general condition despite no reduction in the daily dose of methylprednisolone. Blood tests showed ALT at 97 U/l, WBC at 12 510/µl, eosinophils at 400/µl, and CRP below 1 mg/l. After a neurologic consultation, a skin reaction to levetiracetam was diagnosed, and epilepsy treatment was continued with VPA alone. The use of rupatadine, methylprednisolone at a dose of 32 mg with subsequent gradual tapering to discontinuation within 1 month from discharge, and cyclosporine were also sustained. On follow-up, laboratory investigations normalized and skin changes resolved 1.5 months after discharge from the hospital.

Figure 1. Pruritic maculopapular rash on the left forearm (A), left thigh (B), and the back (C)

DRESS syndrome is a severe adverse drug reaction characterized by a rash, accompanied by high fever, eosinophilia, and organ involvement, primarily affecting the liver, heart, lungs, and kidneys.1,2 Multiple organ failure, hepatic necrosis, shock, pulmonary hemorrhage, and sepsis are the primary predictors of mortality, with a rate that can reach up to 20%.2,3 A latency phase typically spans 2 to 8 weeks.4 Roughly 75% of cases are attributed to high-risk drugs, including antiepileptic agents such as lamotrigine.5 Treatment includes discontinuation of the medication that causes DRESS syndrome, and initiation of systemic glucocorticoids, cyclosporine, intravenous immunoglobulins, and plasmapheresis.2,5