CPC13: Two cases of trimethoprim-induced drug reaction with eosinophilia and systemic symptoms

A. Connolly,¹ S. Wash,¹ M. Philippidou,² J. Salisbury ² and D. Creamer¹

¹Dermatology Department and ²Histopathology Department, King’s College Hospital, London, UK

A 22-year-old female medical student was commenced on trimethoprim 300 mg q12h for acne. Six weeks after starting trimethoprim she developed an illness characterized by fever, nausea, malaise, myalgia and a rash. She was seen in her local emergency department and a viral illness was diagnosed. She re-presented 1 week later in acute liver failure and was transferred to the liver intensive treatment unit (LITU). Examination revealed jaundice, a macular exanthem with facial oedema and extensive lymphadenopathy [bloods: alanine transaminase (ALT) 4143 IU L^–1; bilirubin 417 μmol L^–1; international normalized ratio (INR) 6·2; eosinophils 0·95 × 10⁹ cells L^–1; lymphocytes 5·91 × 10⁹ cells L^–1). Viral hepatitis was excluded. Skin biopsy revealed spongiosis, focal basal vacuolar degeneration and scattered apoptotic keratinocytes. A diagnosis of trimethoprim-induced drug reaction with eosinophilia and systemic symptoms (DRESS) was made. The day after admission she developed grade 4 hepatic encephalopathy and required mechanical ventilation, haemodialysis and vasopressor support. She received intravenous (IV) methylprednisolone 250 mg on three consecutive days. On the fifth day of her LITU admission she underwent an orthotopic liver transplant. She recovered quickly; her liver transplant is functioning well on tacrolimus 6 mg q24h. An 18-year-old man was commenced on trimethoprim 300 mg q12h for acne. After 5 weeks of treatment he developed an illness characterized by fever, anorexia and a rash. He was admitted to his local hospital with a diagnosis of an infection. Blood tests showed elevated liver enzymes, lymphocytosis and eosinophilia (ALT 1022 IU L^–1; bilirubin 64 μmol L^–1; INR 1·7; eosinophils 1·49 × 10⁹ cells L^–1; lymphocytes 9·58 × 10⁹ cells L^–1). Despite antibiotics, his condition deteriorated and he developed acute liver failure. He was transferred to the LITU at our centre. Examination revealed an urticated and purpuric papular exanthem with facial oedema and extensive lymphadenopathy. Skin biopsy revealed spongiosis, dermal oedema, perivascular infiltrate, red-cell extravasation and an inflammatory vascular reaction. A diagnosis of trimethoprim-induced DRESS was made. He was given IV methylprednisolone 250 mg on three consecutive days followed by a tapering course of oral prednisolone starting at 30 mg q24h. He was discharged from hospital 10 days after admission; his liver tests settled over the next 3 weeks. Unlike the other severe cutaneous adverse drug reactions, DRESS has a delayed onset following the initiation of the culprit drug, typically between 3 and 8 weeks. The disorder is often mistaken initially for an infective illness. Drug-induced liver injury is the most common systemic feature in DRESS; the mortality in DRESS (approximately 5%) is usually from acute liver failure. Trimethoprim alone is an unusual trigger for DRESS, whereas the sulfa moiety in sulfamethoxazole means that trimethoprim–sulfamethoxazole (Septrin) is a common cause of DRESS. Trimethoprim 300 mg q12h is used as a second-line antibiotic for acne. Based on our experience we would suggest that dermatologists should avoid this drug in the treatment of acne.