Antiepileptic drugs

Abstract

Haemophagocytic lymphohistiocytosis secondary to drug reaction with eosinophilia and systemic symptoms: case report A 49-year-old man developed haemophagocytic lymphohistiocytosis (HLH) secondary to drug reaction with eosinophilia and systemic symptoms (DRESS) during treatment with levetiracetam, phenytoin, sodium valproate, midazolam and clobazam for refractory seizures. The man was transferred to the ICU from a local hospital due to a spontaneous intracranial bleed requiring neurosurgical intervention. There was no past medical history and he was not taking any regular medication. He subsequently developed refractory seizures. He was therefore initiated on levetiracetam, phenytoin, sodium valproate, midazolam infusion and clobazam [dosages not stated; not all routes stated]. The admission was complicated by a pneumonia. He was therefore initiated on vancomycin and piperacillin/tazobactam. Vancomycin and piperacillin/tazobactam were subsequently switched to meropenem. On day 25 of admission, he developed a morbilliform rash on the torso and limbs, generalised oedema and persistent fever. Laboratory investigations revealed elevated eosinophil count, increased ALT and declining renal function. A CT scan revealed prominent, mildly enlarged mediastinal, axillary, pelvic and inguinal lymph nodes, up to 16mm in diameter. Based on the RegiSCAR score of 7, a definite diagnosis of DRESS was made. The diagnosis of DRESS was further supported by skin biopsy findings of a perivascular lymphocytic inflammatory infiltrate with interstitial eosinophils and intraluminal neutrophils. A viral reactivation screening (EpsteinBarr virus, human herpesvirus 6, Human herpesvirus 7, HIV, hepatitis B virus and hepatitis C virus) was found to be negative. The man’s anti-epileptic medications were felt to be the most likely responsible drugs for causing DRESS, and all were stopped apart from the midazolam infusion. Prednisolone 60mg daily was initiated, but his condition continued to deteriorate over the next 48h, with persistent high fever and the development of erythroderma and multi-organ failure (ALT 3749 U/L, creatinine 405 μmol/L and reduced consciousness level). Sepsis was initially considered but repeated microbiology samples were negative, and there was lack of response to broad-spectrum antibiotics [specific drug not stated]. A diagnosis of HLH, felt to be secondary to the initial DRESS, was then considered following consultation with rheumatology and haematology. The diagnosis of HLH was supported a highly elevated serum ferritin of 88 322 μg/L, low fibrinogen and increased triglycerides. Bone marrow biopsy was performed which confirmed the presence of haemophagocytosis. The H-score was 227 points, conferring a 96% probability of haemophagocytic syndrome. He was treated with dexamethasone and anakinra, following which a gradual clinical and biochemical improvement was observed. He was discharged from the ICU after a further 3 weeks.