Acute interstitial nephritis and DRESS syndrome without eosinophilia associated with cefepime.

Qadri I, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-221401 Description The drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is a potentially life-threatening drug-induced reaction characterised by a severe skin eruption, fever, haematological abnormalities (eosinophilia or atypical lymphocytes) and internal organ involvement (liver is the most common). These manifestations are thought to be a type IV hypersensitivity with a delayed onset of usually 2–6 weeks after the initiation of drug therapy. 2 While the pathogenesis of this condition is not well understood, mechanisms such as detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation and reactivation of Epstein-Barr virus and human herpesvirus 6 and 7 have been proposed. The most common drugs associated with DRESS syndrome are the aromatic anticonvulsants (phenytoin, phenobarbital, carbamazepine) and sulfonamides. A 62-year-old man with poorly controlled diabetes and subacute osteomyelitis presented to the hospital with fatigue, fever and anorexia. Prior to admission, he was being treated for osteomyelitis as an outpatient for approximately 6 weeks with vancomycin 1 g intravenously every 12 hours and cefepime 6 g intravenous continuous infusion daily. Physical examination revealed tender axillary lymphadenopathy and a morbilliform, blanchable rash present on his flank and extremities (figure 1). Laboratory evaluation revealed leucocytosis, transaminitis and acute kidney injury with a serum creatinine of 3.6 mg/dL (baseline 0.8 mg/dL). Peripheral smear demonstrated atypical lymphocytes and vacuolated neutrophils, but there was no eosinophilia. Urine microscopy revealed white blood cell (WBC) casts without eosinophiluria. Serum complements were normal and hepatitis panel was negative. Renal biopsy demonstrated acute interstitial nephritis (AIN) and skin biopsy showed vacuolar interface dermatitis with a mixed dermal infiltrate (figure 2). He was diagnosed with DRESS syndrome based on a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score of 6 and AIN. Empiric steroid therapy was started with prednisone 1 mg/kg/day. Though he required renal replacement therapy for a few days, his renal function recovered subsequently (figure 3). His rash and transaminitis improved as well. While both vancomycin and cefepime have been implicated in the causation of DRESS syndrome, we believe cefepime is the major culprit in this case because of the high dose used. Moreover, his vancomycin trough levels were never high. Acute interstitial nephritis and DRESS syndrome without eosinophilia associated with cefepime Irfan Qadri, Xu Zeng, Ruifeng Guo, Abhilash Koratala Images in...