Recognizing lamotrigine as a known trigger of cutaneous adverse events, we identified DRESS syndrome as the best fitting diagnosis. Our patient met the RegiSCAR inclusion criteria, and the corresponding scoring system classified the case as a probable manifestation of DRESS [1]. After comprehensive exclusion of differential diagnoses, we were therefore able to confirm the diagnosis.

The prevalence of kidney involvement in DRESS-syndrome differs considerably, ranging between 13 and 35% of cases with internal organ damage [2]. Kidney failure in DRESS syndrome is generally due to AIN (classic triad: rash, eosinophilia, fever) [2], yet the precise etiology remains uncertain. The suspected pathomechanism of drug-induced AIN and, interestingly, also DRESS, involves an idiosyncratic delayed type IV hypersensitivity reaction. It is initiated by the formation of haptens, which provoke a cellular immune response, either through direct cellular damage or through the release and deposition of antibodies [3]. DRESS and AIN have previously been described as distinct clinical entities, despite their shared symptoms such as fever, rash, and a suspected common etiology. We therefore propose to establish a common definition for a drug-induced syndrome involving kidney damage, ideally based on its etiology.

In our case, histological examination revealed interstitial nephritis along with tubular necrosis, confirming severe AIN with a tubular necrotic component, consistent with findings in other DRESS cases with renal involvement [2], (see Fig. 1).

AIN and DRESS, in contrast to ATN, are considered to be dose-independent [2]. However, in our patient we suspect that non-adherence to prescribed doses of antiepileptic drugs, resulting in inconsistent and temporarily elevated drug levels, contributed to kidney failure. For lamotrigine, the risk of rash has been reported to increase if the initial dose or dose escalation rate is exceeded. Here, both applied [4].

In the absence of controlled studies, treatment recommendations for DRESS are based on empirical and consensus-based approaches using mainly systemic corticosteroids tapered over 3 months. Long-term prognosis has not been reported systematically.

The initially normal drug levels of lamotrigine were misleading in the diagnostic process. This report aims to raise awareness of the prevalent risks of treatment non-adherence in the pediatric population. Approximately 50% of children are reported not to adhere to treatment regimens, a number that tends to increase in adolescence [5].