Clinical diagnosis and management of drug reaction with eosinophilia and systemic symptoms (DRESS) in children: An EAACI position paper.

Abstract

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but severe cutaneous adverse drug reaction encountered in both adults and children with a significant mortality rate. A number of guidelines or consensus reports have been published for optimal diagnosis and treatment of DRESS in adults, but none specifically for children. It is increasingly evident that there are significant differences in drug pharmacokinetics, metabolism, co-occurring infections, comorbidities, clinical manifestations, and severity of drug allergies between children and adults, as well as across different pediatric age groups.

Aim: This position paper aimed to evaluate and compare all the available data related to clinical features, diagnosis, and treatment of DRESS in adults and children in an attempt to identify the differences and gaps, and produce recommendations on diagnosis and treatment of this fatal disorder in children.

Materials and methods: A search of MEDLINE (via PubMed) and Web of Science from 2000 to 2024, including studies that assessed children with DRESS syndrome, was performed. In the absence of pediatric-specific data, studies involving adults or mixed populations (both adults and children) were also analyzed. Among a total of retrieved 5264 records, following duplicate removal and full-text assessment, a total of 493 manuscripts related to DRESS were included in the report and recommendation generation. The recommendations for the clinical diagnosis and treatment of DRESS in children were formulated in accordance with the directionality and strength guidelines suggested by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group and related research.

Results: Among retrieved records, there was only one randomized controlled trial, one meta-analysis, one systematic review, six retrospective comparative studies on treatment, and one systematic review on the accuracy of skin tests in DRESS. All of these studies were conducted in adults, rarely involving children, and none were exclusively performed in pediatric populations. Comparison of systematic case reviews revealed that some aspects of clinical features, prognosis, and mortality in children differed from those in adults. The diagnosis of DRESS is based on several clinical and laboratory criteria, which have been developed for adult patients but have not been validated for children. Causality assessment tools, in vivo skin tests, and in vitro tests have been used widely in adults to identify the culprit drugs in DRESS, while these tools are more rarely employed or reported in children. Adult guidelines or consensus reports recommend a severity-based, stepwise treatment approach for DRESS, whereas no such severity classification or treatment algorithms exist exclusively for children, leading to inconsistent management with numerous instances of overtreatment and undertreatment.

Conclusion: There is very limited evidence-based data on the diagnosis and management of DRESS both in adults and in children. Until more evidence becomes available, we propose a diagnostic algorithm, a DRESS severity classification, and a severity-based tailored treatment approach, all adapted to pediatric needs together with issued recommendations to enable physicians to provide better care and reduce morbidity and mortality in pediatric patients.