Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in childhood: a narrative review

Abstract

Despite being rare, the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a serious, possibly fatal condition that may affect both adults and children who may be also burdened by delayed sequelae. It is an adverse drug reaction characterized by widespread skin involvement, fever, lymphadenopathy, visceral involvement, and laboratory abnormalities (eosinophilia, mononucleosis-like atypical lymphocytes). It is more frequently triggered by anticonvulsants, sulphonamides, or antibiotics, the latter being responsible for up to 30% of pediatric cases. The disease typically develops 2-8 weeks after exposure to the culprit medication, with fever and widespread skin eruption; mild viral prodromes are possible. Unfortunately, diagnosis is challenging due to the absence of a reliable test; however, a score by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) allows to classify suspect patients into no, possible, probable, or definite DRESS cases. Moreover, rapid-onset DRESS syndrome has been described in recent years. It affects children more often than adults and differs from the most common form because it appears ≤15 days vs. >15 days after starting the drug, it is usually triggered by antibiotics or iodinated contrast media rather than by anticonvulsants and has a higher presence of lymphadenopathy. Differential diagnosis between rapid-onset antibiotic-driven DRESS syndrome, viral exanthems, or other drug eruptions may be challenging, but it is mandatory to define it as early as possible to start adequate treatment and monitor possible complications. The present review reports the latest evidence about the diagnosis and treatment of pediatric DRESS syndrome.

Keywords: DRESS; antibiotics; anticonvulsants; children; drug hypersensitivity; drug reaction; drug reaction with eosinophilia and systemic symptoms.

Figure 1

Pathogenesis of the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Incomplete drug metabolism and the accumulation of reactive metabolites can lead to a robust and delayed immunological reaction, stimulating drug-specific T lymphocytes in people with predisposing genetic factors and producing the systemic effects and the clinical presentation of the DRESS syndrome. In some patients, a viral reactivation may be detected between 2 and 4 weeks after symptoms onset. It results from a direct effect of the culprit drug or an immunodeficiency state caused by the anti-drug responses and may induce antiviral responses that contribute to the development of the systemic effects. The dotted line indicates possible cofactors whose exact role in the pathogenesis of DRESS is yet to be fully elucidated. Ig, immunoglobulins; p.i., pharmacological interactions; IL, interleukin; TARC, thymus and activation regulated chemokine; TNF-α, tumor necrosis factor α; IFN-γ, interferon γ.

Figure 2

Comparison between adult and pediatric Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome with reference to epidemiology (11), mortality rate (4), culprit drug (1, 19), onset of symptoms (8), pathogenesis (11), clinical manifestations (11, 38), and long-term sequelae (9, 44). MDH, Multiple Drug Hypersensitivity.

Figure 3

A therapeutic approach to the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome based on current scientific evidence. The red dotted line indicates possible therapeutic options, on which further studies and evidence are needed. Since there is no consensus on the therapeutic treatment of pediatric DRESS syndrome, the therapeutic options in the dotted boxes are listed in alphabetical order. * Studies available in the literature currently concern only adult patients with DRESS syndrome. ° Studies available in the literature regarding pediatric DRESS syndrome. ^δ Corticosteroids slow tapering (over 3–6 months). IVIG, intravenous immunoglobulins; IL-5, interleukin-5; IL-5-R, IL-5 receptor.