Medical Student University of Toronto Temerty Faculty of Medicine Toronto, Ontario, Canada
Background: Drug reaction with eosinophilia and systemic symptoms (DReSS) is a severe adverse drug reaction characterized by fever, skin rash, lymphadenopathy, hematological abnormalities, and internal organ manifestations, typically 2-8 weeks after starting treatment. While the condition is known to cause mortality and long-term sequelae, pediatric data is limited to case reports and small systematic reviews. In addition, there are no established clinical practice guidelines for managing children with DReSS. Objective: We aimed to review the available data on pediatric DReSS to (1) identify current treatment strategies, (2) determine mortality, and (3) study long-term sequelae. Design/Methods: We conducted a scoping review based on an extensive search strategy that yielded 8,279 unique publications. Full-text screening was conducted for 2,641 titles and included if they involved (1) DReSS, (2) age < 18 years at diagnosis, and (3) written in English, French, Spanish, Dutch, or German. Extracted data included patient demographics, causative drug(s), clinical presentation, organ involvement, treatment details, survival, cause of mortality, and long-term sequelae. Results: In total, 644 individual patients were identified from 265 case reports and 34 cohort studies. The mean age at diagnosis was 9.5 years (IQR 5-14 years; 52% male). Cases presented with a combination of skin rash (99%), fever (99%), lymphadenopathy (68%), and internal organ involvement (94%), in particular liver (87%), respiratory tract (26%), and kidney (15%). Anti-epileptics and antibiotics were the most commonly associated culprits. Following drug withdrawal (100%), management strategies included, either alone or in combination, systemic corticosteroids (75.6%), intravenous immunoglobulins (10.4%), and cyclosporine (1.4%). Corticosteroids were administered orally or intravenously in doses varying from 0.5-30 mg/kg/dose. Supportive therapy alone was used in 21.4%. Disease flare occurred in 6.8% of cases, usually associated with corticosteroid tapering. During a median follow-up of 4 months (IQR = 1.5–9 months), autoimmune sequelae were reported in 3.7% of patients. The mortality rate was 3%, most commonly from multi-organ failure.
Conclusion(s): This study supports an urgent need to develop clinical practice guidelines for the management of pediatric DReSS to address the high mortality rate, inconsistent management practices, and lack of long-term follow-up of survivors.
