Discussion
The diagnosis of DRESS syndrome can be challenging due to its nonspecific presentation, particularly in pediatric patients where symptoms can overlap with common viral syndromes and Kawasaki disease. The first presenting symptoms typically involve fever and a maculopapular rash. Patients then develop lymphadenopathy and hematologic abnormalities, including leukocytosis with eosinophilia and atypical lymphocytes, as well as transaminitis.5Symptoms develop 2-6 weeks following exposure to an inciting drug and can also be triggered by viruses most commonly HHV6, as well as EBV and CMV.1,5 The RegiSCAR is used to identify DRESS syndrome given the diagnostic uncertainty. The criteria includes a combination of symptoms (rash, fever, lymphadenopathy), laboratory findings (atypical lymphocytes, eosinophilia, elevated liver enzymes), biopsy results, duration of symptoms, and exclusion of other diagnosis (Table 1).1,5 A score of 2-3 indicates possible, 4-5 indicates probable, and greater than 5 indicates a definite case of DRESS syndrome.1,5
If left untreated, given its multisystem involvement, DRESS syndrome can result in multi-organ failure and significant morbidity and mortality, with a 10% mortality rate.1 A high index of suspicion is therefore required in order to prevent both short- and long-term complications, especially as immediate discontinuation of the offending medication is vital to control the disease.
The most common inciting drugs include antiepileptics (carbamazepine, phenytoin, phenobarbital), antibiotics (Bactrim, clindamycin, vancomycin), and allopurinol.1,5 DRESS syndrome has been described rarely in association with Vitamin K antagonists and direct oral anticoagulants in adult patients.2,3,4 In an in-depth examination of existing literature, there are only two reported cases of DRESS syndrome associated with enoxaparin therapy, both in adult patients, and no reports of pediatric DRESS syndrome secondary to anticoagulants. Rates of venous thromboembolism requiring treatment with anticoagulation have been increasing overall in the general pediatric population. This is especially true in the wake of the COVID-19 pandemic and increasing inflammatory syndromes in children post-infection. Enoxaparin is a widely used anticoagulant in the pediatric population. As such, general pediatricians, as well as specialists, should be comfortable with identifying and managing the complications associated with it. DRESS syndrome should be included on the differential for any patient on enoxaparin who develops rash, fevers, lymphadenopathy, and eosinophilia. Similarly, enoxaparin should be considered as a possible causative agent in patients diagnosed with DRESS syndrome.