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.