Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Associated with Enoxaparin Therapy in a Pediatric Patient

Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare drug hypersensitivity reaction characterized by diffuse skin eruption with systemic symptoms (fever, lymphadenopathy, elevated transaminases, leukocytosis with eosinophilia and atypical lymphocytes) which develops 2-6 weeks after exposure to inciting medications. Clinical presentation is variable and nonspecific. DRESS syndrome is more common in adults, can be life threatening, and is most commonly seen with antibiotics, antiepileptic drugs, and allopurinol. An inciting drug is identified in the majority of cases. DRESS syndrome has been described rarely in association with Vitamin K antagonists and direct oral anticoagulants. 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. We present a case of a pediatric patient with DRESS syndrome associated with enoxaparin therapy.

Case Report: A previously healthy 11-year-old female was admitted with sepsis secondary to osteomyelitis and periosteal abscess of the left lower extremity, as well as MRSA bacteremia. The patient was initiated on clindamycin and vancomycin for treatment of underlying infections. A left lower extremity ultrasound with doppler was obtained due to lower extremity swelling and demonstrated an acute deep venous thrombus of the left popliteal vein. She was initiated on a heparin drip and subsequently transitioned to enoxaparin one week later. Several weeks into her hospital course (two weeks after initiation of enoxaparin), she developed facial swelling, a generalized morbilliform rash, and diffuse lymphadenopathy both on exam and abdominal imaging. She continued to have persistent fevers despite multiple washouts of the extremity, appropriate antimicrobial coverage, and negative blood cultures. Liver enzymes concurrently increased (AST 362 IU/L (normal 5-60 IU/L), ALT 371IU/L (normal <35 IU/L) at peak) with development of clinical symptoms. Eosinophilia was not present on initial CBC, though she subsequently developed mild eosinophilia (1.1 K/ul at peak). HHV6, CMV, and EBV serologies were all negative. Skin biopsy was performed and was consistent with a drug eruption. Using the RegiSCAR criteria for DRESS syndrome, this constellation of labs and symptoms indicate a definite case of DRESS syndrome with a score of 6 (final score >5 is needed for a definite case). The patient was started on treatment with high-dose steroids. Clindamycin and vancomycin were both discontinued due to their known association with DRESS syndrome. She was transitioned to doxycycline, however, no improvement in rash, fevers, or liver enzymes was seen over the course of five days. Given this, enoxaparin was transitioned to apixaban. The patient improved with resolution of rash, fevers, and improvement of liver enzymes and eosinophilia within a few days of the discontinuation of enoxaparin.

Conclusion: 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, and therefore requires a high index of suspicion. Though children with DRESS syndrome have a better prognosis than adults, prompt recognition and treatment is required to limit morbidity and mortality. In pediatric patients receiving treatment with enoxaparin, DRESS syndrome should be included on the differential for those who develop persistent fevers, lymphadenopathy, rash, transaminitis and/or eosinophilia, and discontinuation of enoxaparin should be considered.