A 19-year-old female with a past medical history of epilepsy presented to the emergency department for evaluation of rash and fever. Two days prior to presentation she began to experience fevers with a Tmax of 103°F. One day before presentation she developed a rash that began on her face and slowly spread down her body, now involving her palms. The patient endorsed associated pruritus and cervical lymphadenopathy with the rash. The patient specifically denied mucous membrane involvement (mouth, eyes, genitalia), vomiting, diarrhea, dysuria, hematuria, neck stiffness, cough, dyspnea, chest pain, or exposure to ticks or exotic animals. Of note, she reported that her dose of lamotrigine has been slowly uptitrated, most recently two days prior changing from 50 mg BID to 75 mg BID.

Vitals: T 39.6°C; HR 140; BP 102/66; RR 15; O2 sat 97% on RA

General: Alert and oriented, well-developed female in no acute distress

Cardiovascular: Tachycardia, regular rhythm

HEENT: Bilateral cervical lymphadenopathy; facial edema; conjunctiva clear; oral mucous membranes clear

Skin: Deeply erythematous/papules coalescing into plaques diffusely on the face, trunk, extremities; no pustules, purpura, or vesicles/bullae noted; no scales or desquamation

Complete Blood Count (CBC): WBC 9.84 (eosinophils 7%), Platelets 144

Alkaline phosphatase (ALP): 180

ALT: 378

AST: 228

C-reactive protein (CRP): 91

Urine protein: 11 mg/dL

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is an idiosyncratic, potentially fatal, adverse drug reaction to anticonvulsants, antimicrobials, antivirals, or allopurinol with a multifactorial pathogenesis. It has a delayed onset, typically within 2-8 weeks, after drug initiation. Clinical presentation can be diverse but is usually characterized by a diffuse skin rash, fever, lymphadenopathy, eosinophilia, and internal organ involvement (most commonly the liver). Incidence ranges from 1 in 1,000 to 1 in 10,000 with a mortality rate that can be as high as 10%, and is commonly related to fulminant hepatitis. Diagnosis can be extremely challenging due to the variability in clinical presentation. The regiSCAR diagnostic criteria is the most used diagnostic criteria and is based on a scoring system for possible, probable, or definite diagnosis.

Immediate discontinuation of the offending medication is critical. Symptoms may continue for several weeks after withdrawal of the inciting agent. The mainstay of treatment is systemic corticosteroids with tapering over a long period. Other immunosuppressants may be used in refractory cases. If DRESS syndrome occurs in the setting of an aromatic anticonvulsant, the patient should not be started on any other aromatic anticonvulsants due to their cross-reactivity.

Take-Home Points

  • DRESS syndrome is a severe, possible life-threatening adverse drug reaction that is frequently overlooked and missed because of its variable clinical presentation. Increasing familiarity with its clinical presentation is of utmost importance for recognition and treatment.
  • The inciting agent (aromatic anticonvulsant, antimicrobial, allopurinol, etc.) should be stopped immediately and should not be restarted at any time. Corticosteroids are the mainstay of treatment with gradual tapering over multiple months.
  • Cho YT, Yang CW, Chu CY. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System. Int J Mol Sci. 2017 Jun 9;18(6):1243. doi: 10.3390/ijms18061243. PMID: 28598363; PMCID: PMC5486066.
  • Choudhary S, McLeod M, Torchia D, Romanelli P. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. J Clin Aesthet Dermatol. 2013 Jun;6(6):31-7. PMID: 23882307; PMCID: PMC3718748.

Alicia Hereford, MD

Alicia Hereford, MD

Resident Physician
Department of Emergency Medicine
UAB Medical Center
Alicia Hereford, MD

Latest posts by Alicia Hereford, MD (see all)

Matthew Heimann, MD

Matthew Heimann, MD

Assistant Professor
Department of Emergency Medicine
University of Alabama at Birmingham
Matthew Heimann, MD

Latest posts by Matthew Heimann, MD (see all)