What is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome?

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Last updated: March 17, 2025View editorial policy

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From the Guidelines

DRESS syndrome is a severe, potentially life-threatening drug hypersensitivity reaction characterized by skin eruptions, fever, lymphadenopathy, hematologic abnormalities, and internal organ involvement, typically occurring 2-8 weeks after starting the offending medication, with a mortality rate of 10-20%.

Key Characteristics of DRESS Syndrome

  • It is a delayed T-cell–mediated reaction, which is much more dependent on the dose and concentration of the drug, as noted in the 2022 practice parameter update on drug allergy 1.
  • The syndrome involves skin eruptions, fever, lymphadenopathy, hematologic abnormalities, and internal organ involvement.
  • Common culprits include anticonvulsants (carbamazepine, phenytoin, lamotrigine), allopurinol, sulfonamides, and certain antibiotics.

Management and Treatment

  • Management primarily involves immediate discontinuation of the suspected drug and supportive care.
  • Systemic corticosteroids (typically prednisone 1-2 mg/kg/day) are the mainstay of treatment, with a slow taper over 2-3 months to prevent relapse, as the use of systemic corticosteroids can affect the timing and interpretation of testing for DRESS syndrome 1.
  • Severe cases may require hospitalization, particularly with significant organ involvement.

Testing and Diagnosis

  • The sensitivity of patch testing (PT) for DRESS syndrome is >50% for many drugs, but due to the risk of DRESS relapse, it is prudent to avoid PT or delayed intradermal testing (dIDT) until >6 months have elapsed from the acute reaction and/or the patient has been off systemic corticosteroid treatment for >1 month 1.
  • Delayed intradermal testing may be more convenient than PT for the patient and is more sensitive for certain delayed reactions, such as DRESS/drug-induced hypersensitivity syndrome (DIHS), particularly for antibiotic allergy and anticonvulsants 1.

Prevention and Follow-Up

  • Following recovery, patients should receive documentation of the reaction and avoid structurally similar medications in the future, as cross-reactivity is possible.
  • The pathophysiology involves delayed T-cell-mediated hypersensitivity and potential viral reactivation (particularly HHV-6), which can lead to confusion with skin testing results if performed too soon after the acute reaction 1.

From the Research

Definition and Characteristics of DRESS Syndrome

  • DRESS syndrome is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with anticonvulsants, sulfonamides, and allopurinol 2.
  • The reaction commonly manifests as a febrile skin eruption with lymphadenopathy and malaise between two and eight weeks following drug exposure 2, 3.
  • Internal organ involvement occurs in close to 90 percent of patients, and multiple organs may be involved in approximately half of those affected, most commonly the liver, kidney, and lung 2.

Clinical Features and Diagnosis

  • Clinical features include fever, morbilliform rash, eosinophilia, lymphadenopathy, and, in severe cases, multiorgan dysfunction, including interstitial nephritis, hepatitis, and pneumonitis 3, 4.
  • The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria is commonly used for diagnosis, with a score of 6 or more indicating definite DRESS syndrome 2, 4.
  • Comprehensive history taking and accurate reconciliation of active and recent medications are necessary to make the diagnosis, as DRESS syndrome poses unique diagnostic challenges due to its similarity to other cutaneous reactions and the delay between drug exposure and symptom onset 3, 5.

Treatment and Management

  • Immediate withdrawal of the culprit drug and administration of systemic corticosteroids is the most widely accepted treatment 6, 5.
  • Supportive care and topical or systemic glucocorticoids remain the treatment standards, with additional options including cyclophosphamide, cyclosporine, intravenous immunoglobulin, and N-acetylcysteine 6, 5.
  • Early recognition and intervention are vital for preventing severe complications, and healthcare providers must be vigilant when evaluating patients presenting with fever and rash 3, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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