Drug reaction with eosinophilia and systemic symptoms

Last updated: March 18, 2022

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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening adverse drug reaction caused by delayed hypersensitivity to medication (most commonly anticonvulsants or antimicrobials). Risk factors include immunosuppression, human herpesvirus-6 (HHV-6) infection, and pharmacogenetic susceptibility. DRESS is characterized by delayed onset (2–8 weeks after drug exposure), waxing and waning symptoms, and a prolonged course. Symptoms typically include fever, diffuse rash, facial edema, lymphadenopathy, and internal organ involvement. Peripheral blood eosinophilia is common but not universally observed. Diagnosis is based on medication history, physical exam, blood tests, and skin biopsy. Management typically involves prompt withdrawal of all possible triggering agents, supportive care, and guidance from specialists for any affected organ. Patients should be carefully monitored for internal organ involvement and complications. The liver is the most commonly affected organ, usually with asymptomatic hepatic inflammation; necrosis and liver failure are also possible and the leading cause of death from DRESS.

The pathogenesis of DRESS is not completely understood. Potential mechanisms include: [1]

Clinical manifestations in DRESS have a delayed onset (typically 2–8 weeks) after exposure to the offending agent. In rare cases in which a patient who has recovered from DRESS is reexposed to the triggering agent, the symptom onset is much faster (hours or days). [4]

The key features of DRESS are fever, diffuse skin lesions, and symptoms of internal organ involvement. [1][4][6]

Symptoms in DRESS usually manifest 2–8 weeks after drug exposure and often have a protracted clinical course with waxing and waning of symptoms even after the triggering agent is withdrawn. [1][4][6]

Approach [4][7]

  • Consider DRESS in patients with suggestive clinical features (e.g., fever, diffuse rash).
  • Obtain a detailed history, with emphasis on the following:
    • Medications and supplements started within the last 2–8 weeks
    • Family history of drug-induced SCARs
  • Obtain laboratory studies and a skin biopsy.
  • Assess for internal organ involvement.
  • Confirm diagnosis using a validated score (e.g., RegiSCAR).

Early diagnosis is critical to reducing morbidity and mortality, although death can occur even with proper management. [4]

Laboratory studies [4]

Skin biopsy [4][8]

Biopsy findings in DRESS are typically nonspecific and therefore not required for diagnosis.

Biopsy is not required for diagnosis; findings in DRESS are typically nonspecific, so the procedure is most helpful for ruling out other etiologies of rash.

Evaluation for internal organ involvement [2]

The majority of patients (∼ 90%) have involvement of at least one organ/system, most commonly hepatic inflammation. Evaluate all patients for liver and kidney injury and consider other tests depending on the presence of clinical or laboratory features suggestive of involvement of other organs.

Diagnostic criteria [2][4]

RegiSCAR scoring system for diagnosing DRESS syndrome [2][4]
Add 1 point for each Reduce 1 point for each


(max of 3 points)

  • Lymph node enlargement
  • Rash characteristic of DRESS
  • Rash covers > 50% of body surface area
  • Fever < 38.5°C
  • Rash not characteristic of DRESS
  • Resolution in < 15 days

Diagnostic studies

(max of 5 points)

  • Atypical lymphocytes
  • Eosinophils 700–1,500/mm3 (add 2 points if ≥ 1,500/mm3)
  • Organ involvement (1 organ affected = 1 point; ≥ 2 organs affected = 2 points)
Exclusion of other potential causes
  • ≥ 3 other causes have been excluded
  • n/a

Total Score

  • < 2: Excluded
  • 2–3: Possible
  • 4–5: Probable
  • > 5: Definite

Approach [4]

  • Stop all suspected offending agents immediately (i.e., drug withdrawal).
  • Determine severity based on internal organ involvement [4][9]
    • Nonserious DRESS: No organ involvement, OR AKI stage 1, OR mild liver injury
    • Serious DRESS: AKI stage 2 and above, OR moderate to severe liver injury , OR involvement of other organs
  • Start corticosteroids (topical or systemic based on severity).
  • Provide supportive care as needed.
  • Post-acute recovery: Consider referral to an allergist and monitoring for autoimmune sequelae. [4][7]

Withdrawal of all suspected triggering medications is the cornerstone of management for patients with suspected DRESS. Delays in medication withdrawal are associated with a prolonged course and worse prognosis. [4]

Avoid empiric NSAIDS and empiric antibiotics (especially amoxicillin) during the acute period as they may prolong or worsen the course. [4]

Nonserious DRESS [4]

  • Admit all patients with nonserious DRESS to acute care. [4]
  • Start therapy with topical corticosteroids (high or very high potency, e.g., clobetasol ). [4]
  • Monitor for progression to serious DRESS and escalate therapy if needed.
    • Evaluate for clinical signs and symptoms of organ involvement daily.
    • Trend baseline laboratory parameters at least every 72 hours.

Serious DRESS [4]

  • Admit all patients with serious DRESS.
    • Severe organ involvement: Consider ICU admission.
    • Severe cutaneous involvement : Consider admission to a burn unit.
  • Requires multidisciplinary management; consult specialists for affected organs.
  • Perform clinical and laboratory monitoring for new or worsening organ involvement at least every 24 hours.
  • Start pharmacological treatment in consultation with a specialist.

Liver failure secondary to hepatic necrosis is the leading cause of death from DRESS. For patients with severe liver injury, consult hepatology early to evaluate for liver transplant candidacy. [4]

Supportive care

  • DRESS is fatal in ∼10% of cases. [4]
  1. Cabañas R, Ramírez E, Sendagorta E, et al. Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome. J Investig Allergol Clin Immunol. 2020; 30 (4): p.229-253. doi: 10.18176/jiaci.0480 . | Open in Read by QxMD
  2. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part I. Clinical perspectives. J Am Acad Dermatol. 2013; 68 (5): p.693.e1-693.e14. doi: 10.1016/j.jaad.2013.01.033 . | Open in Read by QxMD
  3. Kardaun SH, Mockenhaupt M, Roujeau J-C. Comments on: DRESS syndrome. J Am Acad Dermatol. 2014; 71 (5): p.1000-1000.e2. doi: 10.1016/j.jaad.2013.11.053 . | Open in Read by QxMD
  4. Phillips EJ, Chung W-H, Mockenhaupt M, Roujeau J-C, Mallal SA. Drug hypersensitivity: Pharmacogenetics and clinical syndromes. J Allergy Clin Immunol. 2011; 127 (3): p.S60-S66. doi: 10.1016/j.jaci.2010.11.046 . | Open in Read by QxMD
  5. Dean L, Pratt VM, Scott SA, et al. Abacavir Therapy and HLA-B*5701 Genotype. Medical Genetics Summaries [Internet]. 2012 .
  6. Cho Y-T, Yang C-W, Chu C-Y. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System. Int J Mol Sci. 2017; 18 (6): p.1243. doi: 10.3390/ijms18061243 . | Open in Read by QxMD
  7. Isaacs M, Cardones AR, Rahnama-Moghadam S. DRESS syndrome: clinical myths and pearls. Cutis. 2018; 102 (5): p.322-326.
  8. Cardones AR. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Clin Dermatol. 2020; 38 (6): p.702-711. doi: 10.1016/j.clindermatol.2020.06.008 . | Open in Read by QxMD
  9. Aithal GP, Watkins PB, Andrade RJ, et al. Case Definition and Phenotype Standardization in Drug-Induced Liver Injury. Clinical Pharmacology & Therapeutics. 2011; 89 (6): p.806-815. doi: 10.1038/clpt.2011.58 . | Open in Read by QxMD

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