Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) by Melissa Charbonneau

 Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced idiosyncratic hypersensitivity reaction that occurs approximately 2-8 weeks after offending drug exposure. This reaction can occur even after discontinuation of the offending drug, due to prolonged latency.

Incidence: 216 cases of DRESS have been reported between 1985 and 2000, with a current estimated incidence of 1 per 5000. Mortality rates are close 10 percent.

Presentation: DRESS presents as a mild to severe hypersensitivity reaction with cutaneous and systematic symptom involvement. Infected patients most often present with eurticaria and fever, with possible eosinophilia, lymphocytosis, and lymphadenopathy. Cutaneous reactions such as bullae, pustules, purpura, lesions, and facial edema may also occur. In more severe cases, organ failure can occur in the liver, lung and kidneys. Abnormal laboratory findings include: elevated liver enzymes, leukocytosis with eosinophil counts, increased alanine aminotransferase, HHV-6 infection, and elevated WBC.

Pathogenesis: Causation of DRESS syndrome is not fully understood, but the following indications have been evaluated:

    • Patients with the HLA-B*1502 genotype may be more prone to hypersensitivity reactions (such as DRESS or Stevens – Johnson syndrome). Medications such as allopurinol and carbamazepine may induced such reactions in this patient population.
    • A virus-drug interaction may occur, leading to viral reactivation. Viral reactivation may be caused by DRESS releasing drug specific T-cells into the blood. Drugs such as lamotrigine and carbamazepine may induced viral reactivation in this patient population. The most commonly seen viral reactivations are HHV-6. HHV-&, EBV, and cytomegalovirus.
  • Some common offending DRESS drugs with clinical manifestations: lamotrigine, phenytoin, allopurinol, minocycline, carbamazepine, valproic acid, and abacavir.

Diagnosis: Similar drug-induced conditions (i.e. Steven-Johnsons syndrome) should be ruled out before proceeding to run additional diagnostic procedures. The latency period, presentation of symptoms and laboratory findings should be utilized as differential diagnostic criteria. The following labs can be drawn to assist with differential diagnosis: liver enzyme test, complete blood count, serology of viral hepatitis, SCR and urinalysis, skin biopsy, HHV-6 test, serology for viral hepatitis.

The following tools can be utilized to assist in diagnosis:

  • RegiSCAR criteria for DRESS: patient must exhibit three out of four started criteria to be diagnosed with DRESS: Hospitalization, reaction to suspected drug, acute rash, fever >38° C*, at least 2 sites of enlarged lymph nodes*, involvement of at least 1 internal organ*, WBC abnormalities*, lymphocytes abnormalities, eosinophil abnormalities, platelet count abnormalities.
  • Japanese Group Criteria for DRESS: patient must exhibit at least 7 of the criteria to be diagnosed with DRESS: maculopapular rash, fever >38° C, liver abnormalities, leukocyte abnormalities, leukocytosis (>11 X 109/L), atypical lymphocytosis, eosinophilia (>1.5 x 109/L), HHV-6 reaction, and lymphadenopathy.

Management and Treatment: Swift discontinuation of offending agent should be the first step of managing DRESS. The earlier the drug discontinuation, the better the prognosis. Avoid adding other medications on board at this time. If the patient is on antiepileptic agents, valproic acid and carbamazepine should be substituted for less offending agents. Supportive care for management of symptoms would be the next step. Topical corticosteroids are often used for skin irritation, lesions, pruritus and inflammation. Systemic corticosteroids are also used for patients with organ involvement, though rapid tapering should be avoided, due to risk of DRESS relapse. Antiviral agents, such as ganciclovir, foscarnet and cidofovir can be used to prevent reactivation of HHV-6 and cytomegalovirus. Management should continue until symptoms resolve.

Sources:

  1. Dewan AK, Quinonez RA. Allopurinol-Induced DRESS Syndrome in PatientS. Pediatric Dermatology. 2009;27(3):270-273. doi:10.1111/j.1525-1470.2009.00983
  2. Velasco MJ, Mcdermott J. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. International Journal of Dermatology. 2013;53(4):490-493. doi:10.1111/j.1365-4632.2012.05547