Correct!
6. All of the above
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is defined by the presence of at least three of the following findings: fever, exanthema, eosinophilia, atypical circulating lymphocytes, lymphadenopathy, and hepatitis. It is a severe drug hypersensitivity reaction with cutaneous, hematological and multi-organ involvement (1-4). Hemodynamic instability is seen and can be mistaken for septic shock. Estimated mortality rate is high at 10%. Patients typically present with extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes. Onset is typically 2-6 weeks after exposure to a medication. The most common visceral manifestation is acute hepatitis. Other organ system involvement can include myocarditis, colitis, encephalitis and rarely interstitial pneumonia with eosinophilia. Fulminant hepatic failure is the leading cause of death.
Stevens Johnson syndrome and toxic epidermal necrolysis are a spectrum of the same condition with toxic epidermal necrolysis affecting 30% of more of the skin and Stevens Johnson less than 10%. These cause necrosis of the epidermis and sloughing of the mucous membranes and skin. Urticaria with angioedema is a pruritic raised area of the skin with swelling of dermis and subcutaneous tissue sometimes leading to anaphylaxis. Pemphigus is a bullous disease of autoimmune cause with autoantibodies to desmogleins. It can be associated with drug exposure, causes sloughing of the epidermis and may involve mucous membranes (5). These all can be life-threatening.
Hospital Course (cont’d)
A dermatology consult was obtained for this suspected drug reaction. The consensus was that the presence of persistent fever, and generalized rash with a systemic inflammatory response was likely due to a drug reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome). It was thought that the culprit drug was either piperacillin/tazobactam or vancomycin.
Exact pathogenesis of DRESS is unknown, but may involve failure of drug detoxification pathways or reactivation of human herpes viral infections. In some studies, HHV-6 reactivation has been suggested as a potential contributor with the virus detected in 41% of cases; and in one prospective study including 40 DRESS patients, Epstein-Barr virus, HHV-6, and HHV-7 reactivations were found in 76% of the cases. It has been shown that there is a drug-induced hypogammaglobulinemia that occurs in DRESS syndrome permitting viral reactivation of HHV-6, HHV-7, EBV, and CMV and this results in oligoclonal proliferation of activated virus-specific and nonspecific T cells (6). Eosinophilic accumulation is thought to account for the multi-organ involvement.
What is the first step of recommended therapy for severe drug reactions such as DRESS syndrome? (click on the correct answer to proceed to the last panel)