Clinical Pearls & Morning Reports
Published October 19, 2022
DRESS (drug reaction with eosinophilia and systemic symptoms) is a severe cutaneous adverse reaction to a medication, with a mortality rate of approximately 10%. DRESS is typically characterized by a constellation of findings, including fever, lymphadenopathy, eosinophilia, rash, atypical lymphocytes, and multiorgan involvement; however, the presentation is highly variable, and not all features are present in every patient. Read the NEJM Case Records of the Massachusetts Hospital here.
Q: What is the leading cause of death among patients with DRESS?
A: Although liver involvement is the leading cause of death among patients with DRESS, cardiac involvement is the second leading cause owing to the infiltration of eosinophils into the myocardium. DRESS with eosinophilic myocarditis portends a poor prognosis with a high mortality rate and no clear treatment standard.
Q: When does DRESS typically manifest in a patient with continuous exposure to an offending medication?
A: Medications that are common triggers of DRESS include antibiotic agents, anticonvulsant agents, and antituberculous therapies, among others. DRESS typically manifests 2 to 8 weeks after continuous exposure to the offending medication, and downstream consequences are hypothesized to be related to the reactivation of human herpesvirus 6 (HHV-6). As such, HHV-6 viral load testing is sometimes performed in borderline cases. Skin biopsy may suggest a drug hypersensitivity reaction, but there are no specific histopathological findings that confirm a diagnosis of DRESS.
A: Although the typical treatment for DRESS is systemic glucocorticoid therapy, clinical trial data supporting the efficacy of such treatment, along with the appropriate dose and duration of treatment, are lacking. Occasionally, alternative immunosuppressive agents may be used, particularly in patients at high risk for infectious complications. Intravenous immune globulin (IVIG) has been shown to have a beneficial effect in select DRESS cases, although an open-label study showed a high risk of adverse events and the need for a high proportion of the patients to switch to oral glucocorticoids. IVIG treatment is also associated with a large volume load and therefore may not be ideal for use in patients with renal failure or heart failure.
A: The specific mechanism by which IVIG treats DRESS is not known but is related to its immunomodulatory and antiinflammatory activity at high doses. IVIG has notably been used to treat other diseases characterized by elevated interleukin-5 levels and hypereosiniphilia and has been used to treat other severe cutaneous adverse reactions. One hypothesis specific to the effect of IVIG in the treatment of DRESS is that antiviral neutralizing antibodies within IVIG clear the viral infection or reactivation that is thought to contribute to the pathophysiological features of DRESS.