title: Treatment of DIHS/DRESS syndrome with combined N-acetylcysteine, prednisone and valganciclovir--a hypothesis.
abstract: BACKGROUND
  Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a rare and severe adverse drug reaction with an associated mortality of 10-20%. Clinical worsening despite discontinuation of the culprit drug is considered a characteristic feature of DIHS/DRESS. Besides the early recognition of the syndrome and discontinuation of its causative drug, the mainstay of treatment is systemic corticosteroids. Nevertheless, treatment of severe DIHS/DRESS is not well defined, as corticosteroids may sometimes not be effective, and decreasing the dose may be associated with flaring of the disease.
  
  
  METHODS
  A 38-year-old woman with high fever, malaise, abdominal pain, rash, and elevated liver enzymes received immediate high-dose N-acetylcysteine, because acetaminophen hepatotoxicity was suspected. N-acetylcysteine administration was associated with a significant clinical improvement. However, within the next week DIHS/DRESS syndrome was diagnosed, which explained all the symptoms, and which was subsequently treated with prednisone and valganciclovir.
  
  
  CONCLUSIONS
  New options necessary to improve treatment of severe DIHD/DRESS have to consider its sequential pathogenetic mechanisms. N-acetylcysteine might neutralize the drug-derived reactive metabolites, which are responsible for protein adduct formation and specific T cell stimulation, and replete the glutathione stores that counterbalance oxidative stress. Prednisone might inhibit lymphoproliferation and valganciclovir might prevent complications related to HHV-6 reactivation. We therefore propose the unprecedented combination of N-acetylcysteine, prednisone and valganciclovir as a treatment option for DIHS/DRESS.
authors: Division of Infectious Diseases, Ospedale Generale, Bolzano, Italy. molosw@hotmail.com
authors: Oswald
authors: O
authors: Moling
authors: Lukas
authors: L
authors: Tappeiner
authors: Andrea
authors: A
authors: Piccin
authors: Elisabetta
authors: E
authors: Pagani
authors: Patrizia
authors: P
authors: Rossi
authors: Giovanni
authors: G
authors: Rimenti
authors: Claudio
authors: C
authors: Vedovelli
authors: Peter
authors: P
authors: Mian
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D004342:Drug Hypersensitivity / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004802:Eosinophilia / Q000150:complications / Q000188:drug therapy*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D011241:Prednisone / Q000627:therapeutic use*; D000077562:Valganciclovir
chemical_list: D000077562:Valganciclovir; D015774:Ganciclovir; D011241:Prednisone; D000111:Acetylcysteine