title: Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports.
abstract: BACKGROUND
  Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics.
  
  
  METHODS
  We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients.
  
  
  RESULTS
  Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ.
  
  
  CONCLUSIONS
  It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration.
authors.affiliation: Department of Neuroscience and Behaviour, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP 14048900, Brazil.
authors.forename: Emerson Arcoverde
authors.initials: EA
authors.lastname: Nunes
authors.forename: Tatiana M N
authors.initials: TM
authors.lastname: Rezende
authors.forename: Silvio L
authors.initials: SL
authors.lastname: Morais
authors.forename: José A S
authors.initials: JA
authors.lastname: Crippa
authors.forename: Serdar M
authors.initials: SM
authors.lastname: Dursun
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
keywords: agranulocytosis; clozapine; dengue fever; leucopenia; neutropenia; schizophrenia