title: Idiosyncratic drug-induced neutropenia & agranulocytosis.
abstract: Few data is currently available on neutropenia and agranulocytosis related to drug intake. We report here data on 203 patients with established idiosyncratic drug-induced agranulocytosis, followed up in a referral centre within a university hospital.
  
  
  
  Data from 203 patients with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis in the Strasbourg University Hospital (Strasbourg, France) RESULTS: : The mean age was 61.6 years old (range: 18-95), the gender ratio (F/M) was 1.3. Several comorbidities were present in 63.5%. The most frequent causative drugs were: antibiotics (49.3%), especially ß-lactams and cotrimoxazole; antithyroid drugs (16.7%); neuroleptic and anti-epileptic agents (11.8%); antiviral agents (7.9%); and platelet aggregation inhibitors as ticlopidine and acid acetylsalicylic (6.9%). The main primary clinical manifestations during hospitalization included: isolated fever (26.3%); septicaemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%). The mean neutrophil count at nadir was 0.148 x 109/L (range: 0-0.48). All febrile patients were treated with broad-spectrum antibiotics and 107 (52.7%) with hematopoietic growth factors. The mean duration of haematological recovery (neutrophil count ≥1.5 x 109/L) was 7.8 (range: 2-20). This mean duration was reduced to 2.1 days (range: 2-16) (p = 0.057) with hematopoietic growth factors. Outcome was favourable in 91.6% of patients; seventeen died. Thirty-seven patients (18.2%) required intensive care.
  
  
  
  The present study demonstrated that idiosyncratic drug-induced agranulocytosis is a relative rare events; that antibiotics, antithyroid, neuroleptic and anti-epileptic agents, and platelet aggregation inhibitors are the main incriminated drug classes; that agranulocytosis typically serious, with at least 50% exhibiting severe sepsis and a mortality rate <10%; and that modern management of such disorder may reduce the infection-related mortality.
authors.affiliation: Departments of Internal medicine.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Andrès
authors.affiliation: Departments of Internal medicine.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mourot-Cottet
authors.affiliation: Onco-hematology.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maloisel
authors.affiliation: , Statistics.
authors.forename: François
authors.initials: F
authors.lastname: Séverac
authors.affiliation: Departments of Internal medicine.
authors.forename: Olivier
authors.initials: O
authors.lastname: Keller
authors.affiliation: , Geriatrics4.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogel
authors.affiliation: , Geriatrics4.
authors.forename: Martine
authors.initials: M
authors.lastname: Tebacher
authors.affiliation: Departments of Internal medicine.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Weber
authors.affiliation: , Geriatrics4.
authors.forename: Georges
authors.initials: G
authors.lastname: Kaltenbach
authors.affiliation: of the Strasbourg University Hospitals; France, and the Regional Pharmacovigilance Centre of Alsace.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Departments of Internal medicine.
authors.forename: Bernard
authors.initials: B
authors.lastname: Goichot
authors.affiliation: of the Strasbourg University Hospitals; France, and the Regional Pharmacovigilance Centre of Alsace.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Departments of Internal medicine.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Korganow
authors.affiliation: Onco-hematology.
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
keywords: Agranulocytosis; Antibiotic; Drug; Hematopoietic growh factor; Infection; Neutropenia