title: Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis in Elderly Patients (≥75 years): A Monocentric Cohort Study of 61 Cases.
abstract: BACKGROUND
  Little data is currently available in the literature on neutropenia and agranulocytosis in the elderly, and, to our knowledge, idiosyncratic drug-induced agranulocytosis is particularly poorly covered, or not at all.
  
  
  OBJECTIVE
  We herein describe the clinical picture and outcome of patients aged ≥75 years with established idiosyncratic drug-induced agranulocytosis.
  
  
  METHODS
  Data from 61 patients over 75 years old with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis (n = 203) in the Strasbourg University Hospitals (Strasbourg, France), a referral center.
  
  
  RESULTS
  The mean age was 84.9 years (range 75-95), the gender ratio (F/M) was 2.4. Underlying diseases were present in 74 %. The most frequent causative drugs were antibiotics (43.8 %), antithyroid drugs (15.8 %), neuroleptic and anti-epileptic agents (12.3 %), and antiaggregant platelet agents (10.5 %). The primary clinical features during hospitalization included isolated fever (27.6 %), septicemia or septic shock (24.1 %), and pneumonia (20.7 %). The mean neutrophil count at nadir was 0.15 × 109/L (range 0-0.4). All febrile patients were treated with broad-spectrum antibiotics and 36 with hematopoietic growth factors. Outcome was favorable in 85.3 % of patients; nine patients died. Two elderly patients (3.3 %) died of uncontrolled septic shock relating to the depth of the neutropenia. Comparison of mortality between <75- and ≥75-year-old patients revealed a statistical difference: 4.2 % versus 14.8 % (p = 0.023).
  
  
  CONCLUSIONS
  Our study demonstrates that 30 % of idiosyncratic drug-induced agranulocytosis concerned elderly patients. Antibiotic, antithyroid, neuroleptic, anti-epileptic, and antiaggregant platelet agents are the primary causative drug classes. Idiosyncratic drug-induced agranulocytosis is typically serious in this frail population of elderly patients, with at least 50 % suffering from severe sepsis and with a mortality rate of approximately 15 %. Modern management of agranulocytosis may reduce the infection-related mortality (3.3 %).
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mourot-Cottet
authors.affiliation: Department of Onco-Hematology, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maloisel
authors.affiliation: Department of Statistics, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Séverac
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Keller
authors.affiliation: Department of Geriatrics, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogel
authors.affiliation: Regional Pharmacovigilance Center of Alsace, Strasbourg, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Tebacher
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Weber
authors.affiliation: Department of Geriatrics, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Kaltenbach
authors.affiliation: Department of Rheumatology, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Goichot
authors.affiliation: Department of Rheumatology, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Korganow
authors.affiliation: Department of Onco-Hematology, Strasbourg University Hospitals, Strasbourg, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.affiliation: Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France. emmanuel.andres@chru-strasbourg.fr.|Service de Médecine Interne, Diabète et Maladies Métaboliques, Clinique Médicale B, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, 67 091, Strasbourg Cedex, France. emmanuel.andres@chru-strasbourg.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Andrès