Idiosyncratic drug-induced neutropenia & agranulocytosis

Abstract

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.

Diagnosis and Management of Idiopathic Drug-Induced Severe Neutropenia and Agranulocytosis

“…In the USA, reported ranges from 2.4 to 15.4 per million per year [7]. In our experience (observational study in a French hospital), from 1996 to 2017, the annual incidence of symptomatic idiosyncratic agranulocytosis remained stable, with approximately 6 cases per million population [8]. Differences in the observed incidence may be due to different methods/inclusion criteria used in the studies published [1,2].…”

“…Clozapine induces agranulocytosis in almost 1% of patients, particularly in the first three months of treatment, with older patients and females being at a higher risk [11]. In our single centre cohort (n=203), the most frequent causative drugs are: antibiotics (49.3%), especially ß-lactams (n=52) and cotrimoxazole (n=19); antithyroid drugs (16.7%); neuroleptic and anti-epileptic agents (11.8%); antiviral agents (7.9%); and platelet aggregation inhibitors (6.9%), especially ticlopidine (n=10) [8]. Since 1990 and 2000, no case of noramidopyrine-and ticlopidine-induced agranulocytosis was observed, respectively.…”

“…In our cohort study, two thirds of patients received more than two drugs with a mean of three drugs, accounting for the difficulty in definitively identifying the drug responsible for the agranulocytosis. In this cohort, no over "self-medication" was documented [8]. No inappropriate prescribing, as the use of drug that pose more risk than benefit, the misuse of drugs by dose or duration, is also identified.…”

“…It's important to note that without medical intervention, particularly immediate antibiotics administration, natural history of agranulocytosis includes severe and potentially life-threatening infections with often signs of general sepsis and septicaemia (fever, chills, hypotension…). During the evolution, documented pneumonia ( Figure 1) as well as anorectal, skin or oropharyngeal infections and septic shock were the most reported infections [1,2,8]. To date, classical manifestations as necrotic tonsillitis and perinea gangrene or are exceptional.…”

“…It is notable that when antibiotics are administered prophylactically, or at the beginning of this adverse event, both the patient's complaints and the physical findings may be "masked" and fever is often the only clinical sign detected [1,2]. The clinical presentations recorded in our aforementioned cohort study (n=203) mainly included [8]: isolated fever (unknown origin) (26.3%); septicaemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%). While in hospital, 19.2% of the patients worsened clinically and exhibited features of severe sepsis, septic shock, or systemic inflammatory response syndrome (SIRS).…”