{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:01:04Z","timestamp":1782950464200,"version":"3.54.5"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases. Materials and methods: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: \u201cdrug-induced neutropenia\u201d, \u201cdrug-induced agranulocytosis\u201d, and \u201cidiosyncratic agranulocytosis\u201d. We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor. Results: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) \u2264 0.5 \u00d7 109\/L and \u2264 0.1 \u00d7 109\/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1\u20132 neutropenia (absolute blood NC between 1.5 and 0.5 \u00d7 109\/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3\u20134 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying \u2018susceptible\u2019 patients. Older age (&gt;65 years), septicemia or shock, renal failure, and a neutrophil count \u22640.1 \u00d7 109\/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent\/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF). Conclusion: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies.<\/jats:p>","DOI":"10.3390\/jcm8091351","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T03:16:12Z","timestamp":1567394172000},"page":"1351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7914-7616","authenticated-orcid":false,"given":"Emmanuel","family":"Andr\u00e8s","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Lorenzo Villalba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar-Ahmad","family":"Zulfiqar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Serraj","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, University Hospital of Oujda, 59000 Oujda, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Mourot-Cottet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques-Eric","family":"Gottenberg","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital of Strasbourg, 67084 Strasbourg, France"},{"name":"Referral Center of Immune Cytopenias, University Hospital of Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1586\/ehm.11.12","article-title":"Clinical presentation and management of drug-induced agranulocytosis","volume":"4","author":"Zimmer","year":"2011","journal-title":"Expert Rev. 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