State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies
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...
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MDPI AG
2019-09-01
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Online Access: | https://www.mdpi.com/2077-0383/8/9/1351 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emmanuel Andrès Noel Lorenzo Villalba Abrar-Ahmad Zulfiqar Khalid Serraj Rachel Mourot-Cottet Jacques-Eric Gottenberg |
spellingShingle |
Emmanuel Andrès Noel Lorenzo Villalba Abrar-Ahmad Zulfiqar Khalid Serraj Rachel Mourot-Cottet Jacques-Eric Gottenberg State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies Journal of Clinical Medicine drug idiosyncratic neutropenia agranulocytosis infections antithyroid medications ticlopidine clozapine sulfasalazine antibiotics as trimethoprim-sulfamethoxazole (cotrimoxazole), and deferiprone biotherapy autoimmune disease auto-inflammatory disorder systemic vasculitis orphan disease anti-TNF-alpha agent anti-CD20 agent IL1-inhibitor IL6 inhibitor B-cell activating factor (BAFF) inhibitor |
author_facet |
Emmanuel Andrès Noel Lorenzo Villalba Abrar-Ahmad Zulfiqar Khalid Serraj Rachel Mourot-Cottet Jacques-Eric Gottenberg |
author_sort |
Emmanuel Andrès |
title |
State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies |
title_short |
State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies |
title_full |
State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies |
title_fullStr |
State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies |
title_full_unstemmed |
State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies |
title_sort |
state of art of idiosyncratic drug-induced neutropenia or agranulocytosis, with a focus on biotherapies |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-09-01 |
description |
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: “drug-induced neutropenia”, “drug-induced agranulocytosis”, and “idiosyncratic agranulocytosis”. 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) ≤ 0.5 × 109/L and ≤ 0.1 × 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 1−2 neutropenia (absolute blood NC between 1.5 and 0.5 × 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 3−4 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 ‘susceptible’ patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 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. |
topic |
drug idiosyncratic neutropenia agranulocytosis infections antithyroid medications ticlopidine clozapine sulfasalazine antibiotics as trimethoprim-sulfamethoxazole (cotrimoxazole), and deferiprone biotherapy autoimmune disease auto-inflammatory disorder systemic vasculitis orphan disease anti-TNF-alpha agent anti-CD20 agent IL1-inhibitor IL6 inhibitor B-cell activating factor (BAFF) inhibitor |
url |
https://www.mdpi.com/2077-0383/8/9/1351 |
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doaj-7381138adb63420e8690c8d1f72d25202020-11-25T01:20:09ZengMDPI AGJournal of Clinical Medicine2077-03832019-09-0189135110.3390/jcm8091351jcm8091351State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on BiotherapiesEmmanuel Andrès0Noel Lorenzo Villalba1Abrar-Ahmad Zulfiqar2Khalid Serraj3Rachel Mourot-Cottet4Jacques-Eric Gottenberg5Department of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, FranceDepartment of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, FranceDepartment of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, FranceDepartments of Internal Medicine, University Hospital of Oujda, 59000 Oujda, MoroccoDepartment of Internal Medicine, Medical Clinic B, University Hospital of Strasbourg, 67084 Strasbourg, FranceDepartment of Rheumatology, University Hospital of Strasbourg, 67084 Strasbourg, FranceIntroduction: 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: “drug-induced neutropenia”, “drug-induced agranulocytosis”, and “idiosyncratic agranulocytosis”. 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) ≤ 0.5 × 109/L and ≤ 0.1 × 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 1−2 neutropenia (absolute blood NC between 1.5 and 0.5 × 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 3−4 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 ‘susceptible’ patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 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.https://www.mdpi.com/2077-0383/8/9/1351drugidiosyncraticneutropeniaagranulocytosisinfectionsantithyroid medicationsticlopidineclozapinesulfasalazineantibiotics as trimethoprim-sulfamethoxazole (cotrimoxazole), and deferipronebiotherapyautoimmune diseaseauto-inflammatory disordersystemic vasculitisorphan diseaseanti-TNF-alpha agentanti-CD20 agentIL1-inhibitorIL6 inhibitorB-cell activating factor (BAFF) inhibitor |