Drug-induced Agranulocytosis Research Articles

Erratum to "Severe Drug-Induced Agranulocytosis Successfully Treated with Recombinant Human Granulocyte Colony-Stimulating Factor".

[This corrects the article DOI: 10.1155/2018/8439791.].

Increased risk of antithyroid drug-induced agranulocytosis with amiodarone

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Methimazole-Induced Febrile Neutropenia

Introduction: Antithyroid drugs (ATD) are commonly used for the treatment of thyrotoxicosis, particularly for the treatment of Grave’s disease. Methimazole is the first line ATD. A major fatal adverse effect of ATDs, if unrecognized and not treated on time, is agranulocytosis, which is defined as an absolute neutrophil count of <500/μL. The incidence of ATD-induced agranulocytosis is 0.1%–0.3% (1). In this study, we report on a patient who developed granulocytopenic febrile neutropenia at 3 months after treatment with methimazole (5 mg twice a day per os (BID PO)).Case report: A 51-year-old female patient presented to the emergency department with complaints of fever, fatigue, and productive cough. Her body temperature was 38.5°C; rales were heard on the mid and basal part of the left lung. Drug history revealed methimazole use (10 mg per day over the last 2 months). The WBC count was 1020/μL, and the neutrophil count was 200/μL. The patients’ baseline WBC differential count and immune status were normal. Following inpatient antibiotic treatment and discontinuation of methimazole, the patient became afebrile within 2 days. After 2 weeks of discontinuation of methimazole, we performed CBC and observed the following: WBC, 5180/μL and neutrophil count, 3280/μL.Conclusion: Patients visiting the emergency department with symptoms of a systemic infection and known to use ATDs should be thoroughly evaluated, and the possibility of drug-induced agranulocytosis developing because of the use of these medications should be considered. It is very important for emergency physicians to recognize this rare patient population and act in a timely manner

Diagnosis and management of idiopathic drug-induced and severe neutropenia and agranulocytosis: What should the lung specialist know?

Diagnosis and management of idiopathic drug-induced and severe neutropenia and agranulocytosis: What should the lung specialist know?

Agranulocitoza izazvana lekovima - serija slučajeva

Introduction: Agranulocytosis is a life-threatening disorder characterized by disappearance of granulocytes from peripheral blood or decrease of peripheral neutrophil count below 0.5x109 /l. It frequently occurs as idiosyncratic adverse drug reaction. It occurs especially in association with the use of antithyroid drugs, metamizole, aminopyrine and clozapine. The patients usually present with severe acute infections and sepsis. With modern management of broad-spectrum antibiotics and hematopoietic growth factors (G-CSF) the prognosis has been significantly improved. Methods and results: We present 15 patients with drug-induced agranulocytosis, discuss the criteria for diagnosis, management and prognosis. Median patients age was 36 years (ranging from 25 to 61 years). The male/female ratio was 2/13. Underlying diseases were found in 10/15 (66.6%) patients, consisting of hyperthyreosis in 7 (46.6%) patients, mental disorders in 2 patients (13.3%) and in 1 (6.6%) patient suffering from perianalfistula. Nadir median neutrophil count was 0.3x109 /l, range 0-0.5x109 /l, hemoglobin was between 104 and 128 g/L, anaemia was present in 6 (54.5%) patients, platelet count was between 170 and 230x109 /l. The treatment consisted of broad spectrum antibiotics, hematopoietic growth factor in 10, and antimycotic fluconazole in 3 patients. The outcome was favorable in 14 (93.3%) patients and 1 patient who had thyreotoxic crisis and agranulocytosis died. After 4 months, 1 (6.6%) patient, who had a complete recovery from agranulocytosis, developed an acute myeloid leukemia and died. Conclusions: Drug-induced agranulocytosis is a rare haematological complication, with stable incidence and mortality rate of 5% to 10%. The responsible drug for agranulocytosis must be identified, discontinued and permanently contraindicated.

Synchronous Antithyroid Drug-Induced Agranulocytosis and Fournier Gangrene

ABSTRACT Objective: Antithyroid drugs (ATDs) such as thioimidazoles (e.g., methimazole, also called thiamazole, and carbimazole) and propylthiouracil are commonly used for the treatment of hyperthyroidism. A life-threatening reaction is agranulocytosis with an incidence of 0.1 to 0.5%. There are very few cases in the literature showing that the intake of ATDs finally led to sepsis with accompanying tissue necrosis. Methods: We present an unusual case of severe symptomatic agranulocytosis with sudden development of Fournier gangrene in a patient who was treated with ATDs for hyperthyroidism due to Graves disease. Results: A 69-year-old female was referred to our hospital with fever and a sore throat. For 6 weeks she was treated with methimazole. Laboratory examinations revealed agranulocytosis (total leukocyte count of 0.5 × 109 cells/L, compared to the normal range of 4 to 10 × 109 cells/L, with granulocytes at 0.2% and lymphocytes at 81.3%). The bone marrow aspirate also showed a markedly reduced number ...

Severe Drug-Induced Agranulocytosis Successfully Treated with Recombinant Human Granulocyte Colony-Stimulating Factor

When elderly patients are prescribed many different medications, the risk for developing serious adverse events should be kept in mind. One of these adverse events is agranulocytosis, which, although rare, can be life-threatening if left untreated. The majority of agranulocytosis cases are caused by drugs, including antibiotics. Here, we report a case of severe agranulocytosis in a 96-year-old woman following antibiotic therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the appropriate choice of antibiotics to treat her concomitant infection.

Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis.

We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis. In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. miR-17-92 expression levels in granulocytes of those six patients under the granulocytopenia condition were measured and compared with corresponding granulocyte samples after recovery. Additionally, the expression levels of these miRNAs in patients with type I or type II bone marrow characteristics were analyzed, and the correlation between miR-17-92 and serum free thyroxine level was analyzed. We found that levels of miR-17-92 expression decreased in both serum and pre-agranulocytosis granulocytes from patients with ATD-induced agranulocytosis compared with those in serum and granulocytes from both recovered patients and control patients. However, no difference among patients with either type of bone marrow characteristics was observed, and no correlation between serum miR-17-92 and free thyroxine levels was found. In ATD-induced agranulocytosis, expression of the miR-17-92 cluster is reduced in both serum and granulocytes, though this alteration does not correlate with bone marrow characteristics or thyroid function.

PP-51 Metamizole-induced agranulocytosis in an adolescent treated for chronic headache

Background Metamizole (dipyrone) is used in several European countries to treat pain. Its use has been asso-ciated with agranulocytosis and the incidence of this se-vere adverse drug reaction in adults varies between 1.1 in 1 million patients and 1 out of 1439 prescriptions. In adults the moment at which agranulocytosis is detected is quite variable and ranges from appearing after a sin-gle dose or several months after exposure. So far, these serious adverse drug reactions have been rarely seen in children. Two postauthorisation safety studies in about 1500 children did not report any case of paediatric met-amizole-induced agranulocytosis. However, two cases have been published in children who used metamizole for more than 21 days and 4 weeks, respectively. Case A 14 year old girl was treated with metamizole 2 g/d (26.8 mg/kg/d) for chronic headache which had been prescribed by her general practitioner (GP). Pre-existing atopic dermatitis deteriorated on day 7 of treat-ment, and a sore throat occurred on day 10. On day 12, she consulted her GP who initiated antibiotic treatment with penicillin due to infected and putrid skin lesions. Metamizole was discontinued, but no blood count was ordered. The patient was seen for follow-up two days lat-er since her condition had not improved. A blood count was performed revealing agranulocytosis (neutrophils 0.05 × 10^9/L), and the patient was admitted to hospital. Results Upon admission, treatment with meropenem and teicoplanin was initiated due to septic appearance and shortness of breath. In addition, acyclovir was started due to suspected eczema herpeticum which was later ruled out. Further diagnostic work-up revealed skin le-sions infected with Staphyloccus aureus and multifocal pneumonia. Bronchoalveolar lavage on day 19 to rule out fungal infection was negative for any microorganisms. The patient was treated with granulocyte-colony stimu-lating factor (G-CSF) 30 Million IU for 4 days, during which the neutrophil count recovered. The patient improved clinically and was discharged on day 23 after the initial exposure to metamizole. Conclusion To our knowledge, this is the first report of metamizole-induced agranulocytosis in a paediatric pa-tient who used metamizole for only 12 days. In patients with atopic dermatitis, drug-induced agranulocytosis might show an atypical clinical course by causing skin in-fections as the first presenting symptom. Despite a lower incidence in children than in adults, this serious adverse drug reaction should be kept in mind when prescribing metamizole, and treatment duration should be kept as short (5–7 days) as possible.

Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China

Antithyroid drug (ATD)-induced agranulocytosis is associated with human leukocyte antigen (HLA) and nearby genes in Southeast Asian and European populations. The susceptibility of the Han population from northern China to ATD-induced agranulocytosis has not been reported. We evaluated the associations of genetic variants at the HLA-B and HLA-DRB1 loci and 32 candidate single nucleotide polymorphisms (SNPs) with agranulocytosis in 29 patients with ATD-induced agranulocytosis and in 140 patients with Graves’ disease (GD) as controls. All subjects were of Han descent from northern China. HLA-B*27:05 (P = 1.10 × 10−4), HLA-B*38:02 (P = 2.41 × 10−4) and HLA-DRB1*08:03 (P = 1.57 × 10−3) were susceptibility HLA variants for ATD-induced agranulocytosis. All subjects carrying the HLA-B*27:05 allele had agranulocytosis. The odds ratios (ORs) comparing allele carriers to non-carriers were 66.24 (95% confidence interval (CI): 3.54–1239.66) for HLA-B*27:05, 7.525 (95% CI: 2.294–24.68) for HLA-B*38:02 and 4.316 (95% CI: 1.56–11.93) for HLA-DRB1*08:03. Two SNPs, rs2596487 (OR = 4.196, 95% CI = 2.086–8.441, P = 2.08 × 10−5) and rs2228391 (OR = 3.621, 95% CI = 1.596–8.217, P = 1.2 × 10−3), were independently associated with ATD-induced agranulocytosis. Subjects carrying the ‘A’ allele of rs1811197 or HLA-B*38:02 showed lower minimum granulocyte counts than non-carriers (P = 4.74 × 10−4 and P = 7.39 × 10−4, respectively). Our findings support the association between genetic variations of HLA-B and HLA-DRB1 with ATD-induced agranulocytosis in a Han population from northern China.

Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease.

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole-treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug-induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.

Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center.

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening adverse drug reaction that occurs in patients during the treatment of Graves' disease. We aimed to comprehensively examine data for patients with this rare complication and to improve the clinical safety of ATDs. We retrospectively reviewed the medical records of 64 hospitalized patients diagnosed with ATD-induced agranulocytosis between 2000 and 2015. Agranulocytosis occurred in 52 (81.3%) patients within the first 3months after initiation of ATD therapy. Fever (84.4%) and sore throat (82.8%) were the most common symptoms. Although they experienced symptoms, 30 (46.9%) patients did not seek treatment immediately and delayed their diagnosis of agranulocytosis. The minimum granulocyte count was lower in the patients diagnosed after the appearance of symptoms than in those diagnosed before the appearance of symptoms (0.01 × 109/L (0 × 109/L - 0.06 × 109/L) versus 0.26 × 109/L (0.05 × 109/L - 0.40 × 109/L), P < 0.001). The interval days from the appearance of symptoms to the diagnosis of agranulocytosis were negatively correlated with the minimum granulocyte count (r = -0.348, P = 0.005). In addition, a lower minimum granulocyte count was associated with a longer recovery time (β = -11.899, 95% CI -15.304 to -8.496). Our findings have demonstrated that delayed diagnosis of ATD-induced agranulocytosis is common in our population. Delayed diagnosis is associated with severe agranulocytosis and may prolong the recovery time from agranulocytosis. Monitoring of the white blood cell and granulocyte counts may be an effective way to establish an early diagnosis and prevent progression to severe agranulocytosis.

Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management.

Agranulocytosis is a rare but serious complication of antithyroid drug therapy, and an up-to-date understanding of this topic is important. Both direct toxicity and immune-mediated responses have been described as possible mechanisms. Some major susceptibility loci have recently been identified, which may lead the diagnosis of agranulocytosis into a genomic era. Onset is acute and patients present with symptoms and signs of infection together with high fever. Clinical suspicion is pivotal and should prompt blood sampling. An absolute neutrophil count of <500/μl in the presence of antithyroid drugs establishes the diagnosis. The causative drug should immediately be stopped to prevent further damage. Treatment includes broad-spectrum antibiotics and granulocyte-colony stimulation factor in selected patients. Later, patients will need definitive treatment for hyperthyroidism, usually with radioactive iodine or surgery. The best way to avoid the mortality associated with antithyroid drug-induced agranulocytosis is patient education.

Incidence and risk estimate of drug‐induced agranulocytosis in Hong Kong Chinese. A population‐based case–control study

Drug-induced agranulocytosis is a rare but life-threatening adverse drug reaction. Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with agranulocytosis in Hong Kong Chinese. A population-based case-control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug-induced agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. A total of 155 cases of drug-induced agranulocytosis were identified. Mean age was 51.4 years, and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person-years, and the all-cause mortality of patients with drug-induced agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of agranulocytosis (adjusted OR 416.7, 95% confidence interval (CI) 51.5-3372.9) with an incidence of 9.2 (95%CI 6.9-12.1) per 10 000 users and 3.6 (95%CI 2.7-4.8) per 10 000 user-years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common implicated drug class, and carbimazole had the highest risk of agranulocytosis. Copyright © 2017 John Wiley & Sons, Ltd.

Idiosyncratic drug-induced neutropenia & agranulocytosis.

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.

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

In this paper, we report and discuss the diagnosis and management of severe neutropenia and agranulocytosis (neutrophil count of < 0.5 x 109/L) related to drug intake, thus considered as “idiopathic” in case of unpredictable.

Clinical Development of Histamine H4 Receptor Antagonists.

The discovery of the histamine H4 receptor (H4R) provided a new avenue for the exploration of the physiological role of histamine, as well as providing a new drug target for the development of novel antihistamines. The first step in this process was the identification of selective antagonists to help unravel the pharmacology of the H4R relative to other histamine receptors. The discovery of the selective H4R antagonist JNJ 7777120 was vital for showing a role for the H4R in inflammation and pruritus. While this compound has been very successful as a tool for understanding the function of the receptor, it has drawbacks, including a short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies. Further research let to the discovery of JNJ 39758979, which, similar to JNJ 7777120, was a potent and selective H4R antagonist and showed anti-inflammatory and anti-pruritic activity preclinically. JNJ 39758979 advanced into human clinical studies and showed efficacy in reducing experimental pruritus and in patients with atopic dermatitis. However, development of this compound was terminated due to the occurrence of drug-induced agranulocytosis. This was overcome by developing another H4R antagonist with a different chemical structure, toreforant, that does not appear to have this side effect. Toreforant has been tested in clinical studies in patients with rheumatoid arthritis, asthma, or psoriasis. In conclusions there have been many H4R antagonists reported in the literature, but only a few have been studied in humans underscoring the difficulty in finding ligands with all of the properties necessary for testing in the clinic. Nevertheless, the clinical data to date suggests that H4R antagonists can be beneficial in treating atopic dermatitis and pruritus.

Nonchemotherapy drug-induced agranulocytosis in children detected by a prospective pharmacovigilance program

ABSTRACTObjectives: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. Methods: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA. Results: We detected 662 agranulocytosis in 308 pediatric patients, of which 14 were caused by nonchemotherapy drugs. The incidence rate of DIA for 10,000 pediatric patients was 3.92 (Poisson 95% confidence interval 1.09–8.77); 78.6% of DIA cases occurred in patients younger than 3 years. The final outcome was recovery without sequela in all cases. The pharmacologic group most frequently implicated was antimicrobial drugs (11 drugs), 7 of which were beta-lactams. The drugs most frequently suspected were cefotaxime and vancomycin (3 cases each). We found 3 drugs (cloperastine, codeine, and enoxaparin) not previously described to induce DIA. Automatic linear modeling (n = 56, R2 = 45.2%) showed a significant inverse association with platelets (R2 = 17.5%), hemoglobin, and alanine transaminase, and a direct association with red cell distribution (R2 = 16.2%). A generalized linear model (Type III, n = 1188; DIA, n = 86; likelihood ratio chi-squared = 156.16) retained eosinophils (p <.001), platelets (p <.001), total serum proteins (p <.001), and hemoglobin (p =.039). Conclusions: We found a higher incidence of DIA in children than previously described. Our findings also suggest an immune-mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure.

The Effects of GCSF on the Recovery Time and Duration of Hospitalization in Patients with Anti-thyroid Drug-Induced Agranulocytosis in a Tertiary Hospital

Objectives. This study aims to determine if there is a significant difference in the recovery time and duration of hospital stay of patients with anti-thyroid drug-(ATD) induced agranulocytosis with and without granulocyte colony-stimulating factor (GCSF) therapy. It also aims to describe the clinical characteristics of patients who had anti-thyroid drug-induced agranulocytosis. Methodology. This is a retrospective study of hyperthyroid patients on anti-thyroid drugs (ATD) who had an absolute neutrophil count (ANC) of less than 500/μL. Their charts were reviewed for collection of data on age, gender, body mass index (BMI), type and duration of ATD and use of antibiotic and steroid. Recovery time and length of hospital stay were compared between those who received and did not receive GCSF. Results. TWith similar clinical features between the GCSF and non-GCSF groups, the recovery time from agranulocytosis and duration of hospitalization were significantly shorter in the GCSF group, despite lower ANC. Conclusion. GCSF significantly decreased recovery time (4 versus 7 days, p=0.005) and duration of hospital stay (5 versus 7 days, p=0.009) of hyperthyroid patients with anti-thyroid drug-induced agranulocytosis compared to patients not given GCSF.

Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis in Elderly Patients (≥75years): A Monocentric Cohort Study of 61 Cases.

BackgroundLittle 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.ObjectiveWe herein describe the clinical picture and outcome of patients aged ≥75 years with established idiosyncratic drug-induced agranulocytosis.Patients and MethodsData 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.ResultsThe 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).ConclusionsOur 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 %).