ABSTRACT
AIM: We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors. METHODS: All peripheral eosinophilia >700 × 106 cells l-1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed. RESULTS: The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected. CONCLUSIONS: Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.
Subject(s)
Drug Hypersensitivity Syndrome/epidemiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Eosinophilia/chemically induced , Pharmacovigilance , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Drug Eruptions/pathology , Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/physiopathology , Eosinophilia/epidemiology , Eosinophilia/physiopathology , Female , Hospitalization , Humans , Incidence , Infant , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Tertiary Care Centers , Young AdultABSTRACT
OBJECTIVES: 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.
Subject(s)
Agranulocytosis , Cefotaxime/adverse effects , Codeine/adverse effects , Enoxaparin/adverse effects , Piperidines/adverse effects , Vancomycin/adverse effects , Age Factors , Agranulocytosis/chemically induced , Agranulocytosis/diagnosis , Agranulocytosis/epidemiology , Agranulocytosis/therapy , Cefotaxime/administration & dosage , Child , Child, Preschool , Codeine/administration & dosage , Enoxaparin/administration & dosage , Female , Humans , Infant , Infant, Newborn , Male , Piperidines/administration & dosage , Prospective Studies , Vancomycin/administration & dosageABSTRACT
We conducted a prospective evaluation of non-chemotherapy-induced agranulocytosis (NIA) in a tertiary hospital in Spain. Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital, we detected agranulocytosis cases over a period of 42 consecutive months. This report estimates incidence, drug causality, clinical features and outcomes of NIA cases and assesses laboratory differences with respect to non-NIA. We detected 1349 cases of agranulocytosis in 538 adult patients; of these, 43 cases in 40 patients were caused by non-chemotherapy drugs. The incidence rate for 10,000 patients during the study period was 2.75 [Poisson confidence interval (CI)-95%: 0.62-7.22]. The mean (S.D.) age was 48 (21) years. All cases were categorized as serious, because they required hospitalization (28 cases) or prolongation of hospitalization (15 cases). The outcome was recovery without sequela (39 cases), recovery with sequela (one case of toe amputation) or death (three cases, 7%). The most frequent cause of NIA was antimicrobial drugs (19 cases). The highest incidence rate per 10,000 defined daily doses was for cefepime (83.85; Poisson-CI 95%: 67-102.89). Automatic linear modelling (n = 75, R(2) = 77.9%) showed a significant inverse association with platelets, alkaline phosphatase, C-reactive protein, fibrinogen, lactate dehydrogenase; and direct association with mean corpuscular haemoglobin, and haematocrit. A generalized linear model retained platelets, total serum proteins, creatinine and haemoglobin. The findings suggest an immune-mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure. There might be additional contributing factors, such as nutritional deficiencies or chronic diseases, to develop NIA after exposure to a potentially causative drug.