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Ethosuximide induced agranulocytosis
Tadashi Imai1, Hitoshi Okada, Masanori Nanba
1Department of Pediatrics, Kagawa Medical University, Ikenobe 1750-1, Miki, Kitagun, Kagawa 761-0793, Japan. taboimai@kms.ac.jp
Insights
Agranulocytosis, a rare but serious side effect of ethosuximide, can be fatal if diagnosis is delayed. Early detection and intervention, like using granulocyte colony-stimulating factor, are crucial for survival in children.
Area of Science:
- Pediatrics
- Hematology
- Pharmacology
Background:
- Agranulocytosis is a rare but life-threatening adverse effect of certain medications.
- Ethosuximide is an antiepileptic drug primarily used to treat absence seizures.
- Prompt diagnosis and management of drug-induced agranulocytosis are critical to prevent fatal outcomes.
Observation:
- A 16-month-old infant with Down syndrome developed fever and severe pneumonia 16 days after starting ethosuximide.
- Initial blood tests revealed a significantly decreased leukocyte count (1700/microl) with an absence of granulocytes.
- Bone marrow aspiration confirmed a lack of granulocyte production, indicating severe agranulocytosis.
Findings:
- The patient required mechanical ventilation for pneumonia and developed disseminated intravascular coagulation.
- Discontinuation of ethosuximide and administration of granulocyte colony-stimulating factor led to an increase in neutrophilic leukocytes.
- A drug-induced lymphocyte stimulation test confirmed ethosuximide as the causative agent.
Implications:
- This case highlights the potential for ethosuximide to cause severe agranulocytosis in children, even those with underlying conditions like Down syndrome.
- The immunologic mechanism is suspected, emphasizing the need for vigilance regarding sudden onset of symptoms 1-2 weeks after drug initiation.
- Early diagnosis, supported by tests like the drug-induced lymphocyte stimulation test, and prompt treatment are vital for patient survival.
Abstract:
Agranulocytosis caused by ethosuximide is extremely rare in children. Drug-induced agranulocytosis is an unexpected side effect of a drug, and delay in diagnosis of agranulocytosis can result in a fatal outcome. We experienced a case of a 16-month-old male infant with Down syndrome in whom fever appeared 16 days after the start of administration of ethosuximide and then severe pneumonia developed. Results of a blood test on admission showed a decreased leukocyte count of 1700/microl, and a hemogram showed that there were no granulocytes. The erythrocyte and thrombocyte counts were within normal ranges. The results of a bone marrow aspiration test showed that there was no production of any types of granulocytes. The patient required mechanical ventilation due to deterioration in his pneumonia and complication with disseminated intravascular coagulation, but the neutrophilic leukocytes began to increase from the 8th day after discontinuation of ethosuximide administration and start of treatment with granulocyte colony-stimulating factor, and the patient survived. The mechanism of onset in this case is thought to have been immunologic. Careful attention should be given to this type of agranulocytosis because of its sudden onset at 1-2 weeks after the start of administration of the causal drug. A drug-induced lymphocyte stimulation test was useful for diagnosis in this case, showing a positive reaction only for ethosuximide.
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