Clozapine-induced severe eosinophilia: report of a case with good outcome

Abstract

Introduction: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. Methods: Case report and literature review. results: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm 3 . Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. Conclusion: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.

Clozapine-induced eosinophilia: A case report

“…Marcelino and de Rosalmeida Dantas described a case where clozapine was discontinued at the value of 1500/mm 3 eosinophils but restarted after normalization. 10 The patient did not develop eosinophilia again. Patients who have discontinued clozapine as a result of confirmed agranulocytosis tend to experience a rapid and severe recurrence of neutropenia on clozapine rechallenge, which does not appear to be the case for many patients who develop eosinophilia when treated with clozapine.…”

“…Most of the literature consists of case reports in which the authors report that eosinophilia, whenever it develops, is usually seen during the initial phase of clozapine treatment, usually within the first 3-6 weeks of therapy. [9][10][11] In these studies, it is also observed that, in most cases, clozapine-induced eosinophilia resolves spontaneously without the need to modify the drug dose or discontinue it. In none of the cases was clozapine discontinuation required, and in most cases the eosinophilia resolved spontaneously 3-4 weeks after initiation.…”

“…The pathophysiology of clozapine-induced eosinophilia is not yet well understood, but proposed mechanisms include a type I hypersensitivity reaction, 19 , 33 and a direct toxic effect on the bone marrow. 10 , 33 It is also possible that both mechanisms might co-exist or that other different mechanisms might also be involved. Clozapine-induced eosinophilia may be transient or may present with inflammation and end-organ damage such as myocarditis.…”

“…This case adds to the existing literature that clozapine-induced eosinophilia is mostly a benign and transient reaction that develops during the first weeks of treatment. 9 – 11 There is limited information on the management of clozapine-induced eosinophilia, but close monitoring with eosinophil count, inflammatory markers, liver function tests (LFT), and echocardiography (ECG) changes should be considered, and discontinuation of clozapine treatment should be considered if end-organ damage is suspected.…”