Abstract
Clozapine is an atypical antipsychotic which is generally used as a second line antipsychotic drug in clinical practice due to its side effects. It is known that Clozapine may induce hypersensitivity reaction, angioedema at the beginning of the treatment, late onset angioedema related to clozapine treatment is very rare in the literature. In this case report, we present a 19 years old man who was admitted to psychiatry with clozapine induced periorbital edema. He was receiving clozapine 200 mg per day for last two years when he applied to psychiatry. After reducing daily dose of clozapine to 150 mg, his periorbital edema regressed. It should be known that clozapine induced angioedema may develop not only at the beginning of the treatment but also during the treatment and may regress with dose reduction.
Key words: Clozapine, late-onset angioedema, periorbital edema
INTRODUCTION
There are few case reports in the literature regarding clozapine-related periorbital edema. The majority of that cases have reported angioedema during the initial phase of treatment or within the first 6 weeks of clozapine treatment,[1,2,3] except for only one case reported in which a angioedema was noted after 5 years of starting treatment.[4]
These reports have not reported any specific blood parameter associated with angioedema.[1,2,3] In all cases, it was reported that angioedema decreased with clozapine discontinuation. In this case report, we present a 19-year-old male who developed bilateral periorbital edema during 2nd year of clozapine treatment.
CASE REPORT
A 19-year-old male was diagnosed with schizophrenia at the age of 14 two years ago. He was referred to the child psychiatry inpatient unit, where he was started on 200 mg/day clozapine. With clozapine, his psychotic symptoms reduced and he remained in remission for the past 1 year. After being continued on 200 mg/day of clozapine for 2 years, he was admitted to infectious disease ward with unexplained bilateral periorbital edema. He did not have any history or evidence of fever, urticaria, and pruritus. Detailed blood tests were performed. The results of blood count (white blood cell: 77x103 /uL, hemoglobin: 12.9 g/dL, platelet: 408x103 /uL, aspartate transaminase: 21 U/L, alanine transaminase: 27 U/L, creatinine: 0.63, and C-reactive protein: 43.7) were within the range. On eye examination, anterior and posterior segment examination of the eyes was normal and eye movements were free of motion in every side, and there is no abnormal pupil response. The family history regarding allergic reactions was unremarkable. He received antibiotic and steroid treatment. However, he did not respond to antibiotic and steroid treatment and he was referred to the psychiatry department considering his periorbital edema could be related to antipsychotics that he took.
After psychiatric evaluation, the daily dose of clozapine was reduced to 150 mg. Four days after changing his clozapine dose, angioedema subsided completely.
DISCUSSION
Angioedema is a clinical syndrome which is characterized by swelling of the skin and submucosal tissue due to increased secretion of histamine, serotonin, and quinine and classified as hereditary and acquired angioedema.[5] The most common sites of predilection are lip and eyes (periorbital edema). Angioedema is usually treated with antihistamine and steroids. However, in this case, angioedema did not respond steroid and antihistamine treatment. Angioedema without urticaria and not responding to antihistamines can be related to bradykinin-mediated angioedema such as angiotensin-converting enzyme inhibitor-induced angioedema.[6] In the literature, although there are case series regarding clozapine and other antipsychotics-induced angioedema,[7] late-onset angioedema associated with clozapine treatment was shown in only one case and the mechanism behind the late-onset angioedema was not clear.[4]
The mechanism of clozapine-induced reactions might be justified with receptor mechanisms.[3] However, allergic reactions associated with clozapine reported in the literature mostly developed within 4 days to 6 weeks.[2,3,4] However, in our case, periorbital edema occurred 2 years after the treatment and it was not accompanied with any symptoms such as urticaria and it regressed with dose reduction.
Although hypersensitivity reactions with antipsychotic agents have been reported before,[7] the late onset of our case is noteworthy for etiological reasons. All those symptoms, laboratory findings, and evaluation of our case and the case mentioned above have shown that the mechanisms behind late-onset angioedema related to clozapine still need to be investigated more.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
The authors would like to thank the department of psychiatry and the patient for giving consent form to publish this case report.
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