Angioedema in a patient with COVID-19 who received depot olanzapine pamoate: Diagnostic dilemma posed.

Sir,

Angioedema is a rare life-threatening adverse effect of antipsychotics. It has been reported with oral antipsychotics such as olanzapine, clozapine and risperidone primarily.[1] Reports of long-acting injectable (LAI) antipsychotic-induced angioedema are sparse. We hereby report a case of angioedema with olanzapine pamoate LAI (OLAI) in a boy who also concomitantly contracted COVID-19 infection while discussing the diagnostic dilemma posed by their co-occurrence.

A 16-year-old boy presented to the casualty with acute-onset edema in the periorbital and perioral region [Figure 1] that progressed over 2–3 days to an extent that he could barely eat and talk. This was also accompanied by fever and cough for the same duration. On presentation, he was tested for SARS-CoV-2, which was positive. He was admitted and diagnosed as angioedema along with COVID-19. His routine laboratory parameters along with serum albumin; C3 and C4; immunoglobulins E (IgE), M, and G; and creatinine phosphokinase were normal, and he was conservatively managed with corticosteroids, antihistaminics, and antipyretics. Because angioedema is not a common manifestation of COVID-19, the treating team tried to clarify the cause, and it surfaced that he was administered OLAI (300 mg) 8 days before by a private psychiatrist because of affective symptoms. A psychiatry call was given and on evaluation, he was found to be suffering from a manic episode for 2 weeks before being administered the depot medication. On resolution of edema and on attaining a discharge status for his COVID-19 condition, he was treated with sodium valproate and haloperidol, and he was discharged on improvement of manic symptoms.

Figure 1

Edema in the periorbital and perioral region

Angioedema in this boy developed 8 days after OLAI administration at a time when he also tested COVID-19 positive. This posed a diagnostic challenge as to whether it was a manifestation of COVID-19 or an adverse reaction to OLAI. Angioedema has been reported in the setting of COVID-19 in a female who also developed urticaria that resolved on treatment.[2] Nevertheless, there also remained a reason to suspect OLAI to be the causative.

OLAI was administered 8 days prior to the onset of angioedema in our case. Considering the fact that plasma olanzapine concentration peaks after a week of OLAI administration,[3] it can be postulated that the occurrence of side effects with its administration could also match with this peak plasma level. This was also strengthened by the fact that “edema-like reactions” have been reported with OLAI.[3] Both these factors hint that this angioedema could also possibly have occurred due to the depot antipsychotic. Until today, among LAI, only risperidone and paliperidone have been reported to cause angioedema.[45] The mechanism is unclear but can be postulated to be an antipsychotic-induced IgE-mediated type-1 hypersensitivity reaction causing increased vascular permeability.[5] In our case, it was difficult to distinguish whether the angioedema was due to COVID-19 or due to OLAI, but we could hypothesize that as both employs similar pathogenetic mechanisms in its causation, their effect could have summated in our case, leading to the life-threatening edema.

Irrespective of the causative link, it calls for remaining vigilant when administering any LAI antipsychotic (OLAI in our case), more so when encountering any suspected case of COVID-19 during the current pandemic.

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Conflicts of interest

There are no conflicts of interest.