Abstract
Angioedema is an abrupt transient swelling of the deep skin layers and/or mucous membranes due to vessel dilation and subsequent plasma leakage into the interstitium. It is broadly classified into two subtypes: nonhistaminergic and histaminergic angioedema. Nonhistaminergic angioedema is bradykinin-mediated and is commonly seen as a result of angiotensin-converting-enzyme-inhibitor use, and more rarely as a result of genetic disorders. Histaminergic angioedema, the most prevalent form, occurs secondary to mast-cell degranulation through IgE mediation or direct activation of mast cells; it is frequently accompanied by urticaria (Cicardi et al. 2014).
Although rare, angioedema and urticaria have been reported as a side effect of multiple antipsychotic medications, including risperidone, clozapine, and ziprasidone, but to our knowledge has not been described in case reports as a result of aripiprazole administration (Soumya et al. 2010). Aripiprazole, a D2, 5HT1A partial agonist, is utilized in pediatric populations for the treatment of acute mania, psychomotor agitation, and Tourette's syndrome. In this study, we report a pediatric patient who developed apparent angioedema of the tongue, lips, and face after treatment with oral aripiprazole, which resolved after administration of intramuscular (IM) diphenhydramine.
A 9-year-old African American boy with diagnoses of attention-deficit/hyperactivity disorder, intellectual disability (mild), and oppositional defiant disorder was hospitalized due to impulsivity and physical aggression. He was continued on home medications of clonidine 0.1 mg qHS and methylphenidate OROS 36 mg qAM. Aripiprazole 2.5 mg was added to reduce aggression. The patient has a prior trial of haloperidol (the patient's mother was unable to recall the dosage used), which was discontinued secondary to “neck pain.”
After his third dose of aripiprazole the patient reported anxiety, nausea, and 8/10 neck/throat pain. His tongue was visibly swollen, but he did not display any visible respiratory distress, increased motor tone, or other dyskinesias. There were no reports of him having eaten any unusual foods or given any new medications. He was administered hydroxyzine 12.5 mg and acetaminophen 250 mg. Shortly afterward, the patient's tongue, lips, and right side of his face became swollen and red. Diphenhydramine 50 mg IM was administered. Vitals at this time were temperature 98.0°F, blood pressure 126/99 mmHg, SPO2 100%, pulse 118 beats/min, and respiratory rate 18 breaths/min. He was re-examined 30 minutes later and all symptoms except for tremulousness were resolved and vitals were stable.
Histaminergic angioedema, although rare, is a potentially life-threatening side effect of many antipsychotics, including aripiprazole. Although individual episodes of angioedema progress rapidly, the period between onset of drug administration and first-episode of angioedema varies greatly. Some case-reports document first-episode angioedema in individuals who have been maintained on a steady dose of a single antipsychotic for years, whereas others report onset within 2–3 days from first dose, as was the case with our patient (Gürbüz et al. 2020; Raja and Azzoni 2001). In general, it appears that patients developing angioedema can safely be trialed on a different antipsychotic, but a select few individuals seem to exhibit broad cross-reactivity across both typical and atypical antipsychotics. Clinicians continuing or starting patients on an antipsychotic should be aware of this complication, as well as the recommended treatment with antihistamines, corticosteroids, and epinephrine in particularly severe cases.
Footnotes
Disclosures
No competing financial interests exist.