Cetirizine-induced psychosis in a young adult with erythema multiforme

Background

Cetirizine is a second-generation H1-inverse agonist selective for peripheral H1 receptors, primarily used in the treatment of allergic rhinitis and chronic idiopathic urticaria.1 2 Off-label, it is commonly used for a number of pruritic dermatological conditions as part of treatment and symptom management. Unlike first-generation antihistamines, second-generations have minimal anticholinergic activity; however, psychomotor impairment and central nervous system (CNS) effects have been described, including somnolence and paradoxical excitability.1–3 There have been multiple cases of first-generation antihistamine-induced psychosis with promethazine and other first-generation antihistamines in young and healthy populations.4–6

Case presentation

A man in his late 20s with no psychiatric history was brought by his mother to the emergency department in September 2020 due to two discrete episodes of unusual aggressive behaviour, agitation, paranoia, short-term memory loss and auditory and visual hallucinations, which began in the context of new cetirizine use for a pruritic cutaneous eruption. He presented to his family physician 2 weeks after onset of rash and was prescribed 20 mg cetirizine one time per day. He took cetirizine for 2 days before the onset of visual and auditory hallucinations of family members and paranoid delusions about an unidentified ‘family’ in his backyard targeting him. No other routine medications were taken. These symptoms resolved with cetirizine cessation; however, given the persistence of his rash and pruritus, he took a third dose on day 5, resulting in acute recurrence of his psychotic symptoms and aggressive behaviour. He was admitted to psychiatry for diagnostic clarification and stabilisation. He had a past medical history of treated primary syphilis and recurrent herpes simplex labialis. On review of systems by collateral and retrospectively since discharge, he had suffered from self-limited coryza, pharyngitis and subjective fever (chills, rigours), as well as a herpetic lesion in the week prior to the onset of rash, but no other systemic symptoms. He also retrospectively reported involvment in a motor vehicle collison (MVC) 4 months prior that led to physical injuries (brachial plexopathy) and has been experiencing depressive symptoms ever since.

On mental status examination, the patient appeared disorganised in thought process, responding non-linearly to questions and endorsing paranoia and persecutory delusions about his family members. He reported visual hallucinations of an unidentified ‘family’ targeting him at home. He appeared to be responding to internal stimuli and was observed to be running out of his room on multiple occasions, as if trying to avoid a presence in his room.

Dermatological examination revealed resolving red-purple papules and nodules distributed on the anterior and posterior trunk, as well as the proximal extremities, with greater upper than lower limb involvement. Many of these were flattening and non-tender on palpation. The palms and soles were spared. Mucosal erosions were noted on the anterior lower labial and gingival mucosa (figure 1).

Investigations

Laboratory investigations demonstrated a slight lymphopenia (0.8), mild aminitis (AST (aspartate aminotransferase) 102.0 U/L, ALT (alanine aminotransferase) 61.0 U/L, ALP (alkaline phosphatase) 79.0 U/L; bilirubin normal) and elevated ferritin (1931.0 ug/L); syphilis serologies were negative. Toxicology was positive for tetrahydrocannabinol (THC) only. MRI with contrast showed no acute or chronic abnormalities. A cutaneous biopsy of a papulonodule demonstrated focal interface change, superficial and deep dermal perivascular and interstitial lymphoeosinophilic infiltrates with no evidence of vasculitis, compatible with resolving erythema multiforme. Swabs of the oral mucosal erosions were negative for herpes simplex virus (HSV) and varicella zoster virus by PCR.

Differential diagnosis

The possibility of cannabis-induced psychosis was entertained, however the patient had never experienced similar recations to other antihistamine medications with or without cannabis usage, which he had been smoking roughly 0.9 g per day for several years without dose or source change. A major depressive episode with psychotic features was also entertained as a diagnostic possibility, but was deemed less likely given the acute onset, cetirizine re-challenge evidence and rapid resolution of psychotic symptoms with only low doses of pharmacotherapy.

The differential diagnosis of the cutaneous eruption, given the histology, includes a fixed-drug eruption and arthropod bites, however the clinical scenario including mucosal ulceration, histopathological interface change and prior viral infectious process largely favours erythema multiforme.

Treatment

To manage his depression and acute psychotic symptoms, the patient was started on sertraline 50 mg and aripiprazole 5 mg one time per day, respectively. His pruritic eruption was managed with topical 0.05% betamethasone valerate cream two times per day as needed to affected areas for itch.

Outcome and follow-up

Over the course of the 5-day admission, he was compliant with treatment and his hallucinations and paranoid delusions resolved entirely. He quickly gained insight into his psychotic symptoms and described being aware of experiencing ‘hallucinations’ on both occasions shortly after taking cetirizine. He was advised to continue his antipsychotic and antidepressant medications for at least 6 months and avoid cetirizine indefinitely. He was also counselled on the risk of ongoing cannabis use in precipitating psychosis. His mother had visited him on the unit and indicated that he had returned to his baseline and had no safety concerns. Eight-weeks post discharge, the patient continued to deny any psychotic symptoms despite resumption of cannabis use and the mucocutaneous eruption had resolved.