(138) Running Out of Options: A Case of DRESS with Possible Neosensitization to Lurasidone in an Acutely Manic, Psychotic, and Catatonic Patient

Abstract:

Background:
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a serious and potentially fatal medication-induced hypersensitivity syndrome characterized by rash, edema, eosinophilia, thrombocytopenia, lymphocytosis/lymphopenia, lymphadenopathy, and systemic symptoms including fever, rigors, and hypotension. Patients frequently develop cross-reactivity to other medications administered during or after an episode of DRESS (Issacs, 2018). We report a case of DRESS with possible neosensitization to lurasidone in an acutely manic and psychotic patient, further complicated by catatonia.

Case:
Ms. Y, a 43-year-old woman with bipolar disorder, presented in acute mania with psychotic features. Olanzapine, initiated for mood stabilization and psychosis, was later titrated to risperidone and valproate given poor response. Mid-titration, she developed morbilliform rash with facial edema, cervical lymphadenopathy, fever, pancytopenia, and transaminitis, consistent with DRESS. All three agents were discontinued and intravenous steroids were administered. She subsequently developed severe catatonia, presenting completely mute and rigid with Bush-Francis score of 24/69, prompting initiation of lorazepam. Lurasidone trial for re-emergent mania was quickly discontinued due to rash recurrence. Lithium was ineffective due to oral medication refusals. Chlorpromazine was initiated slowly, with good effect. After a prolonged course, catatonia resolved and lorazepam was slowly tapered. Once oral medications were tolerated, chlorpromazine was titrated to lithium monotherapy with good effect.

Discussion:
Neosensitization is caused by massive non-specific immune system activation which enhances antigen presentation and leads to decreased drug tolerance (Song, 2017). It may occur with medications given during the DRESS episode or medications structurally related to the initial offending agent. The original culprit drug in this case was likely valproate and/or olanzapine, which have both been implicated in DRESS (Penchilaiya, 2017). Though the lurasidone-associated rash may have been due to DRESS relapse, which can occur even weeks following withdrawal of the offending agent (Isaacs, 2018), neosensitization to lurasidone is suspected given structural similarities to olanzapine and risperidone. Concern for additional neosensitization further complicated medication selection in this complex case. Ultimately, chlorpromazine was chosen due to no reports of neosensitization, avoidance of iatrogenically worsening catatonia, and requirement for non-oral administration.

Conclusion:
Neosensitization is a rare but important risk associated with DRESS and should be considered when symptoms of DRESS recur in the absence of the initial culprit drug. Additionally, risk of neosensitization should be considered when selecting new psychotropics following an episode of DRESS.

References:

1. Isaacs M. DRESS syndrome: clinical myths and pearls. Cutis. 2018;102(5):322-326.


2. Penchilaiya V, et. al. DRESS syndrome: Addressing the drug hypersensitivity syndrome on combination of Sodium Valproate and Olanzapine. Asian J Psychiatr. 2017;28:175-176. doi:10.1016/j.ajp.2017.05.015


3. Song JM, et. al. Neosensitization to Multiple Drugs Following Valproate-Induced Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome. Psychiatry Investig. 2017;14(4):518-520. doi:10.4306/pi.2017.14.4.518