Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a systematic review

ABSTRACT

Introduction

The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe, multiorganic, and potentially life-threatening drug-induced hypersensitivity reaction, linked to several common drugs, including antiepileptics, antibiotics, and several psychotropic drugs, including clozapine. Due to the importance of clozapine in the management of treatment-resistant schizophrenia, a systematic review and characterization of clozapine-related DRESS syndrome is long overdue.

Areas covered

This systematic review was conducted following PRISMA guidelines. PubMed, Embase, PsychINFO, and the Cochrane Library databases were independently reviewed up to 1 November 2019 for articles reporting clozapine-related DRESS syndrome cases. The RegiSCAR score system was applied to systematically characterize the clinical presentations of selected studies.

Expert opinion

Clozapine-related DRESS syndrome was reported in six patients from four articles. Five patients received polypharmacy. Skin rash and liver involvement with elevated liver enzymes were very common. No fatal cases were found. Treatment mainly included clozapine discontinuation and immunosuppression. The mismatch between incidences of DRESS with other responsible drugs, the common misdiagnosis of this syndrome, and the fact that an extensive literature search only identified six cases suggests that clozapine-related DRESS may be overlooked. It is, therefore, necessary to optimize diagnostic strategies to identify immune-related side effects of clozapine.

KEYWORDS:

• Clozapine
• dress syndrome
• antipsychotic
• drug hypersensitivity
• drug-induced reaction

Article highlights

• Recent reports implicate clozapine in Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

• Clozapine was typically implicated in DRESS in the context of polypharmacy.

• Clozapine-related DRESS syndrome may be under-reported and we hope to raise clinicians’ awareness of this risk.

Declaration of interest

J.M. Kane has been a consultant for or received honoraria from Alkermes, Dainippon Sumitomo, Eli Lilly, Forum, Allergan, Genentech, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceutica, Johnson and Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Roche, Sunovion, Takeda, and Teva. He has received grant support from Otsuka, Lundbeck, and Janssen. He has participated in advisory boards for Alkermes, Dainippon Sumitomo, Intracellular Therapies, Lundbeck, Neurocrine, Otsuka, Pierre Fabre, Takeda, and Teva. He is a Shareholder in Vanguard Research Group and LB Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.