Clozapine-Induced DRESS Syndrome: A Case Series From the AMSP Multicenter Drug Safety Surveillance Project

Sanader, Bruna; Grohmann, Renate; Grötsch, Philipp; Schumann, Thomas; Toto, Sermin; Fernando, Piyumi; Stübner, Susanne

doi:10.1055/a-0586-8983

Cited by 17 publications

(18 citation statements)

References 7 publications

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“…The phenomenon observed in these patients was secondary to the inflammatory process leading to an increase in circulatory levels of clozapine. It is known that cytokines can inhibit the metabolism of clozapine through cytochrome 4501A2 inhibition (87).…”

Section: Clozapinementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

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Section: Clozapinementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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“…Afterward, 16 of them were excluded because they were classified as possible (n = 13, 30.2%) or no case (n = 3, 7%). A reference list for papers classified as no cases or possible is included in the Supplementary (Belloni et al, 2007;Benning, 1998;Bugge et al, 2016;Fehily et al, 2016;Lebrun et al, 2018;Lim et al, 2003;Masopust et al, 2009;Merrill et al, 2006;Mohan et al, 2013;Mukherjee et al, 2019;Pelizza and Melegari, 2007;Rhee et al, 2019;Sanader et al, 2019;Trincas et al, 2017) (S4 Reference list). Lastly, 27 patients reported in 26 publications scored as probable (n = 23, 53.5%) or definite DRESS (n = 4, 9.3%) were included in the review (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…Clozapine daily doses ranged between 75 and 400 mg (Ben-Ari et al, 2008;Dimitri Valente et al, 2018) (median 200 mg, n = 20). Blood clozapine levels were available only for two patients (Luo et al, 2007;Sanader et al, 2019); in both cases levels were above the laboratory alert level (1000 ng/mL) (Luo et al, 2007;Sanader et al, 2019). Elevated c-reactive protein (CRP) levels were reported in six patients (22.2%) (Dimitri Valente et al, 2018;Manfredi and Sabbatani, 2007;Parekh et al, 2014;Pathak et al, 2019;Sanader et al, 2019) (Supplemental Table S6).…”

Section: Demographic and Clinical Baseline Characteristicsmentioning

confidence: 99%

“…Blood clozapine levels were available only for two patients (Luo et al, 2007;Sanader et al, 2019); in both cases levels were above the laboratory alert level (1000 ng/mL) (Luo et al, 2007;Sanader et al, 2019). Elevated c-reactive protein (CRP) levels were reported in six patients (22.2%) (Dimitri Valente et al, 2018;Manfredi and Sabbatani, 2007;Parekh et al, 2014;Pathak et al, 2019;Sanader et al, 2019) (Supplemental Table S6). Interferon gamma and human herpesvirus (HHV) 6 and 7 were evaluated only in two patients (4.8%) (Ben-Ari et al, 2008;Moazez et al, 2018) (Supplemental Table S6).…”

Section: Demographic and Clinical Baseline Characteristicsmentioning

confidence: 99%

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Unravelling cases of clozapine-related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients reported otherwise: A systematic review

et al. 2021

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Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug-induced hypersensitivity reaction. Aims: Aim was to review reports of clozapine-related reactions fulfilling the registry of severe cutaneous adverse reaction (RegiSCAR) criteria for DRESS syndrome reported as such or otherwise, to provide a descriptive overview of demographic patterns, clinical manifestations, and DRESS course and investigate associations between demographic, DRESS parameters, and clinical outcomes. Methods: This review was conducted following preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (registration number CRD42020156385). We searched PubMed/Embase/PsychInfo/Cochrane for reports of clozapine-related reactions meeting RegiSCAR criteria. Associations between RegiSCAR scores and time-to-recovery with demographic/clinical variables were assessed. Demographic/clinical characteristics of patients with versus without reported DRESS were compared using non-parametrical tests. Results: We identified 26 reports of 27 patients meeting RegiSCAR criteria. Males ( n = 19, 70.4%) and patients with schizophrenia ( n = 18, 66.7%) were mainly affected. Twelve patients (44.4%) received clozapine-monotherapy. DRESS symptoms manifested within a month after clozapine initiation ( n = 24, 88.9%). Lungs and liver were the most common organs involved ( n = 12, 44.4%; n = 11, 40.7%), with a mean time to recovery of 33.75 days. Clozapine rechallenge led to DRESS recurrence in four patients. Death rate was 7.4%. No associations were detected between RegiSCAR criteria or days to recovery with any demographic/clinical variables. No differences between patients with versus without reported DRESS were detected. Conclusions: Clozapine-related DRESS may be rare, but also underreported. Clinicians need to be aware of it even in patients under clozapine-monotherapy or without skin rash.

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“…31 Several cases of DRESS have been reported in clozapine-treated patients. [32][33][34] The pathogenesis of DRESS has been hypothesized to be a complex interaction of accumulation of drug metabolites caused by a genetic deficiency of metabolizing enzymes, drug hypersensitivity associated with specific human leukocyte antigen genotypes, and possible virus-drug interactions. 31 It can be speculated whether DRESS and benign and transient clozapine-induced eosinophilia share some similarities.…”

Section: Discussionmentioning

confidence: 99%

Clozapine-Related Diarrhea and Colitis

Rask¹,

Luoto²,

Solismaa³

et al. 2020

J Clin Psychopharmacol

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Background: During clozapine treatment, diarrhea is a rare but clinically relevant adverse effect. Cases of microscopic colitis and eosinophilic colitis have been previously reported.Procedures: We present 4 patients who developed severe diarrhea in early weeks of clozapine therapy.Findings: Two patients had significant peripheral eosinophilia 1 week after diarrhea symptoms. One of these patients also had Charcot-Leyden crystals in stool afterward, confirming the presence of eosinophils in the gut lumen. One of our patients had a confirmed microscopic colitis and later also neutropenia, which required treatment.Conclusions: Charcot-Leyden crystals in stool may be associated with concurrent diarrhea and eosinophilia during clozapine treatment, which is a previously unreported finding. Occurrence of blood dyscrasias with diarrhea symptoms during clozapine treatment needs further investigation to understand the possible shared mechanisms.

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Clozapine-Induced DRESS Syndrome: A Case Series From the AMSP Multicenter Drug Safety Surveillance Project

Cited by 17 publications

References 7 publications

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Unravelling cases of clozapine-related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients reported otherwise: A systematic review

Clozapine-Related Diarrhea and Colitis

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