Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases.

Andrea Toniato,Chiara Gamba,Elide Anna Pastorello,Michele Nichelatti,Marta Piantanida,Linda Borgonovo,Joseph Scibilia,Emanuela Bonoldi,Valentina Caputo,Valeria Fabbri,Jan Walter Schroeder,Scarlett Valeria Bernal Ortiz,Luca Balossi,Eleonora Brusamolino

doi:10.3390/ijms22137072

Andrea Toniato, Chiara Gamba + Show 12 more

Open Access

https://doi.org/10.3390/ijms22137072

Copy DOI

Abstract

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p = 0.0067) and an age of at least 68 years (p = 0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Highlights

DRESS/DiHS is a complex and potentially fatal drug reaction that includes skin rash, eosinophilia, atypical lymphocytosis, lymphadenopathy, fever, and systemic organ involvement [1].Its incidence is about 10 cases per 1 million inhabitants [1]
The reasons for the uncertainty were derived not so much from the lack of key aspects for DRESS such as skin rash, eosinophilia, and organ involvement, but especially from the impossibility to exclude all those conditions that enter in differential diagnosis with DRESS according to RegiSCAR criteria for the lack of the results [11,12]
We found that the number of medications in therapy prior to DRESS conditioned the severity of the reaction

Summary

Introduction

DRESS/DiHS is a complex and potentially fatal drug reaction that includes skin rash, eosinophilia, atypical lymphocytosis, lymphadenopathy, fever, and systemic organ involvement [1].Its incidence is about 10 cases per 1 million inhabitants [1]. DRESS/DiHS is a complex and potentially fatal drug reaction that includes skin rash, eosinophilia, atypical lymphocytosis, lymphadenopathy, fever, and systemic organ involvement [1]. The immune mechanism is a IVb cell-mediated reaction, in which activated Th2 cells act by recruiting eosinophils. An important role is played by genetic predisposition conferred by particular polymorphisms in HLA genes with respect to specific drugs, like HLA-B*58:01 for allopurinol, HLA-A*31:01 for carbamazepine, and HLA-B*57:01 for abacavir [4]. Other mechanisms involve altered drug detoxification or sequential reactivation of herpesviruses, such as human herpesvirus type 6 (HHV-6) and cytomegalovirus (CMV), and the subsequent antiviral immune response, which all appear to be associated with the systemic manifestations of DRESS [6]

Objectives

Methods

Results

Discussion

Conclusion