Acta Dermato-Venereologica 98-4CompleteContent | Page 7

401 CLINICAL REPORT Clinical, Viral and Genetic Characteristics of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in Shanghai, China Xiaojin WU 1 , Fanping YANG 1 , Shengan CHEN 1 , Hao XIONG 1 , Qinyuan ZHU 1 , Xudong GAO 1 , Qinghe XING 2 and Xiaoqun LUO 1 1 Department of Dermatology, Huashan Hospital, Fudan University, and 2 Children’s Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prog- nostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral cen- tre in Shanghai, China, from January 2011 to Decem- ber 2016, were analysed retrospectively. All the pa- tients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511  ±  3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carba- mazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA- B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein- Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associa- ted with autoimmune sequelae. Due to its high medi- cal cost and sometimes poor prognosis, prevention of DRESS should be a high priority. Key words: drug reaction with eosinophilia and systemic symp­ toms; drug hypersensitivity; adverse drug reaction; human herpes virus; human leukocyte antigen. Accepted Dec 14, 2017; Epub ahead of print Dec 15, 2017 Acta Derm Venereol 2018; 98: 401–405. Corr: Xiaoqun Luo, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China. E-mail: [email protected] D rug reaction with eosinophilia and systemic symp- toms (DRESS), or drug-induced hypersensitivity syndrome (DIHS), ranks among the most severe cuta- neous drug reactions and may be life-threatening. Apart from extreme eosinophilia and organ dysfunction, its cha- racteristics include a long latent period, fever, skin rash and lymphadenopathy. Because of its complex natural course and various clinical manifestations, it is difficult to make a diagnosis of DRESS. In 2007, the European registry of severe cutaneous adverse reactions (RegiS- CAR) established the diagnostic criteria for DRESS (1) and thus clarified the definition. During the past decade, numerous studies have repor- ted genetic predispositions of severe cutaneous adverse reactions (SCARs). Correlations between multiple human leukocyte antigen (HLA) alleles with specific drug-indu- ced SCARs have been identified (2). For example, HLA- B*5801 has a strong correlation with allopurinol (ALP)- induced SCARs in Thai and Han Chinese populations (3, 4). The negative predictive value of HLA-B*5801 was high, although its positive predictive value was compa- ratively low (3, 5). This means that many ALP-tolerant patients also carry this allele. Moreover, very few studies have analysed the associations between HLA alleles and each subtype of SCARs. Due to its low incidence, a large population analysis concerning the association between the HLA allele and DRESS is currently lacking. Apart from genetic predisposition, reactivation of the human herpes virus (HHV) family also plays a key part in the pathogenesis of DRESS. However, the role of the HHV family is controversial. Some authors report that DRESS is the consequence of viral reactivation (6), while others regard these infections as complications of immunosuppressive therapy (7). Previous studies have observed an association between HHV6 reactivation and the severity of DRESS (8, 9). However, the role of virus reactivation in the natural chronic course of DRESS and in relapses remains hypothetical (10). Large-scale retro- spective studies analysing the relationship between HHV reactivation and the prognosis of DRESS are limited. The aim of the current study was to analyse the most common culprit drugs, latent period and medical cost of Chinese patients with DRESS. Particular attention was paid to the genetic predisposition and prognostic factors of DRESS. METHODS Subject enrollment and sample collection Medical records of all patients hospitalized in the Department of Dermatology at Huashan Hospital affiliated to Fudan University in Shanghai, China between January 2011 and December 2016 were retrospectively reviewed. Patients diagnosed with “drug eruption” and “drug hypersensitivity syndrome” were listed as suspected DRESS patients. These patients’ whole-blood samples were pro- spectively collected within 2 days after admission unless otherwise indicated. Follow-up was accomplished via a phone interview. All patients were followed up for at least 6 month after discharge. According to RegiSCAR diagnostic criteria, patients with sus- pected DRESS were classified as definite, probable, possible, or no case. Those whose final points failed to reach 2 (defined as no case by RegiSCAR diagnostic criteria) were excluded from the study. Two control groups were recruited in this study. The first con- trol group was chosen from the human MHC database (dbMHC) (11). It consisted of 283 unrelated healthy Chinese people. The other control group consisted of patients who did not develop any This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340/00015555-2867 Acta Derm Venereol 2018; 98: 401–405