Drug reaction with eosinophilia and systemic symptoms (DRESS): incidence,pathogenesis and management

Introduction: Drug-induced hypersensitivity syndrome(DiHS), often referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a life-threatening multi-organ system reaction induced by drugs and associated with sequential reactivations of herpesviruses. This syndrome has several unique features, creating uncertainty over whether it represents true drug eruption.

Areas covered: A literature review of all the cases was made by a Pub Med search. The delayed onset, paradoxical worsening of clinical symptoms after withdrawal of the causative drug and unexplained cross-reactivity to multiple drugs are unique features of this syndrome, which could prompt infection to be an initial consideration. Regulatory T cells (Tregs) are expanded at the acute stage but, upon clinical resolution, their function become gradually defective. Because such a gradual loss of Treg function occurring after resolution of DiHS/DRESS could increase the risk of developing autoimmune sequelae, systemic corticosteroids administered during the acute stage may serve to prevent not only tissue damage but also the gradual loss of Treg function by restoring the impaired Treg activity.

Expert opinion: Systemic corticosteroids give promising results in terms of not only alleviating a variety of clinical symptoms at the acute stage but also of preventing the generation of autoimmune responses occurring at the resolution stage.     

Drug reaction with eosinophilia and systemic symptoms without skin rash

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal.KEY WORDS: Absence of skin lesions, drug reaction with eosinophilia and systemic symptoms, salazopyrin     

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.     

万古霉素致DRESS综合征22例文献分析

目的:分析万古霉素致伴嗜酸性粒细胞增多和系统症状的药疹综合征(DRESS综合征)的发生规律及特点,为安全用药提供参考。方法:检索国内外库收载的万古霉素致DRESS综合征文献进行分析。结果:共筛选出有效个案报道15篇,22例患者,其中男14例,女8例,青少年2例。用药至发生DRESS综合征的平均时间为3周。临床表现主要为皮疹、发热、嗜酸性粒细胞增多并累及多器官损伤,最常见受累的器官为肝脏(16例,72.7%)。结论:临床医师应了解万古霉素致DRESS综合征的规律和特点,加强用药监测,以便及时发现和处理DRESS综合征。     

1例替加环素致皮疹伴嗜酸粒细胞增多报道

1例59岁男性因腹主动脉支架植入和右肾动脉支架植入术后肺部感染,根据病原学回报结果给予替加环素(首次剂量100 mg,随后50 mg,每12小时1次,静脉滴注)抗感染治疗。用药第8天,患者双下肢出现散在大小不等红色斑疹,界限欠清楚,形态欠规则,表面光滑干燥,局部融合成片,压之褪色。次日皮疹较前明显加重,范围扩大遍及全身,无破溃。自应用替加环素至皮疹发生,患者嗜酸性粒细胞计数始终高于正常值,波动在1.03×10~9·L~(-1)至1.27×10~9·L~(-1)之间。对其用药进行梳理分析,考虑替加环素引起的过敏反应,遂予以停用替加环素并进行抗过敏治疗。随后患者皮疹明显减轻至痊愈,同时嗜酸性粒细胞逐渐下降恢复至正常。因此,临床应用替加环素时应高度警惕皮疹的发生,确保安全用药。     

来那度胺致药物超敏反应综合征1例

1 病例资料 患者,女,62岁.因全身起红色斑丘疹、颜面水肿伴发热1月余于2020年2月14日入院.患者2月前在外院诊断为多发性骨髓瘤(multiple myeloma,MM),50 d前开始接受为期28 d的VRD(硼替佐米+来那度胺+地塞米松)方案化疗:注射用硼替佐米2.1 mg第1,4,8,11天皮下注射,来那度...     

伴嗜酸性粒细胞增多和系统症状的药疹诊治进展

伴嗜酸性粒细胞增多和系统症状的药疹(DRESS)是一种危及生命的皮肤严重药物不良反应综合征,临床诊断困难且死亡率高.发病机制可能与特异性药物、免疫应答的改变、疱疹病毒再次激活以及HLA复合体的遗传易感性等多种因素相关.本文简要综述DRESS的诊治进展.     

Carbamazepine-induced severe systemic hypersensitivity reaction with eosinophilia

Skin rash, fever, and eosinophilia developed in a previously healthy 35-year-old woman three weeks after starting carbamazepine. Fulminant respiratory and renal failure ensued. Autopsy showed pneumonitis, nephritis, serositis, pancreatitis, hepatitis, and carditis, characterized by an infiltrate of eosinophils and lymphocytes. The severity, duration, and extensive organ involvement of the reaction make this case unique.     

The effects of fexofenadine on eosinophilia and systemic anaphylaxis in mice infected with Trichinella spiralis

BACKGROUND: The effects of the non-impairing, H(1)-receptor antagonist fexofenadine were investigated in in vivo mouse models of eosinophilia and systemic anaphylaxis. METHODS: Eosinophilia was investigated in C57BL/6 mice (n=5 per group) infected with Trichinella spiralis, with and without administration of fexofenadine HCl (5, 10 and 20 mg/kg/day). Eosinophilia was also studied, with and without fexofenadine administration, in mice with a congenital mast-cell deficiency (W/W(v)) and controls (+/+). The effect of fexofenadine HCl (20 mg/kg/day) on IL-5 and eotaxin blood levels was also investigated in C57BL/6 mice. In a separate model, systemic anaphylaxis was induced in C57BL/6 mice using T. spiralis antigen. Fexofenadine HCl (5, 10 and 20 mg/kg) or vehicle was administered 20 min before antigen challenge (n=5 per group). The effect of fexofenadine on systemic anaphylaxis caused by IgE and anti-IgE was also examined in CBF1 mice injected with serum from NC/Nga mice with high IgE levels. Rectal temperature was measured as an indicator of anaphylaxis. RESULTS: In C57BL/6 mice, repetitive oral administration of fexofenadine HCl (5, 10 and 20 mg/kg/day) resulted in dose-dependent suppression of eosinophilia (p<0.05-0.0001). No suppression was observed in mast-cell deficient W/W(v) mice. In addition, single oral administration of fexofenadine HCl (10 and 20 mg/kg) significantly suppressed the decrease in rectal temperature (p<0.01), a marker for systemic anaphylaxis, in C57BL/6 mice. In CBF1 mice injected with serum from NC/Nga mice with high IgE levels, the decrease in rectal temperature was suppressed by single administration of fexofenadine HCl (10 and 20 mg/kg; p<0.01 and p<0.001, respectively). Fexofenadine had no effect on peripheral IL-5 and eotaxin levels. CONCLUSION: These results indicate that fexofenadine suppresses both eosinophilia and systemic anaphylaxis, both of which are fundamental reactions in allergic diseases.     

肺炎支原体感染致皮肤表现86例

目的探讨儿童肺炎支原体(MP)感染致皮肤损害的特点。方法感染患儿506例,采用间接免疫荧光法进行5种病原体联检。观察血清MP-IgM阳性伴皮肤损害患儿的临床资料。结果 506例MP-IgM阳性患儿中,86例在呼吸道感染的基础上伴皮肤损害,其中表现荨麻疹样皮疹36例,红斑或斑丘疹20例,猩红热样皮疹13例,紫癜样皮疹8例,麻疹样皮疹6例,水疱疹3例。阿奇霉紊针静脉滴注3～5d,之后换用罗红霉素口服2～3周,皮疹均在数小时至14d内消失,预后好。结论 MP感染不仅是呼吸道感染的重要病原体,也可致皮肤损害,呼吸道感染并有皮肤损害的病例,要考虑到MP感染的可能。     

糖皮质激素联合羟氯喹治疗系统性红斑狼疮皮疹的临床效果

目的 分析和评价糖皮质激素联合羟氯喹治疗系统性红斑狼疮皮疹的临床效果.方法 选取2020年1月至12月上饶市人民医院收治的60例系统性红斑狼疮皮疹患者作为研究对象,患者均为女性.按照人院顺序单双号分为对照组和研究组,每组30例,对照组采取单一的糖皮质激素进行治疗,研究组采取糖皮质激素联合羟氯喹的方式进行治疗,比较两组的...     

非过敏性鼻炎伴嗜酸性粒细胞增多症鼻通气主观症状与鼻通气功能相关性研究

目的：对非过敏性鼻炎伴嗜酸性粒细胞增多征（ NARES）患者鼻通气主观症状与鼻通气功能相关性进行分析，从而为其临床诊断提供依据。方法选择NARES患者44例作为NARES组，并以同期健康体检者50例作为对照组。比较两组鼻总阻力值（TNR）、最小横截面积（MCA），并对NARES患者主观症状及客观检测指标进行Pearson或Spearman相关性分析。结果收缩前，NARES组在75 Pa和150 Pa TNR均高于健康对照组（Mann-Whiteny Z＝7．365、8．125，均P＜0．05）；收缩后，两组75 Pa和150 Pa TNR差异、MCA差异、NARES 8个主观症状与7个客观指标相关性分析，差异均无统计学意义（均P＞0．05）。结论非过敏性鼻炎伴嗜酸性粒细胞增多征患者鼻通气功能与主观症状之间相关性不明显，临床诊断应全面进行，以防漏诊和误诊。     

Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs

Trimellitic anhydride (TMA) causes asthma after a latency period of sensitization. In non-sensitized humans and animals, limited studies indicate that TMA exposure may also cause symptoms of asthma without a latency period. Our previous studies (J. Pharmacol. Exp. Ther. 296 (2001) 284) in a guinea pig model of TMA-induced asthma demonstrated that sensitization and the complement system were required for eosinophilia. TMA conjugated to guinea pig serum albumin (TMA-GPSA) was used to elicit the response. Since occupational exposure to TMA occurs by inhalation of dust, the present studies determined if exposure to TMA dust in a non-sensitized guinea pig elicited airway obstruction and inflammation, and whether a significantly greater response occurred after a latency period of sensitization. Guinea pigs were intradermally injected with either corn oil (non-sensitized animals) or 30% TMA (sensitized animals). Three weeks later they were challenged by intratracheal insufflation with 1 mg TMA dust or lactose dust (control) using a dry powder delivery device. Pulmonary resistance, dynamic lung compliance, mean arterial blood pressure and heart rate were monitored for 10 min. In non-sensitized guinea pigs, significant increases in pulmonary resistance and decreases in dynamic lung compliance and blood pressure occurred after TMA challenge. In sensitized animals, the same dose of TMA caused significantly greater effects compared to non-sensitized animals. In a separate experiment, cellular infiltration into the lung was determined 24 h after challenge with TMA dust or lactose dust. In both non-sensitized and sensitized animals, eosinophils in the lung tissue were increased after TMA dust challenge compared to controls. Thus, these studies suggest that the response in non-sensitized animals differs depending on whether TMA dust or TMA-GPSA is used to elicit the response. TMA dust elicits significant airway obstruction and eosinophilia in a non-sensitized animal, with even greater airway obstruction occurring in a sensitized animal.     

Adult fetal alcohol syndrome (FAS) with various nouropsychiatric symptoms]

This is the first report of an adult patients with the fetal alcohol syndrome (FAS) in Japan, who was treated for psychiatric disorders. The case was a 35 years-old woman who had many neuropsychiatric symptoms. She had been treated for 15 years at the Kurihama Alcoholism Center, for mental retardation, schizophrenic symptoms, attention deficit hyperactivity disorder, learning disorder, trichotillomania, bipolar disorder, and impulsive behavior. She had low body weight at birth, mental retardation and a small facial malformation, which were diagnosed as FAS. At first admission, she was not diagnosed as FAS because her parent denied that her mother drank during pregnancy. Recently, her family admitted her mother's heavy drinking during pregnancy, and we diagnosed her as having FAS. She showed many pathological symptoms of the central nervous system such as very lower scores for performance IQ than for verbal IQ in the WAIS-R and enlargement of the lateral ventricle on MRI. Recently many reports have mentioned that prenatal alcohol exposure brings about severe damage of the central nervous system. Therefore, one author proposes that such disorders are referred to as fetal alcohol spectrum disorders (FASD). This patient showed many symptoms of FASD, and was difficult to treat because of these symptoms.