Drug-induced Hypersensitivity Syndrome Research Articles

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by sulfasalazine: a case report and literature review

Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially fatal systemic reaction characterized by multiorgan damage involving the liver, hematopoietic system and skin, and heterogeneous manifestations of fever, rash, lymphadenopathy and eosinophilia with unpredictable course.We describe a 41-year-old female patient who developed DRESS syndrome after taking sulfasalazine prescribed for non-radiographic axial spondyloarthritis. Treatment with intravenous and then oral glucocorticoids was effective. A review of the literature on this topic is presented.

Incidence of drug-induced hypersensitivity syndrome associated with levetiracetam and clobazam is likely underreported

Incidence of drug-induced hypersensitivity syndrome associated with levetiracetam and clobazam is likely underreported

Fulminant type 1 diabetes caused by DIHS could be affected by the reactivation of HHV-6.

In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear. We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6. We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases, and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D. The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In one case, HHV-6 DNA was also identified shortly before the onset of FT1D. These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS. .

Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Dapsone-Induced DRESS Syndrome: A Case Report

Drug reaction with eosinophilia and systemic symptoms DRESS syndrome sometimes known as drug-induced hypersensitivity syndrome represents a unique and potentially life-threatening adverse response triggered by medications. It typically presents as a skin rash resembling measles affecting individuals of various age groups accompanied by symptoms like fever swollen lymph nodes irregular blood cell counts and a range of multiorgan issues. Its incidence is 11000 to 10000 exposures and its mortality is 10-20. We report a case of a patient diagnosed with DRESS syndrome secondary to Dapsone use. The main objective of this case report is to describe the characteristics complications and treatment of drug-induced DRESS syndrome. The presented case report of a 17-year-old female patient admitted to a tertiary care hospital in Bengaluru with a history of peeling skin all over the body for 10 days and was diagnosed with DRESS syndrome secondary to Dapsone use. During the admission she was prescribed Wysolone and Atarax Hydroxyzine. The patient was simultaneously treated with local ointments and her condition symptomatically improved. This case emphasizes the fatal and life-threatening adverse reactions of Dapsone and their management.

Ciprofloxacin Ophthalmic DRESS Syndrome: Case Report

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is a rare severe systemic hypersensitivity drug reaction. Diagnosing DRESS syndrome is challenging due to non-specific manifestations that can make it difficult to recognize. Therefore, addressing and discussing this issue is extremely important, considering the potential lethality of a treatable syndrome. Clinical case: We describe the clinical characteristics of a 39-year-old female who presented with DRESS syndrome associated with the use of ciprofloxacin ophthalmic. The patient manifested a mild maculopapular rash located in the pelvic limbs with subsequent ascending distribution and generalized erythematoviolaceous affecting four extremities, trunk, facial region and scalp, together with fever and lymphadenopathy. Paraclinical tests revealed leukocytosis and eosinophilia. According to RegiScar's ranking, it scored 6 points, classifying it as the definitive case for DRESS. He concluded a schedule with prednisone 1 mg/kg/day with a slow reduction dose, obtaining a good response to treatment. Conclusions: DRESS syndrome should be suspected in a patient receiving medical treatment who presents with the following signs and symptoms: rash, fever (38°C), facial edema, and lymphadenopathy. Fortunately, this reaction is usually reversible, with a low incidence of residual damage or mortality, in the case of timely discontinuation of antibiotics and use of topical or systemic corticosteroids.

Drug-Induced Hypersensitivity Syndrome Combined with Hemophagocytic Lymphohistiocytosis related to Piperacillin-Tazobactam: A Case Report.

Drug-Induced Hypersensitivity Syndrome Combined with Hemophagocytic Lymphohistiocytosis related to Piperacillin-Tazobactam: A Case Report.

Atypical Intralymphatic T-Cell Proliferation during DRESS Mimicking Intravascular Lymphoma: Case Report

Drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced reaction that represents a life-threatening condition. The histopathologic appearance of the skin biopsy is nonspecific but may exceptionally show an atypical intralymphatic lymphocytic infiltrate, and mimic an intravascular lymphoma. Through this article, we will report an exceptional case of a patient presenting with skin lesions pointing to a dress, but whose histological appearance, in the presence of adenopathy during physical examination, can lead, by mistake, to the diagnosis of an intralymphatic lymphoma. We aim to highlight the various diagnostic indices allowing the distinction between these two entities, including the immunohistochemical study, the search for the TcR clonal rearrangement and the anatomo-clinical correlation.

Fulminant type 1 diabetes: Focusing on triggering factors.

Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic β cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.

Drug-Induced Hypersensitivity Syndrome/Drug Reaction With Eosinophilia and Systemic Symptoms: Predictive Score and Outcomes.

We previously developed a drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity (DDS) score that may predict DIHS/DRESS-associated complications (DACs), including myocarditis, gastrointestinal bleeding, and autoimmune diseases. To externally confirm the predictive accuracy of the DDS score, clarify its ability to identify patients at high risk of DACs and fatal outcome, and determine which treatments might reduce or increase the risk. We conducted a nationwide multicenter retrospective study in which we followed 48 patients with DIHS/DRESS at 5 university hospitals in Japan for 1 year after onset. Patients were divided into mild, moderate, and severe DIHS/DRESS groups depending on their early DDS score. Eight cases had DACs in the severe group (n= 17); no DACs were observed in the mild group (n= 12). Receiver-operating characteristic curve analysis showed that a cutoff DDS score of ≥4.0 and ≤2.0 could differentiate patients who would and would not develop DACs, respectively. In the moderate-to-severe disease groups, DACs occurred only in patients who received corticosteroids and not in those who received supportive care. None of the patients who received early treatment for cytomegalovirus developed DACs. Autoimmune DACs were significantly more common in patients who received pulse corticosteroid therapy. Four deaths occurred within the 1-year follow-up; all were in patients with infectious DACs who received systemic corticosteroids. Our scoring system allows early identification of patients at increased risk for DACs. Risk factors for DACs include systemic or pulse corticosteroid therapy.

Immune Reactions in Major Types of Oncological Treatment.

In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.

Dapsone hypersensitivity syndrome.

Dapsone hypersensitivity syndrome.

Advances in understanding of the pathogenesis and therapeutic implications of drug reaction with eosinophilia and systemic symptoms: an updated review.

Drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome (DRESS/DIHS) is one type of severe cutaneous adverse reaction (SCAR). It is featured by fever, widespread skin lesions, protracted clinical course, internal organ involvement, and possibly long-term autoimmune sequelae. The presence of high-risk human leukocyte antigen (HLA) alleles, hypersensitivity reaction after culprit drug ingestion, and human herpesvirus reactivation may all contribute to its complex clinical manifestations. Some recent studies focusing on the roles of involved cytokines/chemokines and T cells co-signaling pathways in DRESS/DIHS were conducted. In addition, some predictors of disease severity and prognosis were also reported. In this review, we provided an update on the current understanding of the pathogenesis, potential biomarkers, and the relevant therapeutic rationales of DRESS/DIHS.

Fulminant Type 1 Diabetes-East and West.

Fulminant type 1 diabetes is a subtype of type 1 diabetes in which beta cells are destroyed within days or a few weeks. The first criterion indicates a rise in blood glucose levels shown in the patient's history. The second suggests that the increase occurs suddenly within a very short period, as shown by the laboratory findings of the discrepancy between the glycated hemoglobin concentration and plasma glucose level. The third indicates a marked reduction in endogenous insulin secretion, which indicates almost complete destruction of beta cells. Fulminant type 1 diabetes is a common subtype in East Asian countries, including Japan, but rare in Western countries. Class II human leukocyte antigen and other genetic factors may have contributed to the skewed distribution. Environmental factors may also be involved including entero and herpes viruses and immune regulation during drug-induced hypersensitivity syndrome; pregnancy may also affect it. In contrast, treatment with an immune checkpoint inhibitor of the anti-programmed cell death 1 antibody induces similar characteristics and incidence of diabetes as fulminant type 1 diabetes. Further studies are needed to clarify the etiology and clinical characteristics of fulminant type 1 diabetes. Although the incidence of this disease differs between the East and West, it is life-threatening; thus, it is important to diagnose fulminant type 1 diabetes without delay and treat it appropriately.

Atypical drug-induced hypersensitivity syndrome with multiple organ failure rescued by combined acute blood purification therapy: a case report

BackgroundDrug-induced hypersensitivity syndrome (DIHS), including Stevens-Johnson syndrome (SJS), is a severe rash that often develops 2–6 weeks after the intake of the causative drug; however, its diagnosis is sometimes difficult. This article describes a case in which a patient with DIHS-induced multiple organ failure was successfully treated with blood purification therapy.Case presentationA male patient in his 60s was admitted to our hospital with autoimmune encephalitis. The patient was treated with steroid pulse therapy, acyclovir, levetiracetam, and phenytoin. From the 25th day, he presented with fever (≥ 38 °C) as well as miliary-sized erythema on the extremities and trunk, followed by erosions. DIHS and SJS were suspected; accordingly, levetiracetam, phenytoin, and acyclovir were discontinued. On the 30th day, his condition further deteriorated, and he was admitted to the intensive care unit for ventilatory management. The next day, he developed multi-organ failure and was started on hemodiafiltration (HDF) for acute kidney injury. Although he presented with hepatic dysfunction and the appearance of atypical lymphocytes, he did not meet the diagnostic criteria for DIHS or SJS/toxic epidermal necrolysis. Therefore, he was diagnosed with multi-organ failure caused by severe drug eruption and underwent a 3-day treatment with plasma exchange (PE) in addition to HDF. Accordingly, the patient was diagnosed with atypical DIHS. After being started on blood purification therapy, the skin rash began to disappear; moreover, the organ damage improved, with a gradual increase in urine output. Eventually, the patient was weaned off the ventilator and transferred to the hospital on the 101st day.ConclusionsHDF + PE could effectively treat multi-organ failure caused by atypical DIHS, which is difficult to diagnose.

1436 Lesional skin histology in drug-induced hypersensitivity syndrome: A single center 10-year experience of 37 patients

1436 Lesional skin histology in drug-induced hypersensitivity syndrome: A single center 10-year experience of 37 patients

344 TNFα-induced vascular hyperpermeability as the possible cause of purpura in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS)

344 TNFα-induced vascular hyperpermeability as the possible cause of purpura in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS)

DRESS, una reacción alérgica no mediada por IgE

DRESS (drug reaction syndrome with eosinophilia and sys¬temic symptoms) is a rare drug-induced multisystemic hy-persensitivity response that can induce a severe cutaneous adverse reaction that is difficult to diagnose and treat. It fre-quently manifests as an extensive skin rash, systemic symp¬toms, lymphadenopathy, visceral organ involvement, and hematological alterations, mainly leukocytosis, eosinophilia, and sometimes atypical lymphocytosis that manifest 2 to 8 weeks after continuous administration of the responsible drug. The most prevalent drugs related with this syndrome are phenytoin, carbamazepine, allopurinol, and abacavir. Some specific human leukocyte antigen (HLA) alleles have been identified that are associated with hypersensitivity to these drugs. The pathophysiology of DRESS syndrome is not yet fully understood; the main hypothesis is a T-cell me¬diated hypersensitivity response when interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. The criteria of the European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) are the most commonly used for the diagnosis of DRESS syndrome. Drug-induced hypersensitivity syndrome (DiHS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) should be considered for any rash that appears following the administration of any drug. Therapy of this condition includes the elimination of the causative agent as soon as possible, as well as systemic corticosteroids which remain the mainstay of treatment of DRESS with in-ternal organ involvement. Steroid-sparing agents such as cyclosporine, intravenous immunoglobulins (IVIGs), and other immunosuppressive agents have been used successfully to contribute to treatment. Keywords: DRESS; drug hypersensitivity syndrome; adverse drug reactions; hypersensitivity reaction; eosinophilia.

DRESS/DiHS syndrome induced by Propylthiouracil: a case report

BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome.Case presentationA 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later.ConclusionsPropylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.