Severe Cutaneous Adverse Drug Reactions Research Articles

Severe cutaneous adverse drug reaction to atovaquone/proguanil.

Atovaquone/proguanil is frequently prescribed among travellers to malaria-endemic areas. Side effects most commonly include headaches and gastrointestinal symptoms. Nevertheless, physicians should be aware of possible rare severe cutaneous adverse reactions, in order to facilitate the diagnosis and interrupt the drug rapidly if suspected.

Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with the presence of depression

Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with the presence of depression

Dual approaches in pharmacogenetics: Developing PCR-SSP and RT-PCR methods for HLA-B*13:01 screening to prevent dapsone and Co-trimoxazole SCARs

Dapsone and co-trimoxazole are potent antibiotics for treating various infections and inflammations. However, several studies reported the strongly association between severe cutaneous adverse drug reactions (SCARs) to both drugs and the HLA-B*13:01 allele. Rapid and reliable screening for the HLA-B*13:01 allele can mitigate the risk of dapsone-induced SCARs. We developed two methods, multiplex sequence-specific primer PCR (PCR-SSP) and real-time PCR (RT-PCR), tailored for different clinical settings. These methods were optimized to minimize false positives among the Thai population. Clinical validation demonstrated excellent reproducibility, with both methods showing 100 % concordance in repeated tests. PCR-SSP achieved a limit of detection as low as 100 pg of genomic DNA, while RT-PCR reached 1 pg. Overall statistical accuracy was 100.00 % (95 % CI: 98.18 %–100.00 %). Screening for drug-related HLA alleles is crucial for reducing mortality from severe cutaneous adverse drug reactions, especially dapsone hypersensitivity syndrome (DHS) and dapsone-induced hypersensitivity reactions (DIHRs). Our screening approach for dapsone can also be extended to co-trimoxazole, representing a significant advancement in personalized medicine and preemptive pharmacogenetic testing for tailored patient care and safety, albeit further validation in diverse ethnic populations is warranted to ensure universal applicability.

Caregiver Burden, Resilience, and Wellbeing in Cases of Severe Cutaneous Adverse Drug Reactions

Caregiver Burden, Resilience, and Wellbeing in Cases of Severe Cutaneous Adverse Drug Reactions

Caregiver Burden, Resilience, and Wellbeing in Cases of Severe Cutaneous Adverse Drug Reactions

Caregiver Burden, Resilience, and Wellbeing in Cases of Severe Cutaneous Adverse Drug Reactions

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Analysis of the Russian Database of Spontaneous Reports.

(1) Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design-a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%-TEN. In total, 30% were pediatric SRs, 21.2%-SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.

Greater mechanistic understanding of the cutaneous pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis can shed light on novel therapeutic strategies: a comprehensive review.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (SCARs) characterized by widespread epithelial detachment and blistering, which affects the skin and mucocutaneous membranes. To date, therapeutic interventions for SJS/TEN have focused on systematic suppression of the inflammatory response using high-dose corticosteroids or intravenous immunoglobulin G (IgG), for example. No targeted therapies for SJS/TEN currently exist. Though our understanding of the pathogenesis of SJS/TEN has advanced from both an immunological and dermatological perspective, this knowledge is yet to translate into the development of new targeted therapies. Greater mechanistic insight into SJS/TEN would potentially unlock new opportunities for identifying or repurposing targeted therapies to limit or even prevent epidermal injury and blistering.

Precision in Language Regarding Geographic Region of Origin in Severe Cutaneous Adverse Drug Reaction Research

Precision in Language Regarding Geographic Region of Origin in Severe Cutaneous Adverse Drug Reaction Research

Impact of antiretroviral therapy on cutaneous adverse drug reactions in adult HIV patients: A study from a tertiary care hospital

Background: Adverse drug reactions (ADRs) significantly impact public healthcare, especially among HIV patients. These reactions, which range from mild pruritus to severe conditions such as Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), affect the quality of life and treatment outcomes. Aims and Objectives: The current study was designed to evaluate the various types of cutaneous ADRs (CADRs) in adult HIV patients undergoing antiretroviral therapy (ART). Materials and Methods: A retrospective record-based study was conducted at the Department of Dermatology, Venereology, and Leprosy, Government Medical College/Government General Hospital, Suryapet, Telangana, India. Data from November 2017 to October 2020 were analyzed, focusing on patients over 18 years on ART. Relevant demographic and medical data, including blood tests, liver and renal function, and CD4 counts, were collected. Results: Out of 3532 patients on ART, 568 (16.08%) developed CADRs. Females represented 54.2% of these cases. The age group most affected was between 29 and 48 years. The most common ART regimen was Tenofovir+Lamivudin+Dolutegravir, followed by zidovudine-based combinations. Nevirapine-based regimens had a higher association with CADRs, particularly severe reactions such as SJS and TEN. Conclusion: A significant proportion of HIV patients on ART experience CADRs, with certain drug combinations posing higher risks. This study highlights the need for careful monitoring and selection of ART regimens to minimize the risk of severe CADRs, thereby improving patient outcomes and quality of life in HIV treatment.

Evaluation of severe adverse cutaneous drug reactions in patients admitted to tertiary care center: A cross-sectional study.

Adverse cutaneous drug reactions (ACDRs) are common and potentially life-threatening, while also hindering patient compliance to medications. Given the regional differences in patterns and prevalence of ACDRs, it is important to study the epidemiology, as well as the clinical and outcome patterns of patients with ACDRs in Iran. This cross-sectional study on ACDRs was conducted among hospitalized patients in a referral university hospital in the city of Isfahan, Iran. The patients' demographics, clinical information, and outcomes, including age, gender, past medical history, medication history, drug reaction with eosinophilia and systemic symptoms (DRESS) diagnosis, Steven-Johnson Syndrome (SJS) diagnosis, toxic epidermal necrosis (TEN) diagnosis, treatment regimen (steroids or intravenous immunoglobulin [IVIG]) and outcome information, including intensive care requirements, severe medical complications, or death, were obtained from medical records. A total of 195 patients with a mean age of 40 years and consisting of 61% females were included. Carbamazepine, lamotrigine, sodium valproate, and phenytoin are the most commonly reported medications. Rate of complications was 45% with DRESS, SJS, and TEN diagnosed in 26%, 47%, and 19%, respectively. Treatment was carried out with steroids and IVIG in 81% and 19%, respectively. Among patients, 15% required intensive care and 5% died. Diagnosis of TEN, older age, and baseline heart disease were predictors of mortality. Patients with SJS were younger and more likely to be males, and they were more likely to have eye complications. On the other hand, patients with the diagnosis of TEN were more likely to receive IVIG and intensive care, and had a higher mortality rate. Our study provides insight into the demographics and clinical patterns of Iranian patients with ACDRs. This will help in predicting rates of complications, treatments, and outcomes in patients and therefore make proper management decisions.

Serum Levels of Interleukin-1 Beta are Decreased in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at the Time of Hospitalization

BACKGROUND: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Some immunological and genetic factors are believed to be involved in the pathogenesis of the disease, including tumor necrotic factor-alpha, interferon-gamma, and interleukin (IL)-17. IL-1β is one of the most prominent cytokines associated with the innate immune response. AIMS: The study aimed to evaluate the serum level of IL-1β in SJS/TEN and the relation between it and the progress of SJS/TEN. METHODS: This was a cross-sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. 48 SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. IL-1β levels were measured using the fluorescence covalent microbead immunosorbent assay (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U test was used to compare serum IL-1β levels. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p < 0.05. RESULTS: 19 SJS patients (39.5%) and 29 TEN patients (60.5%) participated in our study. The mean age was 49.3 years; the range was 19–77 years (47.9% males; 52.1% females). The most common causative drugs were traditional medicine (29.1%), carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of IL-1β of the SJS/TEN group was 26.4 ± 81.7 pg/mL, ranging from 0.5 pg/mL to 447 pg/mL. This level was significantly lower than that of the HCs group (p < 0.001) but not lower than that of the EM group. The mean serum level of IL-1β in the SJS/TEN patients on the day of hospitalization was 26.4 ± 81.7 pg/ml, higher than that on the day of re-epithelialization (1.9 ± 5.6 pg/mL) and the difference was statistically significant with p < 0.01. CONCLUSION: Serum IL-1β level in SJS/TEN patients is lower than in HCs. It is not a good biomarker to differentiate SJS/TEN from EM.

Severe cutaneous adverse drug reactions: incidence, clinical characteristics, treatment, and outcome in pediatric patients.

Severe cutaneous adverse drug reactions (SCARs) can cause significant morbidity and mortality. Clinical data regarding such conditions is still limited in the pediatric population. To investigate the incidence, clinical characteristics, treatment, and outcome of SCARs in Thai pediatric patients. This retrospective study enrolled 52 patients aged less than 18 years who were diagnosed with acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN overlap during January 2005 to August 2021 at Siriraj Hospital. SCARs were slightly more prevalent in females than in males (51.9% vs. 48.1%). Median age at diagnosis was 97 months, and median length of hospital stay was 11 days. DRESS, SJS, TEN, AGEP, and SJS/TEN overlap was found in 44.2%, 36.5%, 9.6%, 5.8%, and 3.8%, respectively. The most common etiologies were antimicrobial agents (40.3%) and anticonvulsants (35.5%). Target lesions, vesicobullous lesions, purpura, positive Nikolsky's sign, and skin tenderness were significant in blistering SCARs. Hematologic (84.6%) and hepatic (65.5%) manifestations were common. Treatment varied according to the clinical features of each condition. Systemic corticosteroids showed some benefit in SJS/TEN. One patient diagnosed with TEN died for an overall SCARs mortality rate of 1.9%. The unique characteristics of SCARs described herein can lead to timely and accurate diagnosis and proper management.

Clinico-Epidemiological Profile and Treatment Outcome of Severe Cutaneous Adverse Drug Reactions in the Paediatric Age Group of 0 to 18 Years: A Retrospective Cohort Study from Southern India

Introduction: The paediatric population is prone to developing cutaneous adverse drug reactions. However, the incidence of Severe Cutaneous Adverse Drug Reactions (SCAR) is rare in this age group, with few studies describing such reactions in detail. Aim: To describe the clinico-epidemiological factors, drug profile, laboratory parameters, and treatment outcomes of SCAR in children admitted to a tertiary care centre in South India. Materials and Methods: A retrospective cohort study was carried out over a 10-year period, including paediatric patients (0-18 years) admitted to Dermatology, Medicine, and Paediatric wards in the tertiary care centre. Demographic details, suspected drugs, comorbidities, personal and family history of drug reactions, physical examination, laboratory parameters, treatment received along with its duration, and the state of morbidity and mortality were recorded. SPSS version 18.0 was used for analysis. Descriptive statistics were used to summarise the demographics and clinical characteristics of the patients. Results: Among all the patients admitted with SCAR, 27 (15%) belonged to the paediatric age group. The median age was 15 years, and the female-to-male ratio was 1.25. Nineteen (70.3%) were diagnosed with Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), and eight (29.6%) were diagnosed with Drug Reaction with Eosinophilia and Systemic Symptom (DRESS). There were no cases of Acute Generalised Exanthematous Pustulosis (AGEP). The most common class of drugs implicated was antiepileptics (62.8%). Two patients (7%) had a family history of drug reactions. All patients had mucosal involvement. The majority of the children responded to intravenous steroids, and two required additional intravenous immunoglobulin injections for clinical improvement. All cases were cured with no mortality or long-term sequelae. Conclusion: The incidence of SCAR in the paediatric age group is significant. Anticonvulsants, particularly phenytoin, carbamazepine, and lamotrigine, need to be used with caution in this age group. Prompt diagnosis and treatment with systemic steroids can reduce mortality, morbidity, and long-term sequelae.

A Clinico-Epidemiological Study of Cutaneous Adverse Drug Reactions in a Tertiary Care Centre of Eastern India.

Adverse drug reactions (ADRs) are major problems in the drug therapy. Cutaneous adverse drug reactions (CADRs) are the most common ADRs. The pattern of CADRs differs among various drugs. To record various morphological patterns of CADRs and their causal relationships among patients attending in a tertiary care centre. An observational, cross-sectional, clinical study was conducted for a duration of one and a half years in a tertiary care centre in eastern India. Patients presenting with suspected CADRs were included if drug identity could be ascertained. Clinical profiling and drug history were recorded, and causality assessment was carried out as per the Naranjo scale. The commonest CADR in our study was fixed drug eruption (FDE) 48.61%, followed by SJS-TEN spectrum 16.66%, maculopapular rash 11.11% and so on. Severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN, SJS-TEN Overlap, AGEP and DRESS accounted for 18 cases (25%). The most common culprit drugs were antimicrobials (54.16%), followed by nonsteroidal anti-inflammatory drugs (15.27%) and anticonvulsants (12.5%). Most of the CADRs were in probable category. The pattern of CADRs and the drugs causing them in our study population are similar to some previous studies but somewhat different from most of the previous Indian studies. The incidence of SCARs was significantly higher than in previous other studies in India and abroad.

Clinical Profiles of Japanese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Collected by a Nationwide System from 2006 to 2023.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening severe cutaneous adverse drug reactions. These diseases are rare, and their onset is difficult to predict because of their idiosyncratic reactivity. The Japan Severe Adverse Reactions Research Group, led by the National Institute of Health Sciences, has operated a nationwide to collect clinical information and genomic samples from patients with SJS/TEN since 2006. This study evaluated the associations of clinical symptoms with sequelae and specific causative drugs/drug groups in Japanese patients with SJS/TEN to identify clinical clues for SJS/TEN treatment and prognosis. Acetaminophen, antibiotics, and carbocisteine were linked to high frequencies of severe ocular symptoms and ocular sequelae (p < 0.05). For erythema and erosion areas, antipyretic analgesics had higher rates of skin symptom affecting <10% of the skin than the other drugs, suggesting narrower lesions (p < 0.004). Hepatic dysfunction, was common in both SJS and TEN, and antiepileptic drugs carried higher risks of hepatic dysfunction than the other drug groups (p = 0.0032). This study revealed that the clinical manifestations of SJS/TEN vary according to the causative drugs.

Approach for delabeling beta-lactam allergy in children.

A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.

Case series of a varied spectrum of drug reactions

Adverse drug reactions are an important cause of iatrogenic morbidity and mortality in the medical field across the globe. As newer drugs emerge into the market, newer adverse reactions are being reported. More than half of these new drugs have serious side effects. A distinction between numerous patterns of drug-induced reactions is potentially of critical importance because a delay even of several hours may make the difference between survival and death. Herein, we report five cases of severe cutaneous adverse drug reactions admitted at our dermatology ward. Key words: Adverse drug reaction, Iatrogenic morbidity

Analysis of circRNA profiles and clinical value in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are challenging to be early diagnosed and evaluate their prognoses. This investigation aimed to analyse the expression profiles of SJS/TEN in peripheral blood mononuclear cells (PBMC) and assess the correlation between circular RNA (circRNA) and disease severity. Sixteen SJS/TEN patients and sixteen controls were enrolled and serum samples of both groups were obtained. CircRNA expression profiles in three SJS/TEN patients and three controls were detected by RNA sequencing and bioinformatic analyses were then performed. The differentially expressed circRNAs were verified by quantitative polymerase chain reaction (qPCR). Then, analysing the correlation of circRNAs with the toxic epidermal necrolysis-specific severity of illness score (SCORTEN) and the epidermal detachment area. A total of 134 circRNAs were differentially expressed in the PBMCs of SJS/TEN individuals, according to our results. The qPCR showed that three circRNAs (hsa_circ_0000711, hsa_circ_0083619 and hsa_circ_0005615) were down-regulated, and one circRNA (hsa_circ_0003028) was up-regulated, which were compatible with the sequencing findings. The concentration of hsa_circ_0083619 was closely associated with the SCORTEN scale (r = -0.581, p = 0.037) and the epidermal detachment area (r = -0.576, p = 0.039). The circRNA-miRNA-mRNA prediction network was used to construct the hsa_circ_0083619/miR-18a-5p/BCL2L10 axis. The hsa_circ_0083619 could serve as a disease severity indicator for SJS/TEN. Through bioinformatics analysis, we speculated that hsa_circ_0083619/miR-18a-5p/BCL2L10 axis might play a role in SJS/TEN pathogenesis.

Cutaneous Adverse Drug Reactions to Antibiotics: How Much is the Extent of the Problem?

Medication-related harm or adverse drug reaction is a great global health concern today. They are frequent and, most often, devastating. With the rising incidences of drug-related adverse outcomes, it is imperative that clinicians have the knowledge and understanding of these occurrences to prevent, diagnose, and manage them properly. Skin is a very commonly affected organ system, and incidences of cutaneous adverse drug reactions are between 1-5% depending on the geographic location. Up to 60% or more of all adverse drug reactions may represent cutaneous reactions. These may fall into either of the dose-dependent or dose-independent categories. Being the most prescribed and utilized drug group, antibiotics have been implicated as one of the major drug groups causing cutaneous drug reactions. There is ample evidence that antibiotics cause severe and non-severe cutaneous adverse drug reactions. A review of the present literature was done using MEDLINE/PubMed, Google Scholar, and other search engines to gather evidence to find how extensive the problem is and how much the burden is. Which will enlighten clinicians from all backgrounds and medical students and help them deal with cutaneous adverse drug reactions more prudently

LB1799 Single-cell type proteomic analysis in FFPE tissue sections of severe cutaneous adverse drug reactions

LB1799 Single-cell type proteomic analysis in FFPE tissue sections of severe cutaneous adverse drug reactions