Cutaneous Adverse Reactions Research Articles

Cutaneous Adverse Drug Reactions - B

Cutaneous Adverse Drug Reactions - B

A Case Report of Gamiseungmagalgeun-tang for a Cutaneous Adverse Drug Reaction in a Patient with Intracerebral Hemorrhage

A cutaneous adverse drug reaction (CADR) refers to an unexpected skin and mucosal reaction caused by drug administration. In the present case, a 65-year-old male presented with generalized itching and a maculopapular rash after taking Western medication, including anticonvulsants and a nonsteroidal anti-inflammatory drug (NSAID). He was treated with Gamiseungmagalgeun-tang, a traditional Korean herbal medicine. After treatment, the patient’s symptoms improved, without recurrence. Based on this experience, traditional Korean herbal medicine, including Gamiseungmagalgeun-tang, may be beneficial for improving symptoms of CADRs.

Chinese expert consensus on diagnosis and treatment of immune checkpoint inhibitor-related skin adverse reactions (2024 edition)

Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the 'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.

The association between HLA-B variants and amoxicillin-induced severe cutaneous adverse reactions in Chinese han population.

Amoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs. Four patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins. Compared with AMX-tolerant controls, a significant association of HLA-B*15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68-1275.67; p = 7.34 × 10-3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10-4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis. Our findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMX-induced SCAR still needs to be further explored in larger cohort studies and other ethnic populations.

Rare cutaneous adverse reactions associated with GLP-1 agonists: a review of the published literature.

Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians.

Symmetrical drug-related intertriginous and flexural exanthema with high-risk systemic features: a unique clinical phenotype in hospitalized patients.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is classically considered a low-risk, self-limiting eruption lacking systemic manifestations and sparing facial and mucosal areas. We present 7 inpatients meeting diagnostic criteria for SDRIFE with concomitant systemic manifestations ± high-risk facial involvement acutely after antibiotic exposure (mean latency 6.71days). These cases deviate from classic, self-limited SDRIFE and represent a unique phenotype of SDRIFE, characterized by coexisting extracutaneous manifestations. Onset of systemic stigmata coincided with or preceded cutaneous involvement in 4 and 3 patients, respectively. All patients developed peripheral eosinophilia and 6 patients had ≥ 2 extracutaneous systems involved. Facial involvement, a high-risk feature associated with severe cutaneous adverse reactions but atypical in classic SDRIFE, occurred in 4 cases. Patients had favorable clinical outcomes following drug cessation and treatment with 4-6week corticosteroid tapers. We suggest that baseline labs be considered in hospitalized patients with antibiotic-induced SDRIFE. These patients may also necessitate systemic therapy given extracutaneous involvement, deviating from standard SDRIFE treatment with drug cessation alone.

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.

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

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.

Fixed drug eruption secondary to etoricoxib

Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.

Improving Clinical Practice Through Patient Registries in Allergy and Immunology

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity (IEI), food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in IEI, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

A study of cutaneous adverse drug reactions in the dermatology department of a tertiary care teaching hospital in Gujarat

Background: Various drugs are responsible for different cutaneous adverse drug reactions (CADRs). Considering variation in drug responses and the day-to-day increasing burden of ADRs, this study was done with emphasis on the need for effective evaluation and the reporting of the ADR reporting programme. Methods: This was an observational cross-sectional study conducted for the duration of six months in the dermatology department to evaluate various clinical patterns of CADRs. Results: A total of 60 CADRs were reported. Among them, 51.67% were present in males and 48.33% were present in females. The most common CADR was FDE (35%), followed by macula-papular rash (25%). Antimicrobials were most commonly responsible for CADRs, followed by NSAIDs, antiepileptic, anti-gout, and anti-hypertensive medications. Conclusions: For better patient care, drug safety, and rational use of medicines, knowledge of various drugs responsible for CADRs can be useful for health care professionals to reduce mortality and morbidity by monitoring, reporting, and assessment of CADRs whenever detected.

Drug induced bullous fixed drug eruption: a case report

Bullous fixed drug eruption, which is a cutaneous adverse drug reaction, is commonly seen with antimicrobials and analgesics. Bullous drug eruptions are infrequent, but because they pose a challenge both to affected patients and to treating physicians, they are considered to be the most severe cutaneous adverse reactions (SCAR). It is important to recognize these conditions and to differentiate them from other clinical entities involving blister formation. There may be early signs and symptoms that indicate a severe bullous drug eruption even before blisters and erosions of the skin and mucous membranes become obvious. Once the diagnosis is suspected, appropriate diagnostic procedures and adequate management must be initiated. The latter includes identification of the potentially inducing drug, although it should be taken into account that not all cases of bullous eruptions are drug-induced. In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately. In addition to best supportive care, immunomodulating therapy may be considered. Here we report 64-year-old male with bullous fixed drug eruptions due to doxycycline administration.

Clinical features of drug reaction with eosinophilia and systemic symptoms: A retrospective study in a reference centre of dermatology in Madagascar

AbstractBackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is drug‐induced hypersensitivity reaction that can have fatal complications. Three sets of diagnostic criteria have been proposed, however, consensus is lacking.ObjectivesThis study aimed to describe the causative agents, severity, and the clinical course of patients with DRESS in Antananarivo, Madagascar.MethodsA cross‐sectional study was conducted in patients seen for DRESS, in the department of dermatology at the University Hospital Antananarivo, Madagascar from 2014 to 2022. European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria was used for the diagnosis. Demographic data, latency periods, clinical and laboratory findings, culprit drugs, and outcomes were assessed.ResultsA total of 24 patients were included. Fifteen patients were female. The three most common culprit drugs were carbamazepine (17 patients), phenobarbital (2 patients), and ampicilline (2 patients). Median onset time (interquartile range) was 20 days (range: 7–62 days). Skin rash was present in all patients, and fever in 18 patients. A total of 12 patients showed two or more internal organs involved. Liver and kidney injuries were the most common visceral manifestation. All patients had eosinophilia. Fifteen patients received systemic corticosteroids. Two mortality cases were reported due to DRESS‐related fulminant liver failure and to nosocomial respiratory infection. Mortality was associated with higher eosinophilia (p = 0.03), higher creatininemia (p = 0.04), and shorter time of latency (p = 0.04).ConclusionsOur study show that DRESS is associated with severe morbidity. Early detection and withdrawal of the culprit dru gis crucial to save life and reduce morbidity.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions.

Eruptions in focus: cefadroxil and the uncommon realm of fixed-drug reactions: a case report

This case report explores a rare case of localized fixed-drug eruption (FDE) induced by cefadroxil, a first-generation cephalosporin. FDE, characterized by recurrent lichenoid lesions at specific sites upon drug exposure, is an immunological cutaneous adverse reaction. The incidence of FDE due to cephalosporins is infrequently reported, making this case noteworthy. We present a 51-year-old male who developed brownish-black patches and painful blisters on his extremities after initiating treatment with Cefadroxil for a minor toe injury. The patient's symptoms, clinical course, and subsequent recovery are detailed. Treatment involved corticosteroids, antibiotics, and topical agents. The report also provides immunological insights into FDE pathogenesis, involving CD8+ memory T cells, cytokine production, and the role of CD4+ regulatory T cells. While the exact pathogenesis of FDE remains elusive, this report sheds light on the mechanisms contributing to the self-limited nature of these eruptions. Causality assessment using the Naranjo algorithm categorized the association between cefadroxil and FDE as probable. This case report contributes to the limited literature on FDE caused by cephalosporins and underscores the importance of recognizing and managing such dermatological reactions. The broader implications of understanding FDE pathogenesis and the rarity of cephalosporin-induced cases provides valuable insights for clinicians and researchers.

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.

Cutaneous adverse drug reactions in children with a focus on hypersensitivity to systemic drugs: A narrative review

Drug hypersensitivity in children is rare compared to adults. Children more frequently develop an infection-associated exanthema. Nevertheless, about 95% of children with drug hypersensitivity present with mucocutaneous involvement. Early recognition of typical clinical symptoms is important to reduce morbidity and mortality. We review relevant type I and type IV disorders of drug hypersensitivity in children and discuss their differential diagnoses and treatment.

Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients

BackgroundAllopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. Methods: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls.ResultsOut of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2–266.8; P = 1.9 × 10− 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3–670.5 and p-value = 1.7 × 10− 27).ConclusionsThus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.

Ctrl-X, Ctrl-C and Ctrl-V in Veterinary Dermatology: Skin microbiota transplantation as a promising approach for dogs with cutaneous adverse food reactions

The probability of influencing the skin microbiome for addressing skin disorders opens a novel aisle of therapy. This study aimed to evaluate the efficacy of skin microbiota transplantation (sMt) for cutaneous adverse food reactions (caFr) in dogs. Ten client-owned dogs with caFr were included in the study. Unenriched heterologous sMt was performed using Nivea Skin Refining Clear-Up Strips (N-cUs). The bacterial microbiota of skin samples was analysed by next-generation sequencing of the 16S rRNA gene. Other relevant biomarkers were involved in VAS (visual analogue scale of pruritus score), CADESI-04 (canine atopic dermatitis extent and severity index) and epidermal corneometric analysis. Increased Faecalibacterium (0 to 1.9 %), Peptoclostridium (5.49 % to 9.11 %) and Collinsella (0.65 % to 8.91 %), and decreased Fusobacterium (19.16 % to 9.06 %), Porphyromona (8.75 % to 0.13 %), Streptococcus (1.63 % to 0.14 %) and Staphylococcus (1.09 % to 0.49 %) was evidenced before and after sMt, respectively. Treatment with sMt effectively controlled clinical signs and drastically reduced median VAS pruritus (6.5 vs. 2) and CADESI-04 scores (74.50±22.62 to 19.30±11.30) (p<0,001). In addition, skin pH and hydration values were improved (p<0,001) after sMt. The heterologous and unenriched sMt with N-cUs could be responsible for the clinical recovery observed in this study.