Drug Eruption Research Articles

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 In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately.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.

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.

Fixed Drug Eruption due to Dupilumab.

Fixed Drug Eruption due to Dupilumab.

Trips Through the Skin: Reviewing Cutaneous Drug Reactions to Psychedelics and Hallucinogens.

Although psychedelic and hallucinogenic substances have gained popularity for therapeutic use, their dermatologic adverse effects are poorly characterized. This review characterizes the cutaneous reactions associated with psychedelic and hallucinogenic drugs. A review of PubMed and Scopus was conducted from the inception of databases to August 31, 2023. Search terms included drug names and classes (cannabis, MDMA, ecstasy, 3,4-methylenedioxymethamphetamine, psychedelics, hallucinogens, peyote, marijuana, lysergic acid diethylamide, LSD, ketamine, dimethyltryptamine, DMT, phencyclidine, PCP, dextromethorphan, psilocybin, and ayahuasca), and dermatosis terms (dermatitis, contact dermatitis, drug eruption, skin reaction, and urticaria). Studies were included if there was an association with a psychedelic or hallucinogenic and any cutaneous reaction; studies without both components were excluded. Twenty-two studies met inclusion criteria, describing reactions to cannabis (10 studies), MDMA (5 studies), ketamine (4 studies), and psilocybin (3 studies). Forty total patients were included. Among cannabis-related reactions, the most common reaction was type I hypersensitivity by topical exposure (n = 21). Three patients reported type IV hypersensitivity reactions to contact with cannabis or cannabis-derived oils, all of whom experienced vesicular contact dermatitis. Two additional patients presented with an erythema-multiforme-like reaction and acute generalized exanthematous pustulosis after systemic administration, respectively. MDMA was associated with acneiform eruptions (2 cases), an urticarial eruption, a guttate psoriasis-like reaction, a fixed drug eruption, and Stevens-Johnson syndrome (1 case). Four patients reported type I hypersensitivity reactions to ketamine. Four patients reported vesicular eruptions, cyanosis, or widespread jaundice to psilocybin. Of the cases, 8 patients had cutaneous reactions that resolved with drug cessation, 10 resolved with cessation plus treatment, and resolution in 7 cases was not reported. Zero studies were found describing other psychedelic or hallucinogenic compounds. Further research is required to characterize reactions and treatments linked to the variety of extant psychedelics and hallucinogens.

Drug Eruption After Subcutaneous Ofatumumab Exposure in Two Patients with Relapsing Multiple Sclerosis (P2-6.009)

Drug Eruption After Subcutaneous Ofatumumab Exposure in Two Patients with Relapsing Multiple Sclerosis (P2-6.009)

Fixed Drug Eruption to Levocetirizine Detected by Patch Testing.

Fixed Drug Eruption to Levocetirizine Detected by Patch Testing.

The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients.

Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir.

Specific human leukocyte antigen (HLA) polymorphisms combined with certain drug administration strongly correlate with skin eruption. Abacavir hypersensitivity (AHS), which is strongly associated with HLA-B*57:01, is one of the most representative examples. Conventionally, HLA transmits immunological signals via interactions with T cell receptors on the cell surface. This study focused on HLA-mediated intracellular reactions in keratinocytes that might determine the onset of skin immunotoxicity by drug treatments. Abacavir exposure resulted in keratinocytes expressing HLA-B*57:01 exhibiting endoplasmic reticulum (ER) stress responses, such as immediate calcium release into the cytosol and enhanced HSP70 expression. In contrast, keratinocytes expressing HLA-B*57:03 (closely related to HLA-B*57:01) did not show these changes. This indicated that HLA-B*57:01 has a specific intracellular response to abacavir in keratinocytes in the absence of lymphocytes. Furthermore, abacavir exposure in HLA-B*57:01-expressing keratinocytes elevated the expression of cytokines/chemokines such as interferon-γ, interleukin-1β, and CCL27, and induced T lymphoblast migration. These effects were suppressed by ER stress relief using 4-phenylbutyrate (4-PB). HLA-B*57:01-transgenic mice also exhibited ER stress in epidermal areas following abacavir administration, and abacavir-induced skin toxicity was attenuated by the administration of 4-PB. Moreover, abacavir bound to HLA-B*57:01 within cells and its exposure led to HLA-B*57:01 protein aggregation and interaction with molecular chaperones in the ER of keratinocytes. Our results underscore the importance of HLA-mediated intracellular stress responses in understanding the onset of HLA-B*57:01-mediated AHS. We provide the possibility that the intracellular behavior of HLA is crucial for determining the onset of drug eruptions.

Pityriasiform drug eruption associated with venetoclax for acute myeloid leukaemia.

Venetoclax is a targeted antileukaemic therapy that has emerged as the primary treatment of acute myeloid leukaemia in patients of advanced age or who would otherwise be ineligible for standard chemotherapy. Despite the documented evidence of cutaneous side effects of venetoclax, few reports have clarified presenting cutaneous features beyond the descriptors 'rash' and 'pruritus'. In this report, we describe the development of a pityriasiform drug eruption following venetoclax-based induction therapy for acute myeloid leukaemia. This study provides further evidence to characterise the range of cutaneous adverse events that are associated with venetoclax-based therapy. Further studies are needed to elucidate the epidemiology and pathophysiology of venetoclax-induced cutaneous toxicities.

The Evaluation of Dermatological Disease Profiles of Neurosurgery Inpatients: A Tertiary Clinic Experience.

Both the skin and neuronal systems originate from the ectoderm. In patients hospitalized for neurosurgery, their skin may be affected by genetic and environmental factors. This study researched disease relationships by evaluating the profile of hospitalized neurosurgery patients who consulted with dermatologyin a tertiary clinic (Neurosurgery Clinic, Ankara Training and Research Hospital, Ankara). This study included hospitalized neurosurgery patients who consulted with dermatology. Age, gender, type of hospitalization, neurosurgical diseases, and dermatology diseases were selected as study variables. The medical health records of the patients were retrospectively scanned and analyzed. A total of 172 consultations were analyzed. The mean age of patients was 44.7 years oldranging from 1 year to99 years old. The percentage of male patients was 54.7%; 25.5% of the patients were hospitalized for cerebral vascular diseases, 30.2% for spinal diseases, 22.1% for tumors, 12.2% for infections, and 1.2% for other neurosurgical diseases. The most commonly diagnosed dermatological disease in patients was drug eruptions (18.6%), followed by seborrheic dermatitis (16.2%) and contact dermatitis (14.5%). According to this study, the most commonly diagnosed dermatological diseases in neurosurgery inpatients were drug eruption, contact dermatitis, and seborrheic dermatitis. The results of this study may be helpful in terms of neurosurgical training planning and treatment management.

Most Common Drug Eruptions by Pattern and Drug Class: A Review

Cutaneous drug reactions come in many different morphologies, distributions and severities ranging from pruritus and erythema to diffuse epidermal denudation requiring hospitalization. The wide variety of presentations and medications responsible make identification and elimination of the offending agent difficult. Here these authors present a review of the common morphologic drug eruptions and their offending drugs.

Case Report: Ofloxacin-induced fixed drug eruption

Background Fixed Drug Eruption (FDE) is a rare form of drug-induced dermatoses that appears as well-defined, erythematous patches occurring within hours of medication’s administration with or without blistering and resolves with post-inflammatory residual hyperpigmentation. Case presentation A 50-year-old male patient visited the outpatient department with chief complaints of burning micturition, increased urine frequency, and high-grade fever with chills lasting three days. Blood and urine investigations indicated leukocytosis and remnants of pus cells, respectively, confirming the diagnosis of urinary tract infection intervened with a tablet ofloxacin. Two hours after drug consumption, intense itching was noticed over the body, which soon progressed to blackening discoloration; blisters developed with a burning sensation over the webs of the palm and on the arm, with hyperpigmentation of the lower lip. Furthermore, painful patches with serous discharge developed in the oral cavity and penile tip. He had encountered a similar episode seven years before, which confirmed the diagnosis of fixed drug eruption (FDE). Immediate treatment included injectable steroids, antihistamines, cephalosporin antibiotics, and intravenous fluids with discontinuation of the ofloxacin drug. He adhered well to the treatment and had a remarkable improvement after 72 hours with residual hyperpigmentation, following which, the patient was advised to avoid similar medicine in the future to prevent a recurrence. Conclusions This case report concludes that the adverse drug reactions should be considered mandatorily with antibiotic audits on a regular basis to ensure that the course of treatment is appropriate and adequate, and any inappropriate reaction should be reported immediately. The rationality of the treatment and inappropriate prescriptions must be reported.

Nimesulide-Induced Fixed Drug Eruption Followed by Etoricoxib-Induced Fixed Drug Eruption: An Unusual Case Report and Review of the Literature.

Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care.

Clinical Profile of Patients with Lichenoid Drug Eruption: A Observational Study.

Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated. To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved. In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature. A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were "definite," whereas two-thirds were designated as "probable." LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.

Pharmacokinetic Simulation Study: Exploring the Impact of Clinical Parameters on Lamotrigine for Different Patient Populations with Implications for Liver Function Assessment and Therapeutic Drug Monitoring

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug’s clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine’s DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine’s pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions.

Drug rash with eosinophilia and systemic symptoms to anti-tuberculosis therapy: A retrospective review of inpatients at an academic medical centre in the United States.

This retrospective cohort study analyzes the presentation, diagnosis, and treatment outcomes of patients who developed drug rash with eosinophilia and systemic symptoms (DRESS) to tuberculosis (TB) therapy in a TB non-endemic region. Anti-TB agents represented 7.5% of all antimicrobial-induced DRESS cases, and rifampin was the most commonly implicated agent among drugs used to treat TB.

Adverse events of biological agents in pediatric rheumatologic diseases

ABSTRACT Objectives To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs). Methods This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records. Results Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54–0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold (p = 0.024, 95% CI: 1.26–27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient. Conclusion The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

Fixed Drug Eruptions Due To/Caused by Levocetirizine and Cetirizine: An Uncommon Adverse Cutaneous Drug Reaction to Commonly Used Piperazine Derivatives.

Fixed Drug Eruptions Due To/Caused by Levocetirizine and Cetirizine: An Uncommon Adverse Cutaneous Drug Reaction to Commonly Used Piperazine Derivatives.

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review.

Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.

Retrospective Analysis of Inpatient Dermatologic Consultations in a Residency Training Program

Objective: This study assessed the prevalence and clinical characteristics of inpatient dermatologic diseases, examined trends over 3 academic years in a tertiary care hospital in Thailand, and evaluated their relevance to the current dermatology residency curriculum. Materials and Methods: A retrospective review was performed at the Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Consultation records from July 2018 to June 2021 were assessed. Data extracted included patient age, sex, referring departments, and diagnoses. Results: Of the 1964 consultations, 2002 diagnoses were identified. Consistent with previous findings, the predominant diagnostic categories were drug eruptions (28.02%; 561), eczema (16.18%; 324), and viral infections (9.29%; 186). Internal medicine made the most requests, followed by surgery and orthopedics. While the prevalence of consulted diseases remained constant over the 3 academic years, the total number of consultations increased. Most of the consulted conditions were already covered in the “must-know” section of the dermatology residency curriculum, with a few exceptions. The consultation cases satisfied the inpatient evaluation requirements of EntrustableProfessional Activity. Conclusion: The prevalence of inpatient dermatologic diseases was highest for drug eruptions, followed by eczema and viral infections. The consistent trend in the prevalence of these consulted diseases underscores the significance of inpatient dermatology. Incorporating these insights into revisions of the dermatology residency curriculum may enhance the training of dermatologists.