Cutaneous Adverse Reactions Research Articles

Rheumatic Immune-Related Adverse Events With Anti-cyclic Citrullinated Peptide Positivity and Cutaneous Adverse Drug Reactions: A Case Report

Rheumatic Immune-Related Adverse Events With Anti-cyclic Citrullinated Peptide Positivity and Cutaneous Adverse Drug Reactions: A Case Report

Factors Inducing Cutaneous Adverse Reactions in Cancer Patients Treated with PD-1 and PD-L1 Inhibitors: A Machine-Learning Algorithm Approach

Immune checkpoint inhibitors (ICIs) show promise in cancer treatment but can lead to immune-related adverse events (irAEs), notably affecting the skin. Understanding the factors behind these skin reactions is crucial for effective management during treatment. Hence, the aim of this study was to uncover associations between patient characteristics and cutaneous adverse reactions among cancer patients undergoing ICI treatment. The study involved 209 cancer patients receiving ICIs. Statistical methods, including the chi-square test, Fisher's exact test, and multivariable logistic regression, were employed to analyze variables such as hypertension, antihistamine use, cancer metastasis, diabetes, and opioid usage. Additionally, machine learning techniques, including logistic regression, elastic net, random forest, and support vector machines (SVM), were utilized to develop predictive models anticipating skin-related adverse events. Results highlighted significant associations between specific patient attributes and the incidence of skin reactions post-ICI treatment. Notably, patients using antihistamines or with cancer metastasis exhibited higher rates of skin adverse reactions, while those with diabetes or using opioids displayed lower incidence rates. Robust performance in forecasting these adverse events was observed, particularly in the predictive models employing logistic regression and elastic net. This pioneering study contributes crucial insights into predictive modeling for ICI-induced skin reactions, emphasizing the importance of personalized treatment strategies. By identifying risk factors and utilizing tailored predictive models, healthcare providers can proactively manage adverse events, optimizing the benefits of ICIs while mitigating potential side effects.

Feedback regulation of VISTA and Treg by TNF-α controls T cell responses in drug allergy.

Severe cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life-threatening conditions with a mortality of 4%-20%. The clinical application of tumor necrosis factor-alpha (TNF-α) antagonist improves the outcome of some SCARs patients; however, this is complicated by the elusive and varied immunopathogenesis. To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab. To clarify the precise process and optimize the therapy regimen of SCARs, we performed single-cell sequencing, invitro functional and clinical analysis of patients with SCARs. We observed that TNF-α breaks drug-specific T-cell tolerance by inhibiting the expression of V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA). Furthermore, TNF-α generated a positive feedback loop in the early phase of drug-specific T-cell activation, whereby B cells acted reciprocally on the corresponding T cells to reinforce TNF-α cytokine expression. In contrast, this pathway of TNF-α-VISTA signaling did not operate in memory effector T cells. Drug-specific memory effector T-cell responses were inhibited by increasing Treg cell expression in a negative feedback loop, with TNF-α antagonists preventing the inhibitory effect. These observations align with the clinical analysis that early but not late intervention with TNF-α antagonists significantly improved outcomes in SCARs patients. Our findings defining feedback regulation of VISTA and Treg cells by TNF-α in different stages of the drug-specific T-cell response and, indicate that a Treg agonists, instead of TNF-α antagonists, could be used for treatment of patients with progressive SCARs.

EVALUATION OF CUTANEOUS ADVERSE DRUG REACTIONS IN A TERTIARY CARE HOSPITAL IN SOUTHERN INDIA: A RETROSPECTIVE ANALYSIS

Objective: This study was undertaken to understand the demographic profile, common causative drugs, and the presentations of cutaneous adverse drug reactions (CADR) among the patients of our hospital. Methods: This is a retrospective analytical study. All CADR reported to our adverse drug reaction monitoring center from dermatology outpatient department (OPD), other OPDs, intensive care units, and inpatient wards of our hospital from September 2022 to March 2024 was collected from VIGIFLOW (software used by the pharmacovigilance program of India). The data was then analyzed. Results: A total of 272 CADR were reported over the study period. The median age of presentation was 41 years (Interquartile range=23). Overall 44 (16.18%) serious and 228 (83.82%) non-serious CADR were reported. Erythematous maculopapular rash was the most common clinical presentation (63%). Bullous exfoliative drug eruptions and Stevens Johnson’s syndrome were some of the serious CADR. The most common suspected medications were antibiotics (42.15%) followed by non-steroidal anti-inflammatory drugs (8.92%). In 76% of the cases, the suspected medication was withdrawn. The outcome was reported as “Recovering” in 52% of the cases. On causality assessment, 251 (92%) CADR were classified as “Possible.” Conclusion: A CADR is a common yet preventable health problem. As seen from our study, most of the suspected medications were withdrawn and subsequently the patients were recovering from the CADR. Hence, early diagnosis, identification, and withdrawal of the implicating drugs help in timely recovery and prevention of complications, which in turn help in decreasing the burden on our healthcare system.

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.

Dysregulation of Regulatory T Cells and Autoimmune Sequelae in DRESS: Insights From Flow Cytometry and NanoString Analysis.

Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4+CD25+CD127-FoxP3+ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA-4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL-10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co-culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients.

Oral Antibiotics Associated with Increased Risk of Serious Cutaneous Adverse Drug Reactions.

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Adverse reactions to trimethoprim/sulfamethoxazole for melioidosis eradication therapy: an evaluation of frequency and risk factors

Trimethoprim/sulfamethoxazole is the first-line agent for oral eradication therapy for melioidosis but has been associated with toxicity in this context. This study aimed to quantify adverse drug reactions (ADRs) to trimethoprim/sulfamethoxazole when used for treatment of melioidosis, and assess risk factors for ADR development.A retrospective review of antimicrobial associated ADRs was performed in all patients treated for melioidosis in the Northern Territory of Australia from January 2017 – September 2022.Over this time, 268 treatment episodes from 256 individuals were included. The frequency of clinician-attributed ADRs to trimethoprim/sulfamethoxazole (51% of exposed) was higher than for other antimicrobials used (ceftazidime 12%, meropenem 8% and doxycycline 12% of those exposed; p<0.0001). 44% of those treated with trimethoprim/sulfamethoxazole required drug cessation or dose reduction and 5 individuals (2%) had a severe cutaneous adverse reaction, with one fatality. Acute kidney injury was the most frequent ADR (25% of those exposed), with age and pre-existing renal disease independently associated with its development.Here we report very high rates of ADRs attributed to trimethoprim/sulfamethoxazole resulting in frequent discontinuation of this drug as part of oral eradication therapy for melioidosis. Further work is needed to balance the necessity and toxicity of this drug in this clinical context.

COVID-19 and severe cutaneous allergic reactions to sulfonamides.

Background: Sulfonamides are associated with severe cutaneous adverse reactions (SCARs). Coronavirus disease 2019 (COVID-19) triggers an immune response, which may increase the likelihood of developing a hypersensitivity reaction. Objectives: We sought to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the probability of developing SCARs and/or erythema multiforme (EM) reactions to sulfonamides. Methods: In the propensity score-matched cohort study by using the de-identified TriNetX Research data base, patients who had an exposure to antibiotic or non-antibiotic sulfonamides between March 1, 2020, and January 1, 2023, were divided into two groups based on the presence or absence of a previous COVID-19 infection within 6 months of starting the sulfonamide agent. The outcomes studied were the 30-day risk of developing SCARs or EM (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, or EM) within 3 months of sulfonamide exposure. Cohorts were matched based on baseline demographics; malignant lymphoid neoplasms; human immunodeficiency virus; systemic lupus erythematosus; bone marrow transplantation; diabetes; psoriasis; seizures; gout; solid organ or stem cell transplantation; COVID-19 vaccination; and exposure to risk medications, including allopurinol, levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, phenobarbital, abacavir, nevirapine, piroxicam, tenoxicam, or mexiletine. Results: When comparing 345,119 patients on sulfonamides and with previous COVID-19 to an equal number of sulfonamides users without a previous COVID-19, patients with COVID-19 had a lower risk of developing any form of SCARs (relative risk 0.39 [95% confidence interval, 0.26, 0.58]; p < 0.001). Conclusion: Previous SARS-CoV-2 infection seems to be associated with a lower probability of developing SCARs or EM among patients using sulfonamides.

Web application for assisting non-dermatology physicians in learning and managing patients with common cutaneous adverse drug reactions: a multicenter randomized controlled trial

Background Cutaneous adverse drug reactions (CADRs) remain a challenge for non-dermatologists. Medical-related applications to assist in learning about and managing patients with CADRs are scarce. We aimed to evaluate the efficacy of a web application for non-dermatologists in managing CADRs by comparing the knowledge scores of users and non-users. Materials and Methods A multicenter randomized controlled trial was conducted between January 2023 and May 2023. Clinician participants were randomized (1:1) into the application and control groups using a simple randomization method. Knowledge scores between the groups were compared to evaluate the efficacy of the web application, and participants’ perspectives on the application were also collected. Results A total of 44 clinician participants were included in the final analysis. The median age was 33.0 years (95% confidence interval (CI) 27.5–35.0) and predominantly female (56.8%). The score in the application group (median, 27.0; 95% CI, 25.0–28.0) was significantly higher than that in the control group (median, 14.0; 95% CI 13.0–17.0) (p < 0.001). There were no differences in scores between the sex groups (p = 0.695), between general practitioners (GPs) and non-GPs (p = 0.93), or among groups with different frequencies of evaluation of patients with CADRs (p = 0.266). In addition, the participants in the application group rated a high level of overall satisfaction. Conclusion The web application for CADRs is an effective and convenient tool for assisting non-dermatologist physicians in learning and providing initial management with a high level of satisfaction. However, prospective long-term randomized controlled studies are required to confirm the efficacy of this tool.

Systematic review and meta-analysis of non-SCORTEN predictors of mortality in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe cutaneous adverse reactions that result in in-hospital death in 12-49% of cases. The severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is the most widely used mortality prognosis score; however, it has been shown to have critical limitations. Other mortality predictors not incorporated in SCORTEN or other predictor tools are being increasingly reported. This systematic review and meta-analysis aimed to synthesize and evaluate the predictors of mortality in adults with Stevens-Johnson syndrome and toxic epidermal necrolysis not included in SCORTEN. It was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Potential bias was assessed using the National Institutes of Health (NIH) criteria. Forty articles describing results from 52,398 cases were included. Sixteen predictors were reported in five or more articles, and thirty-three were reported in two to four articles. Meta-analysis showed preexisting renal disease (odds ratio (OR): 3.14, 95% confidence interval (CI): 1.99-4.97, P < 0.0001, I2 = 21%), renal involvement (OR: 5.62, 95% CI: 2.29-13.77, P = 0.0002, I2 = 36%), respiratory involvement (OR: 3.14, 95% CI: 1.25-7.92, P = 0.015, I2 = 66%), diabetes mellitus (OR: 1.87, 95% CI: 1.21-2.89, P = 0.005, I2 = 19%), sepsis (OR: 5.64, 95% CI: 2.81-11.29, P < 0.0001, I2 = 63%), comorbidity (OR: 9.13, 95% CI: 4.60-18.12, P < 0.0001, I2 = 0%), and time to hospitalization (OR: 2.56, 95% CI: 1.15-5.65, P = 0.021, I2 = 93) increased risk of mortality. This systematic review and meta-analysis support several clinical and laboratory parameters not included in SCORTEN (preexisting renal disease, renal involvement, respiratory involvement, diabetes mellitus, sepsis, comorbidities, and time to hospitalization) as predictors of mortality in adults with SJS/TEN. The future utilization of these factors may improve mortality prognostication in adults with SJS/TEN.

Infectious complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta-analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN. This review was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-six articles describing results from 1446 cases were included. Skin infection was the most commonly diagnosed infection. The pooled prevalence of sepsis, respiratory tract infection, skin infection, and urinary tract infection was 27.3%, 21.5%, 37.5%, and 21.8%, respectively. Staphylococcus aureus was the most commonly identified organism. The overall quality of the studies was suboptimal, and the level of heterogeneity was high. The skin, bloodstream, respiratory, and urinary tracts are most commonly infected in the course of adult SJS and TEN. During hospitalization, clinicians should closely monitor and promptly investigate for these as well as several other infectious complications. More research is needed, with greater attention to the risk factors and causative organisms that cause these infections.

Differences in safety profiles of anti-herpesvirus medications: a real-world pharmacovigilance study based on the FAERS database

ABSTRACT Background Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use. Methods We collected data on acyclovir, ganciclovir, valaciclovir, and foscarnet from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2023. Disproportionality analyses were conducted to evaluate the risk of AEs. Results All drugs exhibited significant associations with hematotoxicity, with ganciclovir and foscarnet being more myelosuppressive. The correlation with renal impairment ranked as follows: foscarnet, ganciclovir, valaciclovir, and acyclovir (ROR = 16.72, 7.06, 3.51, and 2.02, respectively). Regarding hepatotoxicity, ganciclovir was associated with acute-on-chronic liver failure (ROR = 52.83), and foscarnet was associated with fulminant hepatitis (ROR = 49.91). In the nervous system, acyclovir showed the highest intensity of neurotoxicity (ROR = 14.95). Valaciclovir ranked first in toxic encephalopathy (ROR = 64.70). Foscarnet showed the highest intensity of status epilepticus (ROR = 6.45). Besides, acyclovir showed the strongest association with severe cutaneous adverse reactions (SCARs). Conclusions Our study revealed differences in safety profiles of four anti-herpesvirus medications. Ganciclovir exhibited the highest risk of hematotoxicity but appeared relatively safe in seizures and SCARs. Foscarnet was more likely to induce nephrotoxicity, seizures, and electrolyte imbalances than others. Acyclovir and valaciclovir were strongly associated with plasmacytosis, neurotoxicity, and SCARs.

Lamotrigine associated extensive hyperpigmentation: A case report and literature review.

Lamotrigine (LTG)-associated extensive hyperpigmentation is rare and may persist for a long time or even become permanent. LTG-associated cutaneous adverse reaction (CAR) manifests initially as mild maculopapular exanthema (MPE). The first step in CAR therapy is to immediately discontinue the offending LTG for predicting evolution to mild or severe forms not always possible. Here, we present a rare case of LTG-associated extensive hyperpigmentation for delaying the withdrawal of LTG. We describe the case of a female adolescent with a history of depression managed with LTG, who developed a mild MPE. Unfortunately, the patient did not discharge LTG after the occurrence of MPE until 20 days later. Then she developed a residual extensive hyperpigmentation in her trunk and extremities. After a series of physical examinations and retracing past medical history, she was diagnosed with LTG-associated extensive hyperpigmentation. The patient refused any treatment. Nine months later, there still existed residual hyperpigmentation in her trunk and extremities, and the range and color of hyperpigmentation have not changed significantly. This case suggests that LTG may cause not only MPE but also extensive hyperpigmentation. When a patient displays a mild MPE following the initiation of LTG in the outpatient clinic, LTG-associated CAR should not be overlooked as a diagnosis, and early withdrawal of LTG should be considered at first.

Implementation of HLA-related genotype-guided prescribing in Singapore.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To describe the implementation of human leukocyte antigen (HLA)-related genotype-guided prescribing in Singapore. Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B*15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B*58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available. HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.

Frequency of cutaneous drug reactions in the outpatient dermatology clinic at the National Institute of Cardiology Ignacio Chávez over a ten-year period

Cutaneous adverse drug reactions, or pharmacodermias, are the most common form of adverse drug reactions (ADR). It was our interest to know their epidemiological behavior in a tertiary hospital level in Mexico. We stablished the frequency of ADR in 61 infants and adults hospitalized patients and those seen in the outpatient Dermatology Clinic at the National Institute of Cardiology Ignacio Chávez in Mexico City (INCICh) over a period of 10 years. The most frequently diagnosed pharmacodermias were acneiform dermatitis, cutaneous hyperpigmentation and maculopapular exanthema mainly associated to prednisone, hydroxychloroquine, cephalothin, amiodarone and vitamin B-complex, although we registered less frequently more severe and hazardous reactions. These results were consistent with other reports in our country. Multiple drugs administered at a time was an important causative factor for the ADR. It is necessary for every practitioner to develop skills that permit the identification of these dermatoses in order to correctly manage each case and diminish the morbimortality associated.

Pediatric dermatologic emergencies.

Provide an overview of recent findings and recommendations for the presentation, diagnosis, and management of pediatric dermatologic emergencies. Updated information on optimal diagnosis and treatments for pediatric dermatologic emergencies because of infection, reactive infectious mucocutaneous eruption, and serious cutaneous adverse reactions are covered. Pediatric dermatologic emergencies require prompt diagnosis and management. This review covers new agents and techniques for management and diagnosis.

Dietary options for diagnosis of cutaneous adverse food reactions

Diet is critical for the diagnosis of cutaneous adverse food reactions in dogs and cats. The diagnostic process consists of the elimination trial, where a diet the patient has never been exposed to or with reduced allergenicity (elimination diet) is fed for a number of weeks exclusively. If clinical signs improve, this is followed by a challenge phase to confirm the diagnosis and identify the food triggers in each patient. Therefore, choosing the right elimination diet is very important in obtaining a reliable diagnosis and deciding on the best feeding plan for long-term management. This paper reviews the different options for canine and feline elimination diets and discusses their pros and cons.

An observational study on the spectrum of Cutaneous Adverse Reactions to Antitubercular drugs and their management

IntroductionTuberculosis (TB) remains a significant global health issue, ranking as the 13th leading cause of death worldwide. Management of tuberculosis requires administration of multiple drugs for varied duration which increases the risk of developing adverse reactions. Among various adverse reactions are cutaneous adverse reactions (CARs) which can be immune mediated or non immune mediated. Aim1. To study the clinical, epidemiological, and morphological characteristics of cutaneous adverse reactions resulting from antitubercular treatment. 2. To study the outcomes of cutaneous adverse reactions to antitubercular therapy using the Modified Hartwig and Seigel severity assessment scale and rechallenge protocol, and assess the effectiveness of management strategies. Methodology: A longitudinal observational study was conducted over a period of 1 year at department of Pulmonology and Dermatology at tertiary care institute to assess CARs in patients on antitubercular treatment. Rechallenge was done in eligible patients. ResultsAmong 3164 TB patients on anti-tubercular treatment (ATT), 56 developed CARs, yielding an incidence rate of 1.77% per year. The study found female preponderance, with the most affected age groups being 21-30 and 41-50 years. Most CARs occurred within the first 30 days of ATT initiation, predominantly manifesting as maculopapular rash. Factors such as multiple medication use, diabetes, elderly age, and positive HIV status were associated with CARs. Ethambutol was identified as the most frequently implicated drug in the occurrence of cutaneous adverse reactions (CARs) upon rechallenge. ConclusionEffective management of CARs involves appropriate treatment, careful monitoring, and rechallenge protocols to identify culprit drugs while minimizing the risk of severe reactions.Upon complete resolution of initial adverse reaction, one must do rechallenge meticulously to pinpoint culprit drug and ensuring effective tuberculosis treatment.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome with Multiple Drugs (Leflunomide and Cefuroxime): A Case Report

Background: Adverse Drug Reactions (ADRs) are unexpected reactions to a medicine administered in the correct manner and at the proper dosage. Drug Rash with Eosinophilia and Systemic Symptoms syndrome (DRESS syndrome) is a Severe Cutaneous Adverse Reaction (SCAR) type of ADR with complicated clinical features involving several organ systems of the body; frequently involved organs are the liver, kidney, lungs, and other organs. Prompt recognition and correct diagnosis, followed by withdrawal of the causative agent, can promote appropriate treatment, accelerate recovery, and reduce the related morbidity and mortality. Case presentation: We have, herein, presented a case of a 42-year-old female with a history of leflunomide intake for plantar fasciitis. The patient subsequently developed fever, gastrointestinal tract disturbance, facial edema, liver injury, skin rash, hematologic abnormalities (eosinophilia), hepatosplenomegaly, and lymph node enlargement. The probability of leflunomide-induced DRESS syndrome was rated as “definite”, with seven scores graded by RegiSCAR. The suspected causative agent was withdrawn, and the patient was managed symptomatically. Following her management and discharge, she again encountered similar complaints after administration of the cefuroxime tablet. The causality assessment of the reactions was done using the WHO-UMC scale and Naranjo’s assessment scale, and a “probable” reaction was found for both drugs. Conclusion: The presented case contributes to the existing global literature regarding exceptional clinical presentations. Leflunomide and cefuroxime drugs have the potential to cause DRESS syndrome. Thus, they should be handled cautiously, and if such a reaction occurs, it should be reported to the responsible authorities.