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A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Imatinib-induced skin rash poses a significant challenge for patients with gastrointestinal stromal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. However, the underlying mechanism of imatinib-induced skin rashes in gastrointestinal stromal tumor patients remains unclear. A total of 51 patients (27 with rash and 24 without rash) were enrolled in our study. Blood samples were collected concomitantly with the onset of clinical manifestations of rashes, and simultaneously collecting clinical relevant information. The imatinib concentration and untargeted metabolomics were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. There were no significant differences in age, gender, imatinib concentration and white blood cells count between the rash group and the control group. However, the rash group exhibited a higher eosinophil count (P<0.05) and lower lymphocyte count (P<0.05) compared to the control group. Untargeted metabolomics analysis found that 105 metabolites were significantly differentially abundant. The univariate analysis highlighted erucamide, linoleoylcarnitine, and valine betaine as potential predictive markers (AUC≥0.80). Further enriched pathway analysis revealed primary metabolic pathways, including sphingolipid signaling pathway, sphingolipid metabolism, cysteine and methionine metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, and biosynthesis of amino acids. These findings suggest that the selected differential metabolites could serve as a foundation for the prediction and management of imatinib-induced skin rash in gastrointestinal stromal tumor patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear., Methods: Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups., Results: Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively)., Conclusions: The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST., (© 2024. The Author(s).)

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy. Skin rashes and other side effects, together with poor efficacy led to a drawback of the therapeutic, but modified recIL-2 molecules are on the rise to treat both cancer and inflammatory diseases such as autoimmunity. Still, pathophysiological mechanisms of recIL-2-induced skin rashes are not understood. In the study reported here, a hypothetical literature-based immune-related adverse outcome pathway (irAOP) was developed to identify possible key cells and molecules in recIL-2-induced skin rash. Using this approach, a hypothesis was formed that the induced immune response predominantly is Type 2-driven by T-helper and innate lymphoid cells, leading to the occurrence of cutaneous side effects during recIL-2 therapy. This paper further discusses mechanisms beyond the proposed irAOP which might add to the pathology but currently are less-studied. Together, this hypothetic irAOP forms a basis to clarify possible cellular and molecular interactions leading to recIL-2-induced skin rash. This might be used to adapt existing or develop new test systems to help predict and prevent cutaneous side effects in future IL-2-based or similar therapies.

Background: Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed., Materials and Methods: A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3 mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography-mass spectrometry metabolomics., Results: A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA-cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D-glutamine and D-glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle., Conclusions: The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Among patients with hematopoietic stem cell transplants, infections, particularly multidrug-resistant infections, pose a grave threat. In this setting, penicillin allergy labels are both common and harmful. Though the majority of patients who report penicillin allergy can actually tolerate penicillin, penicillin allergy labels are associated with use of alternative antibiotics, which are often more broad spectrum, less effective, and more toxic. In turn, they are associated with more severe infections, multidrug-resistant infections, Clostridium difficile, and increased mortality. Evaluating penicillin allergy labels can immediately expand access to preferred therapeutic options, which are critical to care in patients with recent hematopoietic stem cell transplants. Point-of-care assessment and clinical decision tools now exist to aid the nonallergist in assessment of penicillin allergy. This can aid in expanding use of other beta-lactam antibiotics and assist in risk-stratifying patients to determine a testing strategy. In patients with low-risk reaction histories, direct oral challenges can be employed to efficiently delabel patients across clinical care settings. We advocate for multidisciplinary efforts to evaluate patients with penicillin allergy labels prior to transplantation., (© 2024 Wiley Periodicals LLC.)

The present case series examined five instances of psoriasiform drug eruption diagnosed between 2014 and 2022 at the study site and 23 cases of drug eruption manifesting psoriasiform lesions which had been reported between 1986 and 2022. The causative drug, distribution of the skin eruptions, clinical latency to eruption, treatment course, and histopathological findings were investigated. The most common causative agents were calcium channel blockers (CCB) (64.5%). Of the 28 cases of psoriasiform drug eruption for which details of the eruption sites were reported, 46.4% occurred on the face, which was slightly higher than the usual distribution of psoriasis. CCB were responsible for 80.0% of the cases of facial skin rash. The mean time from the administration of the suspected drug to eruption onset was 25.0 months (range: 0.5-120 months; median: 13.0 months). In all the cases, the skin rash improved after the causative drug was discontinued. CCB were the most common causative agent, and the eruptions more commonly occurred on the face than in normal psoriasis, suggesting that it is especially important to confirm whether there is a history of CCB administration in psoriasis patients with extensive, facial skin eruptions., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic severe cutaneous adverse reaction that may be potentially life-threatening. Recently, a simple scoring system for the early screening of DRESS patients was derived by combining hsCRP levels, the eosinophil count, and the total body surface area (CET score). The objectives of this study were validating the CET score, and calculating its lead time advantage and cost-benefits compared to RegiSCAR scoring., Methods: This is a prospective observational case-control study, where 110 consecutive patients diagnosed with drug-induced maculopapular exanthema (MPE) were recruited during the 18 months of the study period. Patients were classified as cases (DRESS) and controls (MPE) using RegiSCAR score cut-off 2 (possible DRESS). They were also simultaneously screened using the CET score, based on which patients were classified as positive or negative. They were subsequently followed up on Day 15 for a second comparison and assessment of lead time and at 3 and 6 weeks to evaluate clinical response., Results: Seventy cases and 40 controls were recruited. At a cut-off of >2.12, the CET score had a sensitivity of 94.3%, a specificity of 60%, a positive predictive value (PPV) of 80.5%, and a negative predictive value (PPV) of 85.7%. The median delay in diagnosing DRESS using RegiSCAR was around 14.5 hours. There was a median cost benefit of 12.1 USD in favor of the CET score., Conclusions: The CET score had good diagnostic performance in screening DRESS patients with a lead time of 14.5 hours and fewer costs incurred., (© 2024 the International Society of Dermatology.)

Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest None to declare.

Background: Cutaneous manifestations of drug-induced type IV reactions vary widely, with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) being a less common presentation. Corticosteroids (CS), primarily known for their anti-inflammatory effects, rarely induce hypersensitivity reactions., Objective: The aim of this case series is to report four cases of SDRIFE following systemic prednisolone therapy and to review existing CS classification proposals to better understand cross-reactivity of CS., Patients/methods: Patients recruited at a German dermatology centre underwent allergologic evaluation including prick and patch testing with various CS. Positive cases underwent oral challenge testing with alternative agents. The classification systems of Coopman et al. and Baeck et al. were taken into account., Discussion: Despite a paucity of literature, CS-induced type IV reactions do occur, including SDRIFE. Classification systems based on chemical structure provide insight into cross-reactivity patterns. Provocation tests with alternative CS highlight the complexity of managing CS hypersensitivity., Conclusion: SDRIFE may develop following systemic prednisolone therapy. Classification systems are helpful in understanding cross-reactivity and help in the selection of alternative preparations but are not always reliable. Individualised assessment is crucial for managing CS hypersensitivity, with consideration of alternative agents and emergency use of CS when necessary., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone., Case Presentation: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic., Conclusions: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing., (© 2024. The Author(s).)

This column is the second of a 3-part series describing cases where general medical knowledge, including psychiatric and clinical pharmacology, were instrumental in determining dereliction and direct cause in a malpractice suit. This case summarizes how lamotrigine can cause dangerous consequences if its pharmacology is not properly understood. The case also illustrates how the 4 Ds of a forensic malpractice suit were met in this case. First, there was duty on the part of the prescriber which, if followed, would have prevented or minimized the damages experienced by the patient. Dereliction in the performance of a patient-physician treatment contract was a direct cause of the development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in this patient. An immune-mediated reaction to lamotrigine or one of its metabolites has been extensively reported in the literature, with the risk of this reaction increasing at higher doses and with more rapid titration, fulfilling the elements of direct cause. Dereliction implies a deviation from the standard of care. On the basis of the clinical information from the package insert, more likely than not a deviation from the standard of care occurred in this case when lamotrigine was titrated faster than recommended by the package insert., Competing Interests: Over his 45-year career, S.H.P. has worked with over 145 pharmaceutical and biotech companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant, on the advisory board, or on the speaker’s bureau for Alkermes, BioXcel, and Janssen. There were no clinical trial and study contracts during the 2 years preceding this paper, but any would have been with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita. D.D.M. declares no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been recommended as a first-line treatment of EGFR-positive non-small cell lung cancer (NSCLC). Skin rash is one of the most common side effects of osimertinib, and can have an impact on patients' quality of life and follow-up. However, there are few reports on the safety and efficacy of switching therapy with osimertinib and the other three generations of TKIs. In this paper, we present a case of NSCLC with an EGFR exon 19 deletion (19del) and MET gene amplification who developed a severe rash after 2 months of treatment with osimertinib that did not recur after switching to replacement therapy with aumonertinib. Our findings indicate that aumonertinib is as effective as osimertinib in treating EGFR19del, while also exhibiting a lower occurrence of adverse skin reactions. This may result in an improved quality of life for patients.

Purpose: Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood., Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays., Results: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo., Conclusions: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions., (©2024 The Authors; Published by the American Association for Cancer Research.)

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.

Background: Oncological therapies can cause a variety of mucocutaneous adverse events. Exanthematous adverse events can be challenging in the context of the urgent need for cancer treatment due to their spread, sometimes rapid progression, and mucous membrane or organ involvement., Materials and Methods: This article provides an overview of the most important exanthematic dermatoses as side effects of modern drug-based tumor therapies with diagnostic and therapeutic information for clinicians, taking into account the current literature and guidelines., Results: Exanthematous adverse events of immune checkpoint inhibitors, EGFR antagonists, kinase inhibitors, bispecific T‑cell engagers, and the CCR4 inhibitor mogamulizumab are reviewed in detail., Conclusions: Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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 6.71 days). 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 4-6 week 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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for EGFR-mutated non-small cell lung cancer (NSCLC) is unclear. Previous studies have shown that EGFR-TKIs have excellent anti-tumor activity. However, almost all studies on neoadjuvant EGFR-TKI treatment for EGFR-mutated NSCLC have been non-randomized controlled trials with small sample sizes and different methods of statistical analysis, which may lead to a lack of valid metrics to assess the feasibility and safety of neoadjuvant EGFR-TKI treatment. This meta-analysis aimed to assess the efficacy and safety of neoadjuvant EGFR-TKI treatment for NSCLC patients with EGFR mutations., Methods: Relevant studies were systematically searched in PubMed, Embase, and Web of Science databases. Results including objective response rate (ORR), complete resection rate (R0), downstaging rate, pathological complete response (PCR), major pathological response (MPR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were used for further analysis., Results: This meta-analysis ultimately included 11 studies involving 344 patients with EGFR-positive mutations in NSCLC. In terms of tumor response, the pooled ORR was 57% (95% CI: 42%-73%), and in the Osimertinib subgroup, the pooled ORR was 80% (95% CI: 63%-98%). Analysis of studies that reported a downstaging rate showed the pooled downstaging rate of 41% (95% CI: 9%-74%) and the pooled downstaging rate of 74% (95% CI: 22%-100%) in the Osimertinib subgroup. In terms of surgical outcomes, the pooled pCR rate was 3% (95% CI: 0%-7%), the pooled MPR rate was 11% (95% CI: 6%-17%), and the pooled R0 resection rate was 91% (95% CI: 85%-95%). The most common adverse events associated with neoadjuvant therapy were rash and diarrhea. The pooled incidence of any grade of rash was 47.1% (95% CI: 25.4%-69.3%), and the pooled incidence of grade ≥ 3 rash was 0.6% (95% CI: 0.0%-2.5%). The pooled incidence of diarrhea of any grade was 28.8% (95% CI: 14.4%-45.4%), with the pooled incidence of grade ≥ 3 diarrhea of 0.2% (95% CI: 0.0%-1.6%). The pooled incidence of ≥ grade 3 adverse events was significantly lower., Conclusions: Our meta-analysis confirmed the efficacy and safety of neoadjuvant EGFR-TKIs for the treatment of NSCLC patients with EGFR-positive mutations and that third-generation EGFR-TKIs were superior to first- and second-generation EGFR-TKIs in terms of shrinking tumor volume and lowering tumor stage; however, future large-scale and multicenter randomized controlled trials are needed to confirm this conclusion., Systematic Review Registration: PROSPERO CRD42023466731., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To draw clinical attention to rashes caused by lacosamide., Methods: This retrospective analysis included patients admitted to the Department of Pediatrics, Second Affiliated Hospital of Xi'an Jiaotong University between January 2021 and September 2023. We focused on patients who developed rashes after lacosamide treatment and analyzed all patients who exhibited rashes after lacosamide treatment to analyze the risk factors., Results: In total, 190 patients received lacosamide, of whom four developed allergies (2.1 %). Three patients had severe rashes, and two patients had high fever. All of these adverse events improved after the withdrawal of lacosamide. Of the 13 patients reported to date, including the four patients in this study, eight used various antiseizure medicines, including seven patients who used four or more antiseizure medicines. Four patients underwent testing for HLA-B*1502, and two patients were positive. Patients developed rashes within 1-10 days after treatment initiation, and the duration of the rash ranged 2-37 days., Conclusions: Lacosamide-induced rash was detected in 2.1 % of patients in our cohort. Rashes are potentially serious, and prompt evaluation is required. Rashes are more likely to occur when multiple antiseizure medicines are used simultaneously, typically within 10 days of treatment initiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Acneiform rash is frequently observed in patients undergoing cancer treatment with anti-epidermal growth factor receptor (EGFR) antibody drugs and can often necessitate treatment discontinuation. However, the specific changes in skin parameters resulting from anti-EGFR antibody drug administration are poorly understood. Therefore, this study aimed to longitudinally and quantitatively evaluate the changes in skin parameters (transepidermal water loss [TEWL], hydration level, and sebum level) caused by anti-EGFR antibody drugs and investigate their potential as control markers for skin disorders., Methods: This prospective study included 12 patients with colorectal cancer who received anti-EGFR antibody drugs for the first time. The assessment items included the grade of acneiform rash and skin parameters (TEWL, hydration level, and sebum level), which were observed for up to 6 weeks after administration of the medication., Results: The enrolled patients were classified into two groups based on the grade of acneiform rash caused by anti-EGFR antibody drugs: "Grade 1 and lower," and "Grade 2 and higher." The skin parameters were compared between these groups. The results showed that in the "Grade 2 and higher" group, TEWL in the face (at week 2 of administration), chest (baseline, weeks 2 and 6 of administration), and back (at week 2 of administration) were significantly higher than those in the "Grade 1 and lower" group. However, the two groups showed no significant differences in hydration or sebum levels at any time point., Conclusion: TEWL can serve as a marker for acneiform rashes induced by anti-EGFR antibody drugs during cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)., Methods: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS)., Results: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively., Conclusion: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Byoung Chul Cho has received research funding from MOGAM Institute, LG Chem, Oscotec Inc., Interpark Bio Convergence Corp, GI Innovation, GI Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, BridgeBio Therapeutics, Yuhan Corporation, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center and Vertical Bio AG. He has received consulting fees from Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono Pharmaceutical, Onegene Biotechnology, Yuhan Corporation, Pfizer, Eli Lilly, GI Cell, Guardant Health, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi. He receives royalty from Champions Oncology, Crown Bioscience, Imagen and serves on the advisory board of Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotech Inc, J INTS BIO, Therapex, Gilead, Amgen. He was an invited speaker for ASCO, AstraZeneca, Guardant Health, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, and Pfizer. He is on the board of directors for J INTS BIO. He is an employee of Yonsei University Health System and the founder of the DAAN Biotherapeutics. He owns stocks of TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp., and J INTS BIO. Ji-Youn Han reports research funding from Pfizer, Takeda, ONO, Roche; consulting fees from AstraZeneca, Janssen, Amgen, Oncobix, Merck, Novartis, Abion, Takeda, J INTS BIO and honoraria for lectures from AstraZeneca, Janssen, Takeda, Merck, Yuhan Corporation, Novartis and Pfizer and payment for expert testimony from AstraZeneca He participated in Data Safety Monitoring Board for AstraZeneca, Janssen, J INTS BIO. Ki Hyeong Lee reports grants from Merck Serono. He has received consulting fees from MSD, Pfizer, Eli Lilly, Yuhan Corporation, AstraZeneca, BMS. Yun-Gyoo Lee reports honoraria for lectures from AstraZeneca, MSD, Lilly, Boehringer Ingelheim and Yuhan. He participated in Data Safety Monitoring Board or Advisory Board for BeiGene, Dakeda, Guardant Health, Yuhan, Ono and Novartis. Dong-Wan Kim reports research funding to his institution from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, BMS, BridgeBio Therapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan Corporation, and honoraria from the Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group. He reports travel support for attending meetings for the International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. He provides medical writing assistance to Amgen, AstraZeneca, Boehringer-Ingelheim, BridgeBio Therapeutics, BMS, Chong Keun Dang, Daiichi-Sankyo, GSK, Pfizer, MSD, Merck, Merus, Novartis, Roche, Takeda, Yuhan Corporation. He participated in advisory boards for Amgen, AstraZeneca, BMS/Ono Pharmaceutical, Daiichi-Sankyo, GSK, Janssen, Meck, MSD, Pfizer, SK Biopharm, Takeda. He is on the Board of Directors for Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, and Korean Society of Medical Oncology. He is a scientific advisor for Health Insurance Review and Assessment Service, Republic of Korea. Eun Kyung Cho reports participation in data safety monitoring meeting for Yuhan Corporation for this clinical trial and received study drugs for conducting this clinical trial from Yuhan Corporation. Young Joo Min reports research funding from AstraZeneca, MSD, Merck, Ono Pharmaceutical, Yuhan Corporation, Amgen, Roche and honoraria from AstraZeneca, MSD, Merck, and Ono Pharmaceutical. Na Mi Lee, Jangyoung Wang, and Hyejoo Park are employees of Yuhan Corporation. Myung-Ju Ahn received consulting fees and research funding from AstraZeneca, Eli Lilly, MSD, Merck, Ono Pharmaceutical, Takeda, Yuhan Corporation, Amgen, Novartis, Roche, Alpha-Pharmaceuticals, and honoraria from AstraZeneca, Eli Lilly, MSD, Merck, Ono Pharmaceutical, Takeda, Yuhan Corporation, Amgen, Novartis and Roche. All other authors have no relevant relationships to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

On July 23, 2022, the World Health Organization (WHO) declared the rapid global spread of Mpox (formerly known as monkeypox) a public health emergency of international concern. A 28-year-old male patient with severe Mpox infection and HIV stage 3 (AIDS) is presented., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: This study aimed to explore the clinical characteristics of apalutamide-associated skin rash and management of skin rash in real-world Chinese patients with prostate cancer., Methods: We investigated 138 patients with prostate cancer who received apalutamide in the Second Hospital of Tianjin Medical University from January 2022 to March 2023. The primary end points were the incidence of skin rash and the time to skin rash. The second end points were the grade of skin rash, the time to remission, the rate of recurrence of skin rash, clinical risk factors and management of skin rash., Results: One hundred patients were analyzed. Patients were a median of 73 years old (IQR 68-77.75). Thirty-two patients (32%) developed apalutamide‑associated skin rash. The median time to incidence and remission of skin rash were 57.5 and 11.5 days, respectively. Of 32 skin rash, 27 patients had apalutamide therapy maintained after rash remission. There were seven patients having recurrence of skin rash. By multivariable logistic regression analysis, we revealed that hypertension history (OR 3.22, 95% CI 1.09-9.53, p = 0.035), bad life-styles (OR 3.29, 95% CI 1.11-9.8, p = 0.032), ECOG ≥ 1 (OR 3.92, 95% CI 1.33-11.55, p = 0.013), and high tumor burden (OR 3.13, 95% CI 1.07-9.14, p = 0.037) were independently associated with higher incidence of skin rash., Conclusion: Nearly one-third of Chinese patients experienced skin rash after taking apalutamide in our study. The poor health patients might have a higher incidence of apalutamide-associated skin rash., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study., Methods: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months., Results: This study included 48 participants with previously untreated FL grade 1-3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1-21 cycle 1; 20 mg, cycles 2-12), rituximab (375 mg/m 2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%-91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%-76.4%). One death occurred unrelated to disease progression. Grade 3-4 adverse events were observed in 64.6%, including 50% with grade 3-4 rash., Conclusions: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257)., (© 2023 American Cancer Society.)

Abstract: A 38-year-old man presented with fever, cough, and jaundice. Four days before, he had started taking amoxicillin/clavulanic acid. He subsequently developed a morbilliform rash, and, according to clinical features and blood analyses, a diagnosis of mononucleosis with Epstein-Barr virus-associated antibiotic-induced exanthema and secondary hemophagocytic lymphohistiocytosis was made. A skin biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with interface dermatitis and many foamy macrophages in the papillary dermis and around the vessels of the superficial dermal plexus. A blood lipid test uncovered marked hypercholesterolemia and hypertriglyceridemia. After treatment with dexamethasone and immunoglobulin, the skin rash, liver function, and lipid profile progressively improved. Xanthomatous cells have been observed in skin biopsies of acute graft-versus-host disease with liver involvement, and these cells have been suggested to represent a clue to the presence of hepatic disease. In our case, underlying cholestatic hepatopathy with hyperlipidemia was present. We believe that the incidental finding of foamy cells in graft-versus-host disease cases and in our case are likely related to the presence of severe liver disease with cholestatic hepatopathy and secondary hyperlipidemia in different background conditions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUNDDisease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus.METHODSTwo randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2Δ30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3Δ30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2Δ30 or rDEN3Δ30 strain.RESULTSTV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype.CONCLUSIONSTV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model.TRIAL REGISTRATIONClinicalTrials.gov NCT02317900 and NCT02873260.FUNDINGIntramural Research Program, NIH (contract HHSN272200900010C).

Competing Interests: Competing interests: None declared.

Introduction: The tetravalent live virus vaccine developed by Takeda called Qdenga® is available in Argentina and approved for use from 4 years of age without age limit. The objective was to describe clinical characteristics and evolution of the initial reports of rash after the first dose., Material and Methods: The records of Events Supposedly Attributable to Vaccination or Immunization Reported in a Private Vaccination Center were reviewed between 15/11/2023 and 12/12/2023. Cases with skin rash that occurred outside the application site area were included. The main variables analyzed were age, sex, history of dengue, characteristics of the skin rash, accompanying symptoms, time elapsed from vaccination to the onset of the rash and evolution. The incidence of rash was calculated: cases/10,000 vaccinated., Results: Out of 12 551 doses applied, 15 cases were included. Median age: 35 years, female sex: 8/15. Clinical forms of presentation: generalized micropapular (3/15), maculopapular (3/15), scarlatiniform (1/15), urticarian (1/15), multiform (1/15), erythematous in the face (1/15) and unspecified (5/15). Most common concomitant symptoms: pruritus (5/15), fever or low-grade fever (6/15), headache (3/15), retro-ocular pain (2/15), asthenia (2/15). Three cases reported a history of dengue. The median number of days of rash presentation was 8 days' postvaccination. All patients progressed favorably. The overall incidence was 1.2/1000 vaccinated., Conclusions: In passive surveillance, after more than 12 000 first doses administered, the presence of rash was observed in less than 0.12% of those vaccinated. Everyone evolved favorably.

Background: We investigated naporafenib (LXH254), a pan-RAF kinase inhibitor, with or without spartalizumab, in patients with advanced solid tumors harboring MAPK pathway alterations., Methods: This first-in-human phase 1 study had two dose-escalation arms: single-agent naporafenib (starting at 100 mg once-daily [QD]) and naporafenib (starting at the recommended dose/regimen)/spartalizumab (400 mg every 4 weeks). The naporafenib/spartalizumab dose-expansion part enrolled patients with KRAS-mutated non-small cell lung cancer (NSCLC) and NRAS-mutated melanoma. The primary objectives were to establish the maximum tolerated doses (MTD)/recommended doses for expansion (RDE) and evaluate tolerability and safety., Results: A total of 142 patients were included in the naporafenib dose-escalation (n = 87), naporafenib/spartalizumab dose-escalation (n = 12) and naporafenib/spartalizumab dose-expansion (n = 43) arms. The MTD/RDE of naporafenib was 600 mg twice-daily (BID). In naporafenib escalation, five patients experienced 7 dose-limiting toxicities: decreased platelet count (1200 mg QD); neuralgia, maculopapular rash, pruritus (600 mg BID); increased blood bilirubin, hyponatremia, peripheral sensory neuropathy (800 mg BID). No DLTs occurred in the naporafenib/spartalizumab arm: the RDE was established at 400 mg BID. The most common treatment-related adverse events were rash and dermatitis acneiform (each 24.1%; naporafenib), nausea and pruritus (each 33.3%; naporafenib/spartalizumab; escalation) and rash (39.5%; naporafenib/spartalizumab; expansion). Naporafenib reduced DUSP6 expression in tumors. Two partial responses (PRs) occurred in naporafenib escalation, and 1 complete response and 3 PRs in the naporafenib/spartalizumab NRAS-mutated melanoma and KRAS-mutated NSCLC arms, respectively., Conclusions: Naporafenib, with or without spartalizumab, showed an acceptable safety profile, pharmacodynamic activity and limited antitumor activity. Additional naporafenib combination therapies are currently under investigation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Filip Janku received research support from Astex, Novartis, BioMed Valley Discoveries, Fore Bio, Deciphera, Bristol-Myers Squibb, Asana, Ideaya Biosciences, Sanofi, Merck, F-star, JSI Innopharm, Bioxcel, Lilly, Bicara, PureTech Health, FujiFilm Pharmaceuticals, Piqur, Sotio, Synlogic, NextCure and Hutchinson Medipharma; served on the Scientific Advisory Boards of Ideaya Biosciences, Synlogic, Sotio, Puretech Health, Deciphera, Crown Bioscience, Asana, Fore Bio, Novartis, Bicara and PegaOne; served as a paid consultant for Mersana Therapeutics, Flame Bio, Cardiff Oncology, MedinCell and Immunomet; has ownership interests in Cardiff Oncology and Monte Rosa Therapeutics; and has the leadership position in Monte Rosa Therapeutics. Tae Min Kim received consulting fees or honoraria for lectures from AstraZeneca, IMBDx, Inc., Janssen, Regeneron, Samsung Bioepis, Takeda and Yuhan; had advisory role for AstraZeneca, Janssen, Regeneron and Takeda; and received a research grant from AstraZeneca-KHIDI outside this work. Gopakumar Iyer reports consulting or advisory role for Bayer, Janssen, Mirati Therapeutics, Basilea Pharmaceutica, Flare Therapeutics and Aadi Bioscience; speakers' bureau for Gilead Sciences and Lynx Group; and research funding (to institution) from Mirati Therapeutics, Novartis, Janssen, Seattle Genetics, LOXO at Lilly and Aadi Bioscience. Anna Spreafico has received consulting fees from Merck, Bristol-Myers Squibb, Oncorus, Janssen, and Medison & Immunocore; and funding support for clinical trials paid to the Institution from Novartis, Bristol-Myers Squibb, Symphogen, AstraZeneca/Medimmune, Merck, Bayer, Surface Oncology, Northern Biologics, Janssen Oncology/Johnson & Johnson, Roche, Regeneron, Alkermes, Array Biopharma/Pfizer, GSK, NuBiyota, Oncorus, Treadwell and Amgen. Elena Elez has received personal speaker honoraria from Organon and Novartis; and personal advisory board honoraria from Amgen, Bayer, Hoffman-La Roche, Merck Serono, Sanofi, Pierre Fabre, MSD and Servier. Noboru Yamamoto reports research grants from Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic, InventisBio and Rakuten Medical; advisory roles for Eisai, Takeda, Boehringer Ingelheim, Cmic, Chugai, Merck and Healios; and honoraria as a Speaker from ONO, Chugai, Daiichi-Sankyo and Eisai. Anthonie J. van der Wekken reports grants and other support from AstraZeneca, Pfizer, Roche and Takeda; grants from Boehringer Ingelheim; and other support from Agena and Janssen, outside the submitted work. All payments were made to the University Medical Centre Groningen. Paolo Antonio Ascierto has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Sandoz, Immunocore, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune, Bayer and Erasca; received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer and Sanofi; and travel support from Pfizer, Bio-Al Health and Replimmune. Frederik Marmé reports personal fees from GSK, Roche, Novartis, AstraZeneca, MSD, Vaccibody, Gilead Sciences, Eisai, Pfizer, Myriad, Genomic Health, Seagen, Daiichi Sankyo, Pierre Fabre, Agendia, Lilly and Clovis outside the submitted work. Jean-Jacques Kiladjian reports consulting fees from GSK and Abbvie; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Novartis and AOP Health; participation on a data safety monitoring board or advisory board for Incyte and BMS. Sumit Basu, Fabienne Baffert, Amparo Buigues, Vesselina Cooke and Jaeyeon Kim are employees and stockholders of Novartis. Chi Chen and Elisa Giorgetti are employees of Novartis. Fiona McCarthy is a previous employee and a stockholder of Novartis. Michele Moschetta is a previous employee and a stockholder of Novartis and has submitted a patent application related to LXH254. Reinhard Dummer reports intermittent, project-focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer and touchIME outside the submitted work. Maja de Jonge and Michela Maur report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Adverse drug reactions (ADR) are considered any harmful and unintended side effects associated with the use of a drug at the usual therapeutic dose, in which skin is involved in most cases. Therefore, the availability of epidemiological information on reactions, reaction patterns, and their causative drugs can be helpful in timely diagnosis and necessary measures, such as caution in prescribing causative drugs to prevent these types of reactions., Methods: In this retrospective descriptive study, the archived files of patients with dermatoses due to ADR referred to Taleghani University Hospital, Urmia, Iran, during 2015-2020 were studied. Patterns and frequency of skin reactions, demographic data, and the frequency of chronic comorbidities were identified., Results: A total of 50 patients with drug-induced skin rash were found, of which 14 were male (28%) and 36 were female (72%). Skin rashes were most frequently found in patients aged 31-40 years. In 76% of patients, there was at least one chronic underlying disease. The most common reaction pattern was maculopapular rash (44%), and the most common causative drugs were antiepileptic drugs (34%) and antibiotics (22%). Mortality was found in 4 cases, which was due to antibiotics and antiepileptic drugs that caused toxic SJS/TEN and erythroderma. The hospital stays were highest in SJS and lowest in a maculopapular rash., Conclusion: Knowledge about the epidemiology and the frequency of adverse drug reactions may be helpful in increasing the awareness of physicians for correct and rational drug prescriptions, which can reduce unnecessary hospital referrals and treatment costs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This meta-analysis investigated the efficacy, safety, and tolerability of lamotrigine versus placebo in preventing relapse and recurrence of mood episodes in women of childbearing age with bipolar I disorder. Following up to 16 weeks' open-label lamotrigine treatment, responders were randomized to double-blind treatment, including lamotrigine 100-400 mg/day or placebo, in four trials of up to 76 weeks. Women aged 18-45 years who received ≥ 1 dose of study treatment and had ≥ 1 efficacy assessment in the double-blind phase were pooled for efficacy analysis. The primary outcome was median time to intervention for any mood episode (TIME). Of 717 eligible women in the open-label phase, 287 responded and were randomized to lamotrigine (n = 153) or placebo (n = 134). The randomized group had a mean (SD) of 2.0(2.02) manic and 2.5(2.02) depressive episodes in the 3 years before screening. Median TIME was 323 days with lamotrigine and 127 days with placebo (HR 0.69; 95% CI 0.49, 0.96; p = 0.030). Lamotrigine delayed time to intervention for any depressive episode (HR 0.59; 95% CI 0.39, 0.90; p = 0.014) with no treatment difference for manic episodes (HR 0.91; 95% CI 0.52, 1.58; p = 0.732). 2/717 (< 1%) participants experienced serious rash-related adverse events (AEs) during the open-label phase, and 52/717 (7%) had non-serious rash-related events leading to study withdrawal. Incidence of AEs and AEs leading to withdrawal were similar between lamotrigine and placebo groups. Lamotrigine delayed relapse and recurrence of mood episodes, largely by preventing depressive episodes, and was well tolerated in women of childbearing age., Competing Interests: Conflict of interest Eduard Vieta, has received grants from AB-Biotics, Dainippon Sumitomo Pharma, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda; has received payment or honoraria from Abbott, Angelini, Cambridge University Press, Casen-Recordati, Elsevier, Galenica, GSK, Janssen, Lundbeck, Oxford University Press, Organon, Otsuka, and Sage; and has served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Angelini, Biogen, Celon, Gedeon Richter, GH Research, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, Shire, Sunovion, and Takeda (all outside the submitted work). Sanman Ghorpade, Angshuman Sarkar, Abhay Phansalkar, and James Cooper are employees of, and hold stocks in, GSK group of companies. Arunangshu Biswas is an employee of GSK., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash., Methods: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed., Results: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P  = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P  = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P  < .0001), emotions (58.33 vs 15.48, P  < .0001), functioning (46.67 vs 13.33, P  < .0001) and composite (52.60 vs 14.06, P  < .0001)., Conclusion: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.