Metabolomic differences between exanthematous drug eruption and infectious mononucleosis.

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.

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

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Oral lichen planus-like lesions in skin of color: a review.

In dermatology, lichenoid describes lesions with a violaceous hue that is a clinical reflection of basal cell damage in the epithelium and dense mononuclear infiltrate in the sub-epithelium. The violaceous color results from pigment incontinence due to basal cell damage and the Tyndall effect. Although classically described in lichen planus, a lichenoid hue is noted in the oral mucosa in several other disorders that often lead to diagnostic dilemmas. Early and accurate diagnosis is important for the appropriate management of the underlying condition and prognostication. Dermatologists play a central role in managing such patients since, apart from the oral mucosa findings, the cutaneous features also help to significantly differentiate various conditions. Mimickers of oral lichen planus include nicotine stomatitis, oral submucous fibrosis, oral lichenoid lesions, mucosal discoid lupus erythematosus, pemphigus vulgaris, paraneoplastic pemphigus, mucous membrane pemphigoid, fixed drug eruption, plasma cell cheilitis/gingivitis, and erythema multiforme. While a detailed history and clinical examination can help reach a diagnosis in most cases, histopathology, immunofluorescence, and other relevant investigations help establish the diagnosis.

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.

Predictors of immediate and delayed cutaneous hypersensitivity reactions to paclitaxel.

Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. In this retrospective chart review at Memorial Sloan Kettering Cancer Center, we assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. 12,274 patients were treated with paclitaxel. 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction. Age (p < 0.001), race (p < 0.001), and prior history of allergy (p = 0.05) were associated with immediate hypersensitivity reactions. 147 patients (4.0%) had a rash of interest. The most common phenotypes were maculopapular (52%) and urticaria (36%). Race (p < 0.001) and history of allergy (p < 0.001) were associated with development of a cutaneous reaction. Patients with an immediate hypersensitivity reaction were more likely to have developed a delayed cutaneous reaction (OR = 1.80). Risk factors for development of immediate hypersensitivity reactions in this study were younger age, race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Identification of risk factors is critical to guide care coordination. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel. If the cutaneous reactions are bothersome to the patient, the transition of treatment from paclitaxel to nab-paclitaxel may be warranted, or a consideration of re-challenge or desensitization may be discussed.

Methotrexate-Induced Epidermal Necrosis.

A 79-year-old woman with psoriasis presented to the emergency department with new-onset eruptions on the trunk, extremities, and oral mucosa for 8-9 days. For psoriasis, she had been taking 15 mg of methotrexate weekly for over 18 years, and had discontinued folic acid a few months prior to this.

Cutaneous Toxicities With Amivantamab for Non-Small Cell Lung Cancer: A Practical Guide and Best Practices.

BACKGROUND: Amivantamab is an epidermal growth factor receptor (EGFR) and MET bispecific antibody approved for certain patients with advanced non-small cell lung cancer with EGFR variant. Cutaneous toxicities are known on-target effects of EGFR inhibition. OBJECTIVES: This article describes the occurrence and management of cutaneous toxicities in patients whose disease progressed on platinum chemotherapy treated with amivantamab. METHODS: Post hoc analysis evaluated incidence, severity, and time to first onset of rash and paronychia. Five nurses and advanced practice providers were interviewed. FINDINGS: Of 380 patients, 296 (78%) experienced treatment-related rash and/or paronychia. Paronychia (43%), rash (36%), and dermatitis acneiform (35%) were most frequent, with scalp rash reported by 17%. Treatment modifications because of rash and paronychia were infrequent. Nurses and advanced practice providers collaborate with physicians to manage cutaneous toxicities by administering comedications, modifying amivantamab dose, and educating patients.

Psoriasiform drug eruption: A case series with a review of the literature.

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.

Topical Aprepitant (HT-001): A Novel Therapy for Epidermal Growth Factor Receptor Inhibitor-Associated Papulopustular Eruptions.

Papulopustular eruptions are the most common dermatologic side effect of epidermal growth factor receptor inhibitor (EGFRI) therapy. Topical corticosteroids and oral tetracyclines are frequently used to manage these eruptions, though these treatments are limited by their adverse effects and efficacy. Results from preclinical studies suggest a role for topical aprepitant (HT-001) in the treatment of EGFRI-induced skin toxicities. Herein a case of EGFRI-induced papulopustular eruption with rapid treatment response to topical aprepitant (HT-001) 2% cream is described and the literature reviewed. J Drugs Dermatol. 2024;23(9):e173-e174. doi:10.36849/JDD.8617.

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life. METHODS: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations). RESULTS: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash. CONCLUSIONS: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.

BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.

Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions.

Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.