Fixed drug eruptions (FDE) are drug-induced skin reactions that repeatedly occur at the same anatomical site. The skin lesions are usually clear hyperpigmented patches that may develop into blisters. The skin response involves type IV delayed hypersensitivity reactions and is caused by drug-specific memory CD8 T-cells located at the affected skin site. Levocetirizine, an H1-selective second-generation piperazine antihistamine, has a good safety profile and is used to treat the skin reactions. Its nonprescription availability leads to self-medication and unrecognised adverse drug reactions (ADR). FDE due to levocetirizine, as well as with cetirizine, is less common in the literature. This case was reported to our ADR Monitoring Center and causality was assessed as probable and preventable. This case shows that antihistamines such as levocetirizine can trigger FDE in susceptible individuals. Improving clinical awareness through robust Pharmacovigilance activities, educating patients about triggers, and discouraging self-medication are crucial for preventing recurrence.

Severe cutaneous adverse drug reactions (SCARs), comprising mainly Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, generalized bullous fixed drug eruption (GBFDE), are rare adverse reactions to drugs, hampered by a significant morbidity and mortality. Due to their unpredictable nature, they completely disrupt the benefit-risk balance of drug prescription. Nonetheless, a partial predictability is emerging. Firstly, all drugs do not carry the same risk for SCARs. Drugs carrying the higher risk are allopurinol, carbamazepine, lamotrigine, iodinated contrast media, and antibiotics, particularly sulfonamides and aminopenicillins. In addition, main risk factors comprise genetic polymorphisms of the HLA system and increased drug dosage. A targeted HLA genetic screening together with drug avoidance in case of high risk allowed to reduce the incidence of SCARs associated with carbamazepine and allopurinol. Similarly, a progressive titration of lamotrigine dose allowed to reduce the incidence of SCARs associated with lamotrigine. Pharmacovigilance databases allow the quick identification of culprit drugs, together with the implementation of whistle-blowing policies. Nonetheless, they present with quantitative and qualitative limitations and their own particular biases. Pharmacoepidemiologic databases allow the computation of SCAR incidences and confirm previously identified associations between drugs and SCARs. They may also allow help to identify the main clinical risk factors, e.g., chronic renal disease and Asian ethnicity for allopurinol. Nonetheless, they are limited by measure bias and lack of clinical and biological data. Ultimately, clinical and pharmacogenomic databases allow the identification of more precise risk factors, comprising precise genetic polymorphisms, drug dosage and impaired metabolism. The combination of all allows to establish a personalized risk stratification across SCARs subtypes and drug prescriptions. Ultimately, this allows the establishment of prescribing policies and the decrease of SCARs incidence.

Triazole antifungal drugs (TADs) are widely used in clinical practice but carry a risk of severe cutaneous adverse reactions (SCARs). However, comprehensive real-world evidence regarding the comparative safety profiles of individual TADs remains limited. This research aimed to investigate and compare the real-world risk, clinical characteristics, and time-to-onset of SCARs associated with individual TADs. The SCAR cases with TADs as the primary suspect drug were identified in the FDA Adverse Event Reporting System. Disproportionality analysis and Bayesian methods were employed to detect safety signals with Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Differences of clinical features, outcomes, time-to-onset (TTO), and signal strength at the preferred term (PT) level were analyzed. A total of 1429 SCAR cases with five TADs were identified. Fluconazole showed the strongest and most consistent statistical association across all four algorithms (ROR = 5.2), followed by itraconazole. Voriconazole yielded mixed signals (positive by ROR and BCPNN only), while Posaconazole and Isavuconazole exhibited no significant SCAR signals. Voriconazole was associated with the highest mortality proportion (12.8%), followed by posaconazole (10%). The median TTO for SCARs was 8 days, with voriconazole having the longest delay (16 days). At the PT level, 45 distinct signals were identified, including high-risk manifestations such as fixed eruption (ROR = 24.43), mucosal ulceration, and SJS/TEN overlap. This study identified significant variability of SCARs signals among triazole antifungals. These findings support early risk recognition and informed antifungal selection in clinical practice.

This case series describes three serious adverse drug reactions (ADRs) reported from tertiary care teaching hospitals and analyses their seriousness and preventability. The cases included fixed drug eruption associated with paracetamol/amoxicillin exposure, Stevens-Johnson syndrome/toxic epidermal necrolysis following ceftriaxone administration, and acute renal failure after intake of a fixed-dose combination of diclofenac and paracetamol. Clinical details, suspected drugs, management, outcomes, and pharmacovigilance reporting were reviewed. Seriousness, causality, and preventability were assessed using standard pharmacovigilance criteria, including the Uppsala Monitoring Centre causality assessment approach. All three cases required hospital-based management, and two involved severe cutaneous adverse reactions requiring multidisciplinary care. The cases highlight the contribution of irrational prescribing, inappropriate drug combinations, and delayed recognition to preventable serious ADRs. Early withdrawal of the suspected drug, timely reporting to pharmacovigilance centres, multidisciplinary management, rational prescribing, adherence to clinical protocols, and patient awareness are essential to reduce recurrence and improve medication safety.

Volcanic Andisols in southern Chile severely limit pasture productivity due to their high phosphorus (P) sorption capacity. This study evaluated how contrasting P sources shape the rhizosphere microbiome of perennial ryegrass (Lolium perenne) and the pathways linking microbial community composition, plant biochemical responses, and biomass production under P-limiting conditions. A greenhouse experiment using an Andisol (Freire series) tested four P sources; Triple Superphosphate (TSP), Phosphate Rock (PR), Cattle Dung (CD), and Poultry Manure (PM); at two nitrogen (N) rates (100 and 200 mg kg[-1]) alongside no-P control that received the same two N rates and basal nutrients but no added P. Rhizosphere communities were characterized by 16S rRNA amplicon sequencing coupled with functional gene prediction (PICRUSt2), antioxidant enzyme activity and lipid peroxidation markers (superoxide dismutase, catalase, malondialdehyde), P-starvation transporter and phosphatase gene expression (LpPHT1;1, LpPHT1;4, LpPAP1), and soil chemistry. P source was the dominant driver of both plant performance and community composition, with N rate exerting a secondary, modulatory role; attenuating P-starvation gene expression at higher doses and subtly influencing community beta-diversity. Soil P availability, pH, and exchangeable aluminum were the significant drivers of community structure. Path analysis revealed that the rhizosphere microbiome had no significant direct effect on shoot P uptake but was strongly associated with reduced foliar oxidative stress (β = -0.759, p < 0.001), with its indirect effect on shoot biomass statistically consistent with mediation through this antioxidant buffering response. Organic amendments enriched predicted genes related to P mineralization and biological N-P cycling while suppressing denitrification-associated genes. These findings suggest that in high P-fixing volcanic soils, rhizosphere community shifts benefit plant growth primarily by alleviating P deficiency-induced oxidative stress rather than by directly enhancing P uptake, highlighting the agronomic value of organic amendments beyond nutrient supply alone.

Fixed drug eruption (FDE) is a distinctive cutaneous adverse drug reaction characterised by recurrent, well-demarcated erythematous plaques occurring at the same anatomical site following re-exposure to the offending drug. Although most commonly associated with antimicrobials and non-steroidal anti-inflammatory drugs, dermatological reactions related to dipeptidyl peptidase-4 inhibitors are rarely reported. We describe a man in his 50s with type 2 diabetes mellitus who developed multifocal erythematous plaques over the inframammary region shortly after initiation of sitagliptin therapy. The temporal relationship, characteristic morphology and prompt resolution following drug withdrawal supported the diagnosis of sitagliptin-induced FDE. Lesions resolved within 1 week with residual post-inflammatory hyperpigmentation. This case highlights the importance of recognising uncommon cutaneous adverse drug reactions associated with newer antidiabetic agents and emphasises the role of pharmacovigilance in improving drug safety.

The concept of tissue-resident memory T (TRM) cells has fundamentally transformed our understanding of peripheral immune surveillance. Although skin TRM biology has been extensively studied, most investigations have focused on the dermis, whereas the epidermis has traditionally been regarded primarily as a physical barrier composed predominantly of keratinocytes. However, accumulating evidence has demonstrated that the normal human epidermis harbors abundant populations of resident T cells, including both conventional and regulatory TRM cells, indicating that the epidermis is a highly specialized immunological compartment. In this review, we summarize current knowledge regarding the origin, composition, phenotype, and dynamics of human epidermal TRM cells, with particular emphasis on studies performed in human tissues. Epidermal TRM cells are enriched for CD8[+]CD69[+]CD103[+] populations and include specialized cytotoxic subsets expressing CD49a and CD101, whereas regulatory TRM cells constitute a distinct epithelial regulatory network that contributes to local immune tolerance. We also discuss recent advances demonstrating that epidermal TRM cells actively patrol the epidermis, interact closely with Langerhans cells, and participate in the maintenance of epidermal immune homeostasis. Furthermore, emerging evidence implicates epidermal TRM cells in a variety of human diseases, including HIV infection, fixed drug eruption, vitiligo, and alopecia areata. Collectively, these findings support a model in which conventional TRM cells, regulatory TRM cells, Langerhans cells, and keratinocytes form an integrated epidermal immune ecosystem that balances immune surveillance and immune regulation. Recognition of this cellular network challenges the traditional dermis-centric view of cutaneous immunity and suggests that the epidermis should be regarded as an autonomous immunological compartment. A deeper understanding of epidermal immune organization may provide new insights into the pathogenesis and treatment of epidermis-centered diseases.

Fixed drug eruption is a distinctive cutaneous adverse drug reaction characterised by the recurrence of well-demarcated lesions at the same anatomical site following re-exposure to the offending drug, with residual hyperpigmentation after resolution. Antimicrobials are common triggers, although fluoroquinolones are less frequently implicated. A man in his 30s developed multiple well-defined hyperpigmented patches involving the upper lip, upper limbs and foot within 24 hours of receiving levofloxacin for a lower respiratory tract infection. The lesions were pruritic, non-tender and recurrent at previously affected sites. Clinical findings and a clear temporal relationship supported the diagnosis of fixed drug eruption. Withdrawal of levofloxacin and symptomatic treatment resulted in gradual resolution with post-inflammatory hyperpigmentation. Causality assessment using the Naranjo scale suggested a probable association. This case highlights the importance of recognising fixed drug eruption caused by commonly prescribed antibiotics and the role of careful drug history taking and adverse drug reaction reporting.

Anaplastic lymphoma kinase (ALK) fusion genes are detected in approximately 3%-5% of non-small cell lung cancers (NSCLC). Alectinib and lorlatinib are ALK tyrosine kinase inhibitors with established efficacy; however, their adverse event profiles differ. We report a 61-year-old man with recurrent ALK-positive lung adenocarcinoma who developed a grade 2 drug eruption consistent with fixed drug eruption during alectinib therapy. The rash resolved following drug discontinuation and corticosteroid treatment. Lorlatinib was subsequently initiated without recurrence of cutaneous toxicity. Apart from Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 dyslipidemia, no significant adverse events occurred, and partial response has been maintained for over 1 year. This case suggests that lorlatinib may be a feasible alternative in patients who develop cutaneous adverse reactions to alectinib, enabling continuation of targeted therapy.

Acute vulvar mucocutaneous reactions during fluoropyrimidine-based chemotherapy are extremely rare. We describe the case of a 53-year-old woman diagnosed with stage IIA rectal adenocarcinoma undergoing neoadjuvant modified FOLFOX-6 (mFOLFOX-6) chemotherapy who developed an acute vulvar mucocutaneous reaction after one cycle of chemotherapy. Treatment was initiated with low-potency topical steroid cream without resolution and progressive pain requiring treatment intensification with high-potency topical steroid cream, topical lidocaine, and topical vaginal estradiol. Given the temporal association with chemotherapy and clinical features suggestive of a drug-related mucocutaneous reaction, possibly consistent with fixed drug eruption, the 5-fluorouracil (5-FU) bolus was omitted from subsequent cycles, allowing completion of all rounds of planned neoadjuvant chemotherapy without recurrence. This case expands the spectrum of known mucocutaneous toxicities associated with fluoropyrimidine-based chemotherapy and demonstrates that the omission of the 5-FU bolus preserves treatment efficacy while preventing the recurrence of this rare toxicity.