Contact allergy to neomycin in consecutively patch tested Danish eczema patients from 2000 to 2023: A cross-sectional study.

BACKGROUND: Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines. OBJECTIVES: To identify time trends in contact allergy to neomycin in the period from 2000 to 2023. METHODS: A cross-section study of patients ≥18 years consecutively patch-tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000-2023 was conducted. RESULTS: The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period '2010-2023' (1.2%) than in '2000-2009' (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA-index) were identified when comparing neomycin contact allergic-patients in the two periods '2010-2023' and '2001-2009'. CONCLUSION: Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009.

Hippo/YAP signaling pathway protects against neomycin-induced hair cell damage in the mouse cochlea.

The Hippo/Yes-associated protein (YAP) signaling pathway has been shown to be able to maintain organ size and homeostasis by regulating cell proliferation, differentiation, and apoptosis. The abuse of aminoglycosides is one of the main causes of sensorineural hearing loss (SSNHL). However, the role of the Hippo/YAP signaling pathway in cochlear hair cell (HC) damage protection in the auditory field is still unclear. In this study, we used the YAP agonist XMU-MP-1 (XMU) and the inhibitor Verteporfin (VP) to regulate the Hippo/YAP signaling pathway in vitro. We showed that YAP overexpression reduced neomycin-induced HC loss, while downregulated YAP expression increased HC vulnerability after neomycin exposure in vitro. We next found that activation of YAP expression inhibited C-Abl-mediated cell apoptosis, which led to reduced HC loss. Many previous studies have reported that the level of reactive oxygen species (ROS) is significantly increased in cochlear HCs after neomycin exposure. In our study, we also found that YAP overexpression significantly decreased ROS accumulation, while downregulation of YAP expression increased ROS accumulation. In summary, our results demonstrate that the Hippo/YAP signaling pathway plays an important role in reducing HC injury and maintaining auditory function after aminoglycoside exposure. YAP overexpression could protect against neomycin-induced HC loss by inhibiting C-Abl-mediated cell apoptosis and decreasing ROS accumulation, suggesting that YAP could be a novel therapeutic target for aminoglycosides-induced sensorineural hearing loss in the clinic.

Combination of available topical beta-blockers and antibiotic ointment for epidermal growth factor receptor tyrosine kinase inhibitor-induced paronychia and pseudopyogenic granulomas in Taiwan.

BACKGROUND: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. METHODS: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin®) using the occlusion method to treat paronychia or PG. RESULTS: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. CONCLUSION: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.

Salvianolic acid B inhibits ototoxic drug-induced ototoxicity by suppression of the mitochondrial apoptosis pathway.

It has been claimed that salvianolic acid B (Sal B), a natural bioactive antioxidant, exerts protective effects in various types of cells. This study aims to evaluate the antioxidant and anti-apoptosis effects of Sal B in a cultured HEI-OC1 cell line and in transgenic zebrafish (Brn3C: EGFP). A CCK-8 assay, Annexin V Apoptosis Detection Kit, TUNEL and caspase-3/7 staining, respectively, examined apoptosis and cell viability. The levels of reactive oxygen species (ROS) were evaluated by CellROX and MitoSOX Red staining. JC-1 staining was employed to detect the mitochondrial membrane potential (ΔΨm). Western blotting was used to assess expressions of Bax and Bcl-2. The expression pattern of p-PI3K and p-Akt was determined by immunofluorescent staining. We found that Sal B protected against neomycin- and cisplatin-induced apoptotic features, enhanced cell viability and accompanied with decreased caspase-3 activity in the HEI-OC1 cells. Supplementary experiments determined that Sal B reduced ROS production (increased ΔΨm), promoted Bcl-2 expression and down-regulated the expression of Bax, as well as activated PI3K/AKT signalling pathways in neomycin- and cisplatin-injured HEI-OC1 cells. Moreover, Sal B markedly decreased the TUNEL signal and protected against neomycin- and cisplatin-induced neuromast HC loss in the transgenic zebrafish. These results unravel a novel role for Sal B as an otoprotective agent against ototoxic drug-induced HC apoptosis, offering a potential use in the treatment of hearing loss.

Effect of Topical Periocular Steroid Use on Intraocular Pressure: A Retrospective Analysis.

PURPOSE: To study the effect of periocular steroid use on intraocular pressure (IOP). METHODS: Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. RESULTS: Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1-83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of <1 mm Hg. One patient had a clinically significant intermediate steroid response of 7 mm Hg. CONCLUSIONS: Periocular steroid treatment causes a statistically significant rise in IOP in eyes with higher baseline IOP measurements, the risk of which increases with follow up. While this change is not always correlated with a clinically significant rise in IOP, clinicians should monitor more closely patients at greatest risk of steroid response.

Punctal stenosis in 6 dogs following the long-term use of topical neomycin-polymyxin B-dexamethasone.

Six dogs were diagnosed with punctal stenosis following the long-term use of topical neomycin-polymyxin B-dexamethasone (NPD). All patients were initially presented for ophthalmic diseases requiring ongoing anti-inflammatory therapy. Five of the 6 dogs had previously or concurrently been treated with topical anti-inflammatory medications other than NPD. One patient exclusively received topical NPD prior to the diagnosis of punctal stenosis. The onset of punctal stenosis following therapy with NPD was variable among patients, ranging from 4 months to over 1 year. Diagnosis of punctal stenosis was made based upon the presence of epiphora and visualization of fibrotic tissue over the nasolacrimal puncta.

Characterization of the Transcriptome of Hair Cell Regeneration in the Neonatal Mouse Utricle.

BACKGROUND/AIMS: Hearing and balance deficits are mainly caused by loss of sensory inner ear hair cells. The key signals that control hair cell regeneration are of great interest. However, the molecular events by which the cellular signals mediate hair cell regeneration in the mouse utricle are largely unknown. METHODS: In the present study, we investigated gene expression changes and related molecular pathways using RNA-seq and qRT-PCR in the newborn mouse utricle in response to neomycin-induced damage. RESULTS: There were 302 and 624 genes that were found to be up-regulated and down-regulated in neomycin-treated samples. GO and KEGG pathway analyses of these genes revealed many deregulated cellular components, molecular functions, biological processes and signaling pathways that may be related to hair cell development. More importantly, the differentially expressed genes included 9 transcription factors from the zf-C2H2 family, and eight of them were consistently down-regulated during hair cell damage and subsequent regeneration. CONCLUSION: Our results provide a valuable source for future studies and highlighted some promising genes, pathways or processes that may be useful for therapeutic applications.

Regional up-regulation of NOX2 contributes to the differential vulnerability of outer hair cells to neomycin.

In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics.

Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature.

A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

Melatonin mitigates neomycin-induced hair cell injury in zebrafish.

CONTEXT: Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides. OBJECTIVE: The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio). METHODS: Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 µM neomycin for 1 h. Surviving hair cells within four neuromasts were compared with that of a control group. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The changes of ultrastructure were confirmed using a scanning electron microscope. RESULTS: Melatonin alleviated neomycin-induced hair cell injury in neuromasts (neomycin + melatonin 100 µM: 13.88 ± 0.91 cells, neomycin only: 7.85 ± 0.90 cells; n = 10, p < 0.05) and reduced neomycin-induced apoptosis in the TUNEL assay. In ultrastructural analysis, hair cells within the neuromasts in zebrafish were preserved exposed to 125 µM neomycin and 100 µM melatonin for 1 h in SEM findings. CONCLUSION: Melatonin is effective in alleviating aminoglycoside-induced hair cell injury in zebrafish. The results of this study demonstrated that melatonin has the potential to reduce apoptosis induced by aminoglycosides in zebrafish.

Management of Hepatic Encephalopathy: A Primer.

OBJECTIVE: To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. DATA SOURCES: A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis All published articles evaluating treatments for HE were considered. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS: HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. CONCLUSION: Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Frequency and trends of contact allergy to and iatrogenic contact dermatitis caused by topical drugs over a 25-year period.

BACKGROUND: Allergic contact dermatitis is the most common adverse reaction caused by topical drugs. OBJECTIVES: To study the demographic characteristics and lesion locations of patients with iatrogenic dermatitis, and to analyse contact allergy to active principles and trends in frequencies over the years. PATIENTS AND METHODS: Between 1990 and 2014, 14 911 patients were patch tested with the European baseline series. Patients with a presumed iatrogenic cause were often tested with a pharmaceutical series, and, if indicated, with photo-patch tests. Most were also tested with the topical products to which they had been exposed, along with their ingredients. RESULTS: Eight thousand three hundred and seventy-four (56%) patients tested positively, and 2600 (17.4%, 95%CI: 16.8-18.0%) of all patients suffered from iatrogenic contact dermatitis. The most important primary sites of dermatitis were the legs, face, and hands. The most common sensitizers included topical antibiotics, antiseptics, and corticosteroids. The most frequent baseline allergens in this subgroup were budesonide, neomycin, and benzocaine, although with a decreasing trend over the years. Many other allergens from different pharmacological classes were identified. CONCLUSIONS: With a prevalence of 17.4% of consecutive patients, iatrogenic contact dermatitis is a frequent diagnosis in patients attending a general patch test clinic, involving one-third of the patients with at least one positive reaction.

Decreasing Rates of Neomycin Sensitization in Western Canada.

BACKGROUND: Neomycin contact sensitization rates in North America range from 7% to 13%, whereas in Europe they average approximately 1.9%. OBJECTIVES: Given that topical neomycin products are no longer readily available in Canada, the aim of this study was to examine what influence this may have had on neomycin sensitization rates in the 3 western provinces. METHODS: On the basis of an observation originally communicated by L. M. Parsons and C. Zhang of the University of Calgary, which suggested significantly reduced rates of neomycin sensitization in Calgary, Alberta, Canada, a multicenter study of patch test results from 5690 patient charts was undertaken. Data from 3 other western Canadian Universities (the University of Saskatchewan, the University of Alberta, and the University of British Colombia) were analyzed. Data were available from 2001 to 2013 for the University of Saskatchewan (except 2006), whereas the University of Alberta and the University of British Columbia had data from 2009 to 2013. Descriptive statistics, trend analysis, and risk estimates were determined using SPSS version 20. RESULTS: Sensitization rates for neomycin have decreased in western Canada and are now similar to those of Europe. CONCLUSIONS: This trend is likely influenced by the reduced availability of over-the-counter and prescription neomycin products in Canada.

Novel Hybrid Peptide Cecropin A (1-8)-LL37 (17-30) with Potential Antibacterial Activity.

Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed. C-L kills bacterial cells and causes disruption of surface structure, as determined by scanning electron microscopy. Synergistic effects were observed in the combination of C-L with several antibiotics (chloramphenicol, thiamphenicol, or neomycin sulfate) against Escherichia coli and Staphylococcus aureus.

Outcome of a second patch test reading of TRUE Tests® on D6/7.

Background. Two readings of patch test reactions are recommended. Objectives. To evaluate the outcome of a second patch test reading of TRUE Test® allergens on D6/7 in relation to negative or doubtful reactions on D3/4. Methods. This was a retrospective investigation of patch test data from January 1992 to October 2011 from consecutive eczema patients tested with the TRUE Test® panels. Results. In the period of nearly 20 years, a total of 9997 patients were tested. The total number of positive reactions to the 29 allergens was 6509; 4.4% were positive on D6/7 and negative on D3/4; and 9.1% were positive on D6/7 after a doubtful (?+) reaction on D3/4. Neomycin was the most frequent allergen giving delayed positive reactions (57%), followed by budesonide (42%) and hydrocortisone-17-butyrate (31%). Conclusion. A total of 4.4% of positive TRUE Test® reactions would be missed, and 9.1% might be missed, if only one reading was performed on D3/4. The results emphasize that many doubtful reactions at D3/4 may develop into positive reactions at a later reading. This may have important implications for evaluation of the clinical relevance of the test result.

Worsening of contact dermatitis by oral hydroxyzine: a case report.

Hydroxyzine is commonly used to treat pruritic skin lesions. Although rare, hydroxyzine can sometimes be linked to worsening dermatitis in patients who have sensitivities to phenothiazines and/or ethylenediamines. Herein we describe a patient who developed papulovesicular eruptions following the use of topical neomycin. Our patient's contact dermatitis initially improved after the use of oral steroids. However, the patient's skin condition was exacerbated by the continued use of hydroxyzine to treat her pruritus. Patch testing was positive at 48 hours for neomycin sulfate, ethylenediamine dihydrochloride, and p-phenylenediamine. Given the suspected cross-reactivity between hydroxyzine and ethylenediamine, hydroxyzine was discontinued and the patient's cutaneous symptoms improved. In summary, physicians must be aware that oral hydroxyzine can worsen contact dermatitis in ethylenediamine-sensitive patients.

Neomycin: sources of contact and sensitization evaluation in 1162 patients treated at a tertiary service.

BACKGROUND: Neomycin is used in several over-the-counter pharmaceutical formulations in Brazil. In Europe and Canada, where it is not freely available, its sensitization frequency is lower than in the United States, where this does not occur. OBJECTIVE: To present the frequency of sensitization to neomycin observed in a tertiary hospital and the pharmaceutical formulations sold in Brazil containing neomycin. METHOD: Retrospective analysis of positive results to neomycin, obtained through patch tests performed in a tertiary hospital, from 2009 to 2018 and investigation of topical drugs and vaccines containing neomycin in Brazilian databases available on the internet. RESULTS: Among 1,162 patients, 71 (6%) had positive reactions to neomycin, 65% female and 35% male individuals, 46% were over 50 years old, and 24% had a personal history of atopy. The dermatitis lasted from four months to 20 years. Lesions were located in 69% of the patients on the upper limbs, in 55% they were on the lower limbs, and in 42% they were disseminated in more than 4 sites. Polysensitization was detected in 55% of cases. Of these, 28% were linked to sensitization to rubber allergens and 27% to potassium bichromate. A total of 158 topical presentations of neomycin were found: 79 ointments, 58 creams, 10 ophthalmic solutions, seven otological solutions, one oral solution, two nasal solutions, and one antiseptic powder, in addition to 11 types of vaccines. STUDY LIMITATIONS: Retrospective study. CONCLUSION: Sensitization to neomycin occurred in 6% of the studied population, affecting more females aged over 50 years, with skin lesions located mainly on the upper and lower limbs, in the context of chronic contact dermatitis. Neomycin was found in 135 formulations, most of them available over the counter, as well as in 11 miscellaneous vaccines.