The aim of the study was to report a case of bromfenac with sodium bisulfite preservative induced contact dermatitis and a secondary sterile corneal ring infiltrate. A 44-year-old male presented with a 1-week unilateral periocular dermatitis and eye redness. Initially the dermatitis responded to oral prednisone 80 mg and subsequent taper over 2 weeks. Upon tapering the prednisone, the patient returned with a recurrent dermatitis a week later. Dermatological workup included a skin biopsy demonstrating spongiotic dermatitis and a skin panel allergy test positive for sodium metabisulfite. The patient later mentioned self-administering bromfenac ophthalmic eye drops that contained sodium bisulfite. After the prolonged bromfenac use, the patient also developed a sterile corneal ring ulcer. The dermatitis finally resolved after discontinuing the bromfenac ophthalmic drops; however, the ring ulcer persisted after 3 months. Topical bromfenac ophthalmic drops may induce a severe contact dermatitis related to the inactive ingredient sodium bisulfite within the solution. Chronic use of the bromfenac may also cause a sterile ring infiltrate. Caution should be given to patients in using eye drops with sulfite sensitivity or allergy.
The long-term risk of allergic contact dermatitis (ACD) in children with atopic disease is a matter of debate. The study aimed to assess the long-term risk of patients with childhood-onset atopic asthma and/or rhinitis (AtRD), with and without childhood-onset atopic dermatitis (CoAD), to develop ACD in adulthood. A prospective cohort study with 15-year follow-up was conducted on 620 consecutive young adult patients (age 18-25 years) with childhood-onset AtRD (before the age of 16), and 173 healthy control subjects. All participants underwent skin prick tests for inhalant and food allergens. Patients were assigned to 2 cohorts. The NAD cohort included 483 patients with AtRD who had never had signs of atopic dermatitis. The AD cohort included 137 patients who, in addition to AtRD, had a presence or previous history of CoAD (onset within the first 5 years of life). Patients who showed clinical suspicion of contact dermatitis during follow up performed a patch test with a panel of 40 contact allergens. Those who tested positive for at least one contact allergen were considered to have contact allergy (CA). Patients with CA in whom the positive patch test had clinical relevance, assessed through detailed exposure analysis, were considered to be suffering from ACD. At the end of follow-up, the proportions of patients with CA (77.4% [106 of 137 patients] vs. 20.7% [100 of 483 patients]; p < 0.001) and patients suffering from ACD (52.6% [72 of 137 patients] vs. 14.7% [71 of 483 patients]; p < 0.001) were higher in the AD cohort than in the NAD cohort. In both cohorts, CA and ACD rates were higher than in control subjects (5.2% [9 of 173] controls; p < 0.001 and 1.7% [3 of 173 controls]; p < 0.001). In the overall group of participants, the multivariate Cox proportional hazards regression model showed that ACD was positively associated with AtRD (hazard ratio 1.67, 95% CI, 1.21-2.28, p = 0.001) and CoAD (hazard ratio 7.40, 95% CI, 5.74-9.52, p < 0.001) but not with IgE-mediated food allergy. In the AD cohort, the proportion of ACD did not differ between patients who had healed AD and those whose disease persisted into adulthood (49.2% [32 of 65 patients] vs. 55.5% [40 of 72 patients]), and the relative risk of ACD did not differ significantly between the two groups. Patients with childhood atopic asthma and/or rhinitis are exposed to an increased risk of ACD up to the fourth decade of life. The risk is independent of CoAD, even though the presence or past history of CoAD further increases the occurrence of ACD, regardless of whether patients have healed CoAD or not.
Recently, clonidine has been increasingly utilized for the treatment of tic disorders in children rather than for hypertension in adults. The transdermal patch is a common route of administration. Allergic contact dermatitis caused by clonidine transdermal patch was reported in adults with hypertension but never in children with tic disorder. We report on the first pediatric case developed allergic contact dermatitis within one to two weeks after using clonidine transdermal patch. Patch test with clonidine and Chinese baseline series including adhesive components (ethyl acrylate, methyl methacrylate, and 2-hydroxyethyl methacrylate) from the adhesive layer of the transdermal patch were performed. We report the first pediatric case with allergic contact dermatitis due to clonidine transdermal patch confirmed by patch test. She presented with pruritic erythema, blistering, and rupture at the patch site, matching its size and shape. Patch test with clonidine hydrochloride elicited positive reactions (++ to +++), while tests for specific components from the adhesive layer, including ethyl acrylate, methyl methacrylate, and 2-hydroxyethyl methacrylate, were negative, thereby identifying clonidine as the primary allergen. This case highlights that although clonidine itself has weak sensitizing potential, the transdermal therapeutic system may increase the risk of clonidine-induced sensitization and make it become a potential trigger for allergic contact dermatitis in clonidine transdermal patch users.
The present guideline updates the initial ESCD patch testing guideline, summarizing all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by highlighted short practical recommendations, which have been consensualized in a Delphi process. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
Allergic contact dermatitis (ACD) is an inflammatory skin disease triggered by allergen exposure. Entagenic acid (EA) is the main triterpene aglycone isolated from Entada phaseoloides, which has been documented to treat dermatitis, exhibits anti-inflammatory properties. However, its molecular mechanism in ACD remains unexplored. This study aimed to investigate the therapeutic effect of EA against ACD and explore its underlying molecular target and mechanism. The therapeutic effect of EA on ACD was evaluated in TNF-α/IFN-γ-stimulated keratinocytes and Squaric acid dibutylester (SADBE)-induced ACD mouse models. Integrated approaches including DrugBAN, GraphDTA, and thermal proteome profiling identified Activating Signal Cointegrator 1 Complex Subunit 2 (ASCC2) as the direct target of EA, which was confirmed by CETSA and ITC. The mechanism of EA targeting ASCC2 to alleviate keratinocytes inflammation was elucidated through transcriptomics, co-immunoprecipitation, and RNA interference. In vivo, intradermal injection of rAAV.DJ-CMV-ASCC2 was used to verify the ASCC2-dependent therapeutic effect of EA in ACD mice. Our study revealed that EA suppressed the expression of CXCL10 and CCL2 in keratinocytes and alleviated ACD-like symptoms in mice. EA decreased the mRNA levels of chemokines and regulated the NF-κB pathway through interrupting the interaction between ASCC2 and p65 in keratinocytes. In vivo, we also demonstrated that the overexpression of ASCC2 on skin of ACD mice reduced the EA-induced therapeutic effect. Our findings demonstrate that EA directly binds to ASCC2, attenuates NF-κB pathway transactivation, reduces key chemokine expression, and suppresses ACD-like progression, highlighting its potential as a therapeutic candidate for ACD.
Treatment of irritant contact dermatitis (ICD) is limited by the stratum corneum barrier, which hinders drug delivery and bioavailability. Sulforaphane (SFN) offers anti-inflammatory potential but suffers from poor stability and a short half-life. To address this, we developed a chitosan methacrylate (CSMA) hydrogel microneedle (MN) patch loaded with SFN-chitosan nanoparticles (SFN-CSNPs) for enhanced transdermal delivery.Network pharmacology identified 33 potential ICD-related targets of SFN, including SRC, EGFR, and JAK2, implicating pathways such as AGE-RAGE and Relaxin signaling. SFN-CSNPs were optimized via a Box-Behnken design, yielding nanoparticles with a size of 180-220 nm, PDI < 0.3, a Zeta potential of ∼ 24 mV, and a high encapsulation efficiency (91.94 ± 1.22%). These were incorporated into CSMA MNs using micromolding. The MN arrays exhibited robust mechanical strength (1.53 N/needle), enabling effective stratum corneum penetration. In vitro, the system achieved sustained release (183.6 ± 2.1 µg/cm2 over 60 h) and 11-fold higher skin retention than the SFN solution. It also demonstrated excellent stability, retaining > 85% drug content after 30 days at 4 °C. In an ICD mouse model, SFN-CSNPs@CSMA MNs significantly reduced erythema, edema, and epidermal thickening (45.37 ± 2.86 µm), approaching normal levels (20.03 ± 3.20 µm), and outperformed both SFN-CSNPs solution and dexamethasone ointment. This nano-MN platform effectively overcomes skin barriers, enhances drug stability, and enables localized, sustained release, offering a promising strategy for delivering unstable natural compounds such as SFN to treat inflammatory skin diseases.
Objective To elucidate the potential molecular mechanism of baicalein in the treatment of allergic contact dermatitis (ACD). Methods An in vitro inflammatory model was established using human keratinocytes (HaCaT cells) stimulated with tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The regulatory effect of baicalein on inflammatory factors was detected by quantitative real time polymerase chain reaction. Network pharmacology was applied to screen the common targets of baicalein and ACD. Key signaling pathways were predicted via a protein protein interaction (PPI) network and pathway enrichment analysis, and the binding capacity of baicalein to core targets was evaluated by molecular docking. Results In vitro experiments showed that baicalein significantly reduced the expression of pro-inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, but had no significant effect on the T helper 1 (Th1)/T helper 17(Th17)cell imbalance, suggesting that its anti inflammatory mechanism was not completely dependent on inflammatory pathways such as T cell activation and Th17 differentiation. A total of 46 potential targets of baicalein for ACD were screened by network pharmacology, and the functional enrichment was associated with inflammatory pathways including T cell activation and Th17 differentiation. Furthermore, 11 core targets were obtained from the 46 potential targets using CytoHubba and MCODE algorithms. Molecular docking results demonstrated that baicalein exhibited high binding affinity to core targets related to the cytochrome P450 (CYP450) family, among which the affinity with CYP1A1 was the highest (binding energy=-10.17 kcal.mol-1, RMSD=1.14 ). Conclusion Baicalein exhibits significant therapeutic potential against ACD. It can downregulate the expression of inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, and its mechanism may be related to the interactions with CYP450 family-related targets.
Cobalt is a well-established cause of allergic contact dermatitis (ACD), but data on the skin absorption, toxicity, and immunological effects of cobalt nanoparticles (CoNPs) remain limited. Given the increasing use of nanomaterials in industry and medicine, understanding how cobalt speciation affects skin immune activation is of growing clinical relevance. Fourteen cobalt-allergic individuals underwent standardized patch testing with cobalt chloride (CoCl2) and CoNPs at equivalent nominal doses. Skin biopsies from positive reactions were analyzed by RNA sequencing to characterize immune and barrier-related pathways. Cobalt penetration and localization were further examined in reconstructed and ex vivo human skin models using inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-TOFMS imaging. Both CoCl2 and CoNPs elicited positive patch test reactions, although CoNP responses were delayed and milder. CoCl2 also demonstrated a clearer dose-dependent increase in clinical reactivity, whereas CoNP responses were comparatively stable across concentrations. Transcriptomic profiling revealed substantial overlap between exposures, with reaction strength emerging as the main determinant of gene expression changes. Increasing severity was associated with enrichment of interferon signaling, inflammatory response, apoptosis, cell cycle-related programs, and glycolysis in both exposures. Lipid metabolic pathways were significantly associated with reaction strength in CoCl2-exposed skin but not in CoNP-exposed samples. Direct comparison using a paired DESeq2 design identified 281 differentially expressed genes between CoCl2 and CoNP. Functional enrichment of these genes revealed distinct biological signatures between exposures, including upregulated interferon and antiviral pathways and downregulated epithelial differentiation programs in CoCl2 compared to CoNP. In complementary skin models, CoCl2 exhibited deeper penetration, higher trans-epidermal flux, and broader intracellular accumulation across epidermal and dermal cell populations, whereas CoNPs remained largely confined to the stratum corneum and adnexal structures. Cobalt-induced ACD is shaped by both reaction strength and cobalt speciation. While CoCl2 and CoNPs share a core interferon-driven inflammatory program that scales with clinical severity, ionic cobalt penetrates more deeply and preferentially engages interferon and antiviral pathways in dermal compartments, whereas CoNPs are retained more superficially and are associated with epithelial differentiation programs. These findings underscore the importance of chemical form, tissue penetration, bioavailability, and retention in determining immune responses and dermal hazard of cobalt and other metal nanomaterials.
Allergic contact dermatitis (ACD) to personal care products (PCPs) represents a significant and growing clinical challenge, with increasing use of diverse PCPs and their expanding range of ingredients. Common allergenic components include fragrances, botanicals, preservatives, surfactants, emollients, emulsifiers, vitamins, and ultraviolet (UV) filters. Patch testing remains the gold standard for diagnosing ACD and identifying causative allergens, but traditional panels often fail to capture emerging PCP-related allergens. This review highlights key established and emerging PCP allergens, such as limonene and linalool hydroperoxides, sodium benzoate, octocrylene, and benzophenone-4. Strategies are discussed to optimize diagnostic accuracy through targeted series and repeated open application tests. Patient education about PCP labeling is paramount when assisting patients with allergen avoidance. Clinicians must balance precise allergen identification with practical management knowledge to improve outcomes in PCP-related ACD.
Allergic contact dermatitis (ACD) is a common inflammatory skin condition characterized by cutaneous inflammation and pruritus. Purinergic 2X receptor 3 (P2X3) and transient receptor potential ankyrin 1 (TRPA1) are implicated in acute and chronic pruritus, but their interactions remain unclear. Sesamin has anti-inflammatory, antioxidant, and antitumor properties; however, its effectiveness in alleviating ACD and the underlying mechanism remain unknown. In this study, male C57BL/6 mice (20-25 g body weight) were used. Results showed that squaric acid dibutylester (SADBE) increased scratching behavior and upregulated P2X3, TRPA1, IL-1β, and TNF-α expression in the right trigeminal ganglion (TG). Intraperitoneal administration of sesamin attenuated these effects, reducing pruritic behavior and inflammation-related gene expression. Compared to the control group, the ACD model group showed significantly increased co-expression of Mas-related G protein-coupled receptor member A3 (MrgprA3) and P2X3. Transfection experiments in HEK293 cells demonstrated that P2X3 regulated TRPA1 channel activation by modulating intracellular calcium levels. These findings suggest that sesamin alleviates pruritus in ACD mice, likely through downregulation of P2X3 and suppression of P2X3-mediated intracellular calcium elevation. Furthermore, sesamin inhibited TRPA1 expression and reduced calcium levels in cells co-transfected with the TRPA1 plasmid. Thus, sesamin may attenuate activation and expression of the inflammatory receptor TRPA1 by inhibiting P2X3, highlighting its potential as an antipruritic agent for SADBE-induced ACD.
Allergic contact dermatitis (ACD) is a common inflammatory skin disorder characterized as a T cell-mediated delayed-type hypersensitivity reaction induced by cutaneous exposure to haptens. Its pathogenesis unfolds through three distinct phases: sensitization, elicitation, and resolution. During sensitization, hapten-modified proteins are processed by dendritic cells, particularly Langerhans cells and dermal dendritic cells, which migrate to lymph nodes to prime naive T cells. Pattern recognition receptors, including Toll-like receptors and the NLRP3 inflammasome, critically regulate this innate-adaptive interface. The elicitation phase involves hapten-specific Th1 and Th17 cells orchestrating inflammation through cytotoxicity and cytokine release. Conversely, resolution relies on regulatory T cells and IL-10 and TGF-beta signaling to restore tissue homeostasis. Emerging immunomodulators such as vitamin D exhibit dose-dependent regulatory effects potentially influenced by sex-specific factors and U-shaped associations. Despite significant advances, critical gaps persist regarding tissue-resident memory T cells and precise sensitization thresholds. Integrating immunology, neurobiology, and metabolomics may advance precision therapies targeting pathways like NLRP12 or ultraviolet-induced vitamin D synthesis. This review summarizes current progress in elucidating the immunopathogenesis of ACD and highlights emerging mechanisms that may support the development of more precise and effective therapeutic strategies.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Chronic exposure to topical corticosteroids (TCS) in patients with atopic dermatitis (AD) may increase the risk of allergic contact dermatitis (ACD), which can mimic flares of the underlying disease and remain underrecognized. To evaluate patterns of TCS sensitization in patients with AD compared with patients without AD, with particular emphasis on the diagnostic limitations of baseline patch testing and the effect of test vehicle on allergen detection. In this prospective study conducted between September 2023 and January 2024, 80 patients with AD and 80 patients without AD underwent patch testing. The corticosteroid markers included in the Polish Baseline Series were budesonide 0.01% pet. and tixocortol pivalate 0.1% pet. The extended corticosteroid panel additionally included clobetasol-17-propionate 1.0% pet. and hydrocortisone-17-butyrate 1.0%, tested in petrolatum (pet.) and ethanol (alc.). Patch test readings were performed at 48, 72 h, and Day 7. Sensitization to hydrocortisone-17-butyrate was significantly more frequent in patients with AD than in patients without AD (23.8% vs. 8.8%; p = 0.018; OR 3.25, 95% CI 1.28-8.25). Positive reactions occurred exclusively to hydrocortisone-17-butyrate 1.0% in ethanol, whereas hydrocortisone-17-butyrate 1.0% in petrolatum was negative in all tested subjects. No positive reactions were observed to budesonide or tixocortol pivalate. Sensitization to clobetasol-17-propionate was uncommon and observed only in adults. Most reactions were first clearly detectable at 72 h or increased in intensity between 48 and 72 h, and one paediatric patient with AD had a delayed positive reaction detectable only on Day 7. The Polish Baseline Series alone may fail to detect some potentially clinically relevant TCS sensitizations in selected patients with AD. Extended corticosteroid testing, attention to the test vehicle, and Day 7 readings may improve case detection in selected clinical scenarios, particularly in patients with persistent or apparently treatment-refractory AD.
暂无摘要（点击查看详情）