Tert-butylhydroquinone and tert-butylcatechol positivity as warning lights of skin sensitization to tert-butylphenol derivatives in adhesives and diabetes devices.

INTRODUCTION: Tert-butylphenol (TBP) derivatives, antioxidants in adhesives and diabetes devices, may provoke allergic contact dermatitis (ACD). OBJECTIVES: The objective of this study is to report sensitization to TBP derivatives in medical devices and to highlight that tert-butylhydroquinone (BHQ) and tert-butylcatechol (TBC) are potential screeners in this regard. METHODS: Fifteen patients with ACD from adhesives and diabetes devices were patch tested to different TBPs: BHQ 1% pet., TBC 0.25% pet., BHA 2% pet., BHT 2% pet., 4-tert-butylphenol (TBP) 1% pet. and 2,4-di-tert-butylphenol (di TBP) 1% pet. The culprit devices (medical adhesives, sanitary pads, diabetes devices) and TBP patch preparations were analysed using gas chromatography-mass spectrometry (GC-MS). RESULTS: BHQ (9/13), TBC (7/13), and to a lesser extent BHT (3/15), BHA (2/15) and TBP (2/13) gave positive reactions. Seven patients had developed ACD from adhesives and diabetes devices, respectively, and one patient from sanitary pads. GC-MS analyses of the medical devices and patch test materials confirmed the presence of the patch-test positive TBPs, or chemically related derivatives, or, interestingly, tert-butylbenzoquinones (BBQ) were found, that is, spontaneously formed, highly reactive TBP metabolites, likely (pseudo-) cross reacting with the patch tested TBPs. CONCLUSION: TBPs might be overlooked sensitizers in medical devices, and BHQ and TBC are potential screeners in this regard.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high-quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis.

Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis.

Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation.

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.

Unraveling the Immune Signature of Herpes Zoster: Insights Into the Pathophysiology and Human Leukocyte Antigen Risk Profile.

The varicella-zoster virus (VZV) infects >95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and individuals who are immunocompromised. However, HZ can occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in patients with HZ using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ human leukocyte antigen association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the major histocompatibility complex locus for HZ development, identifying 5 protective and 4 risk human leukocyte antigen alleles. This demonstrates that HZ susceptibility is largely governed by variations in the major histocompatibility complex. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation.

It is not always chlorhexidine: Identification of benzoxonium chloride and lauramine oxide as culprit allergens in a popular antiseptic in Switzerland.

BACKGROUND: A popular antiseptic spray in Switzerland (Merfen spray), containing chlorhexidine digluconate, benzoxonium chloride and lauramine oxide, is frequently used to treat skin wounds. However, it is also increasingly reported as a major cause of adverse skin reactions, including allergic contact dermatitis (ACD). OBJECTIVES: To investigate the contact allergens responsible for ACD from this antiseptic. PATIENTS/METHODS: Patch tests were performed on seven patients with a clinical history compatible with contact dermatitis from this antiseptic mixture. RESULTS: All patients presented with acute eczematous reactions following contact with either Merfen spray alone, or with multiple products including this spray. Patients showed positive reactions to this product in both patch tests and repeated open application tests (ROATs). Four patients showed dose-dependent reactions to both benzoxonium chloride and lauramine oxide. One patient showed a dose-dependent reaction to the former and a non-dose-dependent reaction to the latter. Finally, two subjects showed responses only to lauramine oxide. One patient reacted to chlorhexidine digluconate 0.5% aq. in addition to both other allergens. CONCLUSIONS: Two commercially unavailable allergens, that is, benzoxonium chloride and/or lauramine oxide were identified as major causes of ACD from Merfen antiseptic spray, whereas chlorhexidine digluconate was a contributing culprit in only one patient.

The European baseline series and recommended additions: 2023.

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.