Anders Boutrup Funch

Background: Hairdressers are frequently exposed to shampoos, both from neat liquid products and dilutions, often with unprotected hands. Shampoos usually contain preservatives. While the level of preservation is guided by risk assessment based on typical consumer exposure, this will underestimate sensitization risk in hairdressers. Lower exposure or avoidance of preservative‐containing hair cosmetic products appears important for primary prevention of work‐related allergic contact dermatitis among hairdressers. Objectives: To assess the preservatives (Annex V of the EU Cosmetics Regulation (EC 1223/2009)) used in solid shampoos, compare these to preservatives present in liquid shampoos for professional use, and determine the presence of ingredients with “antimicrobial” function in solid shampoo. Methods: A physical store check and survey of online sales platforms was performed in four European countries in late 2024. Along with product descriptors, the full INCI labelling was recorded from package labels (or corresponding summaries online) and collected in a spreadsheet. Results: The sample included 172 solid shampoos from various retail sources and 259 liquid shampoos from one online marketplace for professional users. Among solid shampoos, preservatives were found in 31.4%; if “antimicrobial” additives are additionally considered, this share increased to 41.3%. Benzyl alcohol ( n = 29) and sodium benzoate ( n = 18) were the most common preservatives, benzyl benzoate the most common “antimicrobial” ( n = 8). By contrast, all liquid shampoos contained (multiple) preservatives. Conclusions: Solid shampoo shows potential to provide a less‐allergenic working environment for hairdressers. Practical aspects should next be addressed to contribute to broader use of solid shampoos.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by exposure of the skin to contact allergens. Classically, ACD is defined as a delayed-type (type IV) hypersensitivity reaction mediated by allergen-specific T cells, with symptoms peaking 48–72 h after exposure to the contact allergen. This delayed response to the contact allergen is seen during patch testing, where allergen-naïve, unaffected skin of allergic individuals is exposed to the contact allergen. However, in daily life and in certain occupational settings, allergic individuals often experience rapid flare-ups/exacerbations with intensely itching erythema, oedema, and often vesicles within hours after re-exposure to the specific contact allergen. These rapid flare-ups only develop at skin sites previously exposed to the contact allergen. Thus, it is important to distinguish between the rapid-onset reaction typically experienced by the allergic individual and the delayed-type reaction typically seen after patch testing. This review summarizes current insights into the immunopathology of rapid- versus delayed-type ACD reactions and outlines potential therapeutic opportunities, as well as their current limitations, against rapid-onset ACD, including modulation of cytokine signaling, T cell survival, checkpoint pathways, and redox balance.

Immunoglobulin G4 (IgG4), a unique subclass of IgG antibodies, plays diverse roles in human health and disease. Its distinct features, such as Fab-arm exchange and specific mutations, confer reduced effector functions compared to other IgG subclasses. In health, IgG4 responses contribute to immune tolerance, particularly in the context of allergen-specific immunotherapy (AIT), where they can mediate tolerance to environmental antigens, inhibit IgE-dependent mast cell degranulation, and compete with IgE for allergen binding. This helps in attenuating allergic symptoms and is associated with increased levels of allergen-specific IgG4. However, in disease scenarios, the role of IgG4 is complex. IgG4 lacks complement fixation and, thus, shows a reduced ability to activate immune effector pathways, it was initially thought to be protective against autoimmune diseases. However, emerging evidence suggests that it can contribute to pathology. For instance, IgG4 autoantibodies against specific antigens can aggravate conditions in certain autoimmune disorders. In some cancers, it may play a role in immune evasion, with higher levels correlating with poor patient survival, albeit in others, its exact function remains elusive. Overall, understanding the precise role of IgG4 in various physiological and pathological conditions is crucial for developing targeted therapeutic strategies and improving patient outcomes.

Background: Epidermal-resident memory CD8 ⁺ T (T _RM ) cells play a significant role in fighting off pathogens. However, CD8 ⁺ T _RM cells are also central in the pathogenesis of a variety of inflammatory skin diseases. It is unclear whether the generation and persistence of CD8 ⁺ T _RM cells are dependent on the presence of cognate antigen and T cell receptor (TCR) signaling. Methods: We determined the generation and persistence of epidermal CD8 ⁺ T _RM cells by flow cytometry and single-cell TCR sequencing in a well-characterized mouse model for allergic contact dermatitis. We examined the responses to four different contact allergens in combination with adoptive transfer and prime-pull experiments. We determined the presence of contact allergens in the skin by Western blot analysis. Results: We found that epidermal CD8 ⁺ T _RM cells can develop in the absence of the cognate antigen and TCR signaling as determined by Nur77 induction, whereas persistence of epidermal CD8 ⁺ T _RM cells requires presence of the cognate antigen and correlates with Nur77 expression. In the presence of contact allergen, a selective expansion of specific TCR clonotypes was seen. Conclusion: This study demonstrates that cognate antigen and TCR signaling are required for the persistence of allergen-specific CD8 ⁺ T _RM cells in the skin.

Background: Dysfunction of the skin barrier is regarded as a key event in the initiation and progression of inflammatory skin diseases. In many cases of allergic contact dermatitis (ACD), epidermal‐resident memory CD8 ⁺ T (T _RM ) cells play a central role in the immune response to contact allergens. However, if and how allergen‐specific CD8 ⁺ T _RM cells affect the expression of skin barrier molecules is not known. Methods: The expression level of skin barrier molecules was determined by RT‐qPCR and immunofluorescence in a mouse model of ACD. The role of CD8 ⁺ T cells on the expression of skin barrier molecules was investigated by depletion of CD8 ⁺ cells. Human primary keratinocytes were used to assess the direct effect of IFN‐γ and contact allergen on their expression of skin barrier molecules. Results: Sensitization with the contact allergen 1‐fluoro‐2,4‐dinitrobenzene (DNFB) resulted in epidermal accumulation of CD8 ⁺ T _RM cells and prolonged upregulation of Ifng and downregulation of keratin 5 ( Krt5 ) and Krt14 even after complete macroscopic remission of the inflammatory response. Challenge with DNFB lead to an additionally rapid downregulation of Krt5 and Krt14 and the downregulation of several other skin barrier molecules. Depletion of CD8 ⁺ cells abolished both the prolonged and rapid downregulation of skin barrier molecules. In keratinocytes, IFN‐γ and contact allergen synergistically down‐regulated the expression of KRT5 and KRT14. Conclusion: CD8 ⁺ T _RM cells contribute to a prolonged reduction in the expression of skin barrier molecules, which might exacerbate allergen permeation and the inflammatory response during succeeding exposures of the skin to allergens and antigens.

Background: Rubber accelerators are used in the vulcanization of rubber. However, rubber accelerators for example tetraethylthiuram disulfide (TETD) and zinc diethyldithiocarbamate (ZDEC) may cause contact allergy. Concomitant reactions between ZDEC and TETD have been observed in patients which could be explained by co‐ or cross‐reactivity.Objectives: To investigate cross‐reactivity between TETD and ZDEC and vice versa.Methods: Groups of mice were sensitized with TETD or ZDEC based on reported EC3‐values. Proliferation of lymphocytes were measured on day 5. To test cross‐reactivity, mice were sensitized and challenged 3 weeks later with TETD or ZDEC. The inflammatory response was measured by changes in ear thickness and the proliferative response in CD4⁺ and CD8⁺ T cells in the submandibular and cervical draining lymph nodes.Results: Sensitization of mice with doses of ZDEC 3%, TETD 5.6% or TETD 16.2% induced significant increased ear thickness and proliferation of CD4⁺ and CD8⁺ T cells. Challenge with ZDEC or TETD in these groups induced significant increased ear thickness. Challenge with ZDEC in mice sensitized to TETD 5.6% or TETD 16.2% induced significant increased proliferation of CD4⁺ and CD8⁺ T cells.Conclusions: We show cross‐reactivity between TETD and ZDEC. Patients sensitized to TETD or ZDEC should avoid exposure to both ZDEC and TETD.

Dear Editor, Allergic contact dermatitis (ACD) is a highly prevalent inflammatory skin disease affecting approximately 15% of the European population.¹ ACD is classified as a delayed-type hypersensitivity reaction mediated by ­allergen-specific memory T cells. The delayed nature of ACD is typically observed following patch testing of allergic patients where the patches are applied on the back of the patient. Using the back is both effective and practical due to the large surface area and because the skin of the back has typically not previously been exposed to contact allergens.² If the patient is allergic to the given allergen in a patch, a local eczematous skin lesion will typically appear within 2–7 days after the patch has been applied.^2,3 However, some patients develop dermatitis within a few hours after re-exposure of ACD healed skin to the contact allergen.^4,5 This form of rapid-onset ACD was first observed in animal experiments in 1963 and referred to as ‘rapid re-test reactions’.⁶ Subsequently, allergen-specific CD8⁺ skin-resident memory T (T_RM) cells have been shown to drive the rapid-onset ACD reactions as they persist over time locally within ACD healed skin.^5,7