When skincare backfires: The microbiome-stress-allergy axis in cosmetic hypersensitivity

Epidemiology

A 2025 meta-analysis comprising >4,000 children across 17 studies demonstrated that cosmetic contact allergy is prevalent in children globally, though positive patch test rates were comparatively lower in European populations than in those from the US, Asia, and the Middle East.^[11] Women are more susceptible to ACD, as they are more likely to be exposed to allergens in cosmetics and household products. Incidence rates are higher in urban populations than in rural ones, as a result of occupational and environmental factors. Cosmetic-related ACD accounts for a significant proportion of dermatology consultations, with fragrances, preservatives, and hair dye ingredients being among the most frequently implicated allergens. Studies report that women and professionals with repeated exposure to cosmetic agents, such as healthcare workers and hairdressers, form a substantial subset of these consultations, underscoring cosmetics as an important driver of contact allergy in clinical practice.^[12,13] Sensitization thresholds vary among individuals in the general population, and this suggests that while some people can withstand much higher doses of an allergen, others may develop contact allergies after being exposed to extremely low quantities.^[14] Epidemiological studies reported that 15% of individuals get allergic contact eczema annually, suggesting it has a high frequency and prevalence in populations of all ages. Teenagers had a point prevalence of 15.2% while adults showed 18.6%, which is significantly higher.^[15]

Skin microbiome and barrier function

The skin barrier is a complex system comprising physical, chemical, immune, and microbial barriers. The microbial barrier includes a diverse range of bacterial, fungal, and viral species that colonize the skin from birth and exhibit significant antimicrobial actions.^[16-19] Detergents can affect the skin’s epithelial barrier, leading to allergic diseases. They impair tight junction molecules of keratinocytes, increasing water loss and altering skin pH. This can lead to microbial dysbiosis, defined as an imbalance in microbiota, reducing microbial diversity and allowing allergens to penetrate, triggering inflammation leading to allergic diseases. Common handwashing, alcohol-based sanitizers, and antimicrobial soaps also compromise the microbial barrier. Studies found that topical commensal microbiota can help restore the skin’s microbial barrier.^[20,21] A study found that using acidic, 100% natural skincare formulations can significantly increase skin microbial diversity and improve barrier integrity, with the fastest improvement observed in the natural formulation group compared to synthetic product users, and this study reported no industry sponsorship.^[22] A study found that cosmetics can significantly alter the skin microbiota, leading to changes in skin hydration, reduced water loss, and increased bacterial diversity. Some positive effects include reducing acne risk, but the disruption of commensal skin microbiota, such as Staphylococcus and Corynebacterium raises concerns about unintended microbial balance disruption. In addition, prolonged mask usage has increased facial dermatoses (FD) such as CD and acne mechanica, particularly among healthcare personnel. Importantly, these conditions often overlap with cosmetic hypersensitivity, as compromised barrier function and occlusion from mask use may enhance penetration of cosmetic allergens and irritants, thereby exacerbating reactions to skincare and personal care products.^[23,24]

Active compounds and preservatives in cosmetics can alter skin flora by either disrupting beneficial commensals or exhibiting antimicrobial activity against harmful microbiomes. Preservatives such as parabens reduce microbial diversity and are linked with increased Staphylococcus aureus colonization, while methylisothiazolinone exerts strong antimicrobial effects that disrupt both harmful and commensal bacteria. Similarly, alcohols and surfactants decrease hydration and damage barrier lipids, impairing tight junctions and altering bacterial diversity. In contrast, barrier-enhancing compounds like ceramides support microbial diversity and improve barrier integrity.^[21] These ingredient-specific effects are summarized in Table 1. This highlights the connection between skin barrier function, microbial diversity, and cosmetic formulations, indicating that product composition is crucial in preventing or aggravating hypersensitive skin reactions.^[21]

Psychological stress and skin immunity

Stress affects the skin differently, with short-term stress enhancing immune protection and long-term stress linked to skin inflammatory conditions. Adrenocorticotropic hormone, corticotropin-releasing hormone, cortisol, and neuropeptides are among the hormones released in response to stress that impair skin barrier integrity, inhibit immune cell activity, and reduce the synthesis of antimicrobial peptides. These mediators increase the risk of infections and inflammatory conditions such as acne, psoriasis, and atopic dermatitis (AD). The local hypothalamus-pituitary-adrenal-like system, in which skin cells express these hormones, enables them to react to stress by sending immunomodulatory signals.^[25,26] As a result of adrenergic signaling, transforming growth factor β synthesis, fibroblast adipogenesis inhibition, and a decrease in cyclic adenosine monophosphate production, psychological stress increases skin susceptibility to S. aureus infection in murine studies.^[27] In a study comparing stressed and unstressed individuals, stress was associated with skin microbiome imbalance, reduced microbial diversity, and increased acidophilic and anaerobic bacteria contributing to skin disturbances characterized by lower skin pH, erythema, and blemishes.^[28] Stress is a major aggravating factor for acne, particularly in adult women with hormonal imbalances, and high stress levels have been positively correlated with acne severity through cortisol and androgen-mediated sebum overproduction, cytokine-driven inflammation, and barrier impairment.^[29-31] These same mechanisms, barrier breakdown, chronic inflammation, and immune dysregulation, also increase skin vulnerability to cosmetic allergens and irritants, thereby linking stress not only to acne but also to cosmetic hypersensitivity. In addition, stress-driven lifestyle changes such as poor sleep, altered diet, and intensified skincare routines may further amplify hypersensitivity reactions.^[32] Studies found that both acute and chronic stress were strongly linked with worsening of eczema symptoms. Stressful life factors such as family issues, financial issues, work overload, and examinations trigger psychological issues in students, leading to skin and hair-related problems like acne and sensitivity to cosmetics. Eczema also causes psychological distress, so addressing this aspect is crucial. Psychological interventions such as meditation, mindfulness, music therapy, massage therapy, and cognitive behavioral therapy are recommended.^[33-35]

Allergic responses to cosmetic ingredients

The increasing prevalence of allergic reactions to cosmetics in the past two decades highlights a global dermatological concern, demanding investigation into the immunological mechanisms and specific haptens, which are low molecular weight monomers responsible for these dermatoses.^[36] ACD is a type IV delayed hypersensitivity response, with a sensitization phase where an exogenous allergen, such as parabens, formaldehyde, and methylisothiazolinone, often found in cosmetics, penetrates the skin, forming an antigen complex with skin proteins and eliciting cytokine release, including interleukin-1 (IL-1) and tumor necrosis factor-α, followed by uptake by antigen-presenting cells (APC).^[12,37,38] APCs activate naive T-cells that ultimately differentiate into memory T-cells, which in the elicitation phase cause an inflammatory response approximately 72 h after the allergen reexposure through cytokines such as interferon-gamma, IL-2, and IL-17, resulting in the immune cell influx, which brings about the visible symptoms of ACD.^[6] In contrast to ACD, ICD lacks the sensitization phase and thereby has an immediate onset of dermatitis ranging from minutes to a few hours after exposure and is mainly an outcome of amplified innate immunity, rather than adaptive immunity. ICD is prompted by direct damage to the epidermal layer through the use of substances (such as cinnamon and cayenne pepper essential oils in lip plumper products), which disrupt the normal skin barrier function, producing an inflammatory response regulated by keratinocytes, fibroblasts, and other epidermal cells.^[39] Patch test studies have shown that cosmetic allergens are strongly associated with location-specific clinical manifestations. For instance, fragrance allergens such as linalool and limonene are linked to dermatitis (erythema, vesicles, and pruritus) on the face, neck, and flexural areas, while hair dyes (p-phenylenediamine [PPD]) predominantly affect the scalp, hairline, and eyelids. Nail resins often cause periungual eczema but can also spread to the eyelids through transfer. Likewise, benzophenones in sunscreens are associated with photoallergic dermatitis on photo-exposed areas, whereas nickel and cobalt from cosmetic tools or applicators commonly cause periocular or periorbital dermatitis.^[40] A summary of common cosmetic allergens, their predominant clinical sites, and presentation patterns based on patch testing is provided in Table 2.

Prominent pruritus and vesicles with ill-defined borders are the main symptoms in ACD, whereas burning and stinging sensations in a well-demarcated area are the chief complaint in ICD. Both conditions share overlapping features, including erythema, edema, and dryness.^[12] Table 3 summarizes the key clinical features and onset of ACD, ICD, and contact urticaria. Urticaria, a wheal and flare reaction – raised erythematous, itchy skin, usually observed immediately after exposure to chemicals such as thiomersal in eye make-up products, PPD in hair care products.^[41] Unlike ACD and ICD, contact urticaria can occur without previous sensitization or through an immunological type 1 hypersensitivity reaction leading to the degranulation of histamines from immunoglobulin E-mediated mast cells.^[42]

The allergens in cosmetics are generally classified based on their functions and are as follows:^[40]

• Fragrances

• Preservatives

• Hair dyes

• Sunscreens

• Conditioning agents

• Surfactants

• Excipients

• Nail product resins.

Fragrance allergens such as linalool and benzyl alcohol, in cosmetics for sensitive skin, have been found to be the leading cause of allergic reactions.^[3] Despite their growing use in cosmetic formulations, natural ingredients such as fruit extracts, like mango, have strong sensitizing effects.^[43] Methylisothiazolinone, found in skin care, hair care, and baby products, is the foremost preservative allergen in the nonformaldehyde-releasing preservative category, followed by parabens, which are identified in a multitude of products.^[40] Retrospective studies conducted through standardized patch tests reveal toluene-sulfonamide formaldehyde resin and PPD as one of the more common allergens, especially among women.^[44]

Microbiome-stress-allergy axis: Synergy and interplay

This triad, which is depicted in Figure 1, is relevant, especially in cosmetic hypersensitivity and AD, where dysregulated immune responses can worsen symptoms.^[45]

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Figure 1:

The microbiome-stress-allergy axis: Psychological stress (causes an increase in cortisol and neuropeptides) contributes to microbiome dysregulation marked by a decrease in beneficial commensals and an increase in harmful microbes, which in turn leads to immune dysfunction which includes T-helper cell 2 polarization, mast cell activation, and cytokine-mediated inflammation.

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Clinical manifestations and trends

Cosmetic hypersensitivity can often manifest as ACD.^[55] ACD can be acute and become chronic, especially if the allergen is not identified. It presents with erythema, blisters, pustules, crusts, scales, erosions, hemorrhage, and pain. Skin lesions in the areas of contact are characterized by asymmetric yet sharp-edged with symmetrical spread, developing in 24–48 h. compared to ICD, which has a rapid onset with no spreading.^[56,57] In addition, eczematous lesions with poorly defined erythema that affect the face, torso, and occasionally even on the exterior surface of the limbs are also characteristics of ACD.^[58] Whereas Riehl melanosis, another kind of ACD, manifests as either only pigmentation or pigmentation following erythema, edema, and pruritus, mostly presenting on the face, forehead, or zygomatic regions.^[59] Apart from this, ACD can also present itself as urticaria that mostly lasts as long as 24 h or less.^[60] Based on a retrospective study, terpene hydroperoxides like limonene and linalool hydroperoxides found in fragrances are major contributors to fragrance contact allergy, with 30.6% of patients developing cosmetic-induced FD as a result.^[56,61] Table 4 outlines agent-wise allergy patterns of cosmetic ingredients.

A community-based cross-sectional study from India involving 1,000 participants reported that 12.5% experienced cosmetic-related adverse events, most commonly acneiform eruptions (4.3%), CD (3.5%), and pigmentation changes (2.1%). Less frequent but notable reactions included conjunctivitis, photo-allergic/toxic responses, itching, and scalp damage. The authors emphasized that adverse effects often manifested after repeated product use and highlighted the importance of consumer awareness and dermatological consultation in early diagnosis and prevention.^[62]

Diagnosing ACD might be challenging due to its diverse clinical presentations. Therefore, prompt diagnosis and updated treatment are crucial to preventing adverse effects on a patient’s quality of life (QoL).^[60]

Risk factors

An experimental study using patch testing in 77 patients with facial dermatitis demonstrated that 27.4% had cosmetic-related facial ACD, with a female predominance of 9.1% and a mean age of 37.3 ± 14.8 years. The study identified positive patch test reactions to common cosmetic allergens, particularly fragrances and preservatives. Overall, 45.5% of patients were diagnosed with ACD, with key risk factors including female sex, prior history of cosmetic allergy, and occupational exposure such as the use of hairdressing products.^[63] According to studies, repeated exposure to allergens may also raise the risk of developing ACD in those with AD.^[64]

Prevention and management strategies

Adjunct pharmacologic therapy

Topically prescribed agents such as corticosteroids (TCS), calcineurin inhibitors, Janus kinase inhibitors, phosphodiesterase-4 inhibitors, and moisturizers are used in AD management. It was found that TCS group 1 was most efficacious in improving AD severity, TCS groups 2–5, and high-dose 0.1% topical tacrolimus, which were most efficient in improving itch severity, and delgocitinib was best suited for improving QoL in eczema. Least effective were topical antibiotics alone or combined with other topical treatments. Long-term maintenance was better seen with TCS group 5.^[72] Figure 2 summarizes the main strategies discussed.

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Figure 2:

Summary of prevention and management strategies for cosmetic hypersensitivity.

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Future directions

Advances in microbiome profiling methods, such as metagenomic shotgun sequencing and amplicon-based sequencing, are spurring demand for personalized skincare. The epidermal permeability barrier can be disrupted by stress, leading to dermatological conditions such as AD. Collaboration with mental health specialists may mitigate the detrimental effects of these conditions.^[73,74] Future diagnostic approaches for cosmetic hypersensitivity should explore reactive and personalized tools, potentially including mobile-based patch testing, wearable irritant sensors, or predictive algorithms to enable early detection and individualized risk assessment, aligning with broader trends in healthcare innovation.^[75] AI algorithms can predict ingredient sensitivity by analyzing chemical compositions for retinoids, parabens, and sulfates. Further cross-referencing with skin profiles, including allergy history, would enhance skincare personalization. Multiplex target detection using biosensors can detect and analyze microbiomes. AI-based applications like dermacompass can detect conditions like hand eczema and grade them based on severity. An interdisciplinary framework is needed to understand multifactorial causations and advance holistic diagnostic strategies.^[76-79]