Comprehensive Approaches to Diagnosis and Treatment of Sensitive Skin

Abstract

Sensitive skin (SS) is increasingly recognized as a complex syndrome characterized by discomfort and heightened sensitivity to otherwise harmless stimuli, such as environmental changes, physical contact, and cosmetic products. This condition poses challenges in both diagnosis and treatment due to its variable presentation and subjective nature. The pathophysiological features of SS include neurogenic inflammation and small fiber neuropathy, largely driven by the hyperactivation of sensory nerves. This hyperactivation is closely associated with transient receptor potential (TRP) channels, particularly TRPV1, which contribute to the exaggerated sensory responses seen in SS. Furthermore, psychological factors like stress and anxiety, along with environmental stressors such as pollution and ultraviolet exposure, play significant roles in exacerbating symptoms. The diverse and individualized responses to stimuli make it difficult to establish standardized diagnostic criteria for SS, necessitating a combination of subjective diagnostic tools (e.g., the Sensitive Scale-10) and objective assessments (e.g., transepidermal water loss and lactic acid sting test) to accurately identify and assess SS. This paper provides a comprehensive review of SS, covering its definition, prevalence, pathogenesis, diagnostic challenges, and management strategies, and highlights the importance of personalized care in effectively managing SS and improving patient quality of life.

INTRODUCTION

Sensitive skin (SS) is increasingly recognized as a complex syndrome marked by heightened and often painful sensory responses to typically innocuous stimuli, such as environmental changes, physical contact, or cosmetic products. This condition affects not only physical well-being but also significantly impacts patients’ mental health and quality of life, frequently causing distress and anxiety. The multifaceted nature of SS poses challenges in both diagnosis and treatment, primarily due to the subjective nature of its symptoms and the lack of universally observable clinical signs¹.

Recent advances in dermatological research underscore the role of neurogenic components in SS. Specifically, SS is now understood to involve neurogenic inflammation and may be associated with neuropathic characteristics similar to those observed in small-fiber neuropathy². Neurogenic inflammation in SS arises from the overactivity of sensory nerve fibers, particularly in relation to C-fibers, which are responsible for transmitting sensations of pain, heat, and itch. Additionally, transient receptor potential (TRP) channels, especially TRPV1, have been implicated in the exaggerated sensory responses of SS, linking this condition to an intrinsic hypersensitivity of sensory nerve endings in the skin³. Moreover, psychological and environmental stressors play a crucial role in exacerbating SS symptoms. Psychological factors, such as anxiety and stress, have been shown to lower the sensory threshold in SS patients, making them more susceptible to external triggers. Environmental factors, including pollution, ultraviolet (UV) exposure, and seasonal changes, are also well-established as aggravators of SS, contributing to the activation of sensory receptors and the initiation of neurogenic inflammatory pathways in the skin⁴. This interplay of neurogenic, psychological, and environmental factors highlights the importance of a comprehensive approach to understanding SS and underscores the need for personalized management strategies.

Therefore, this review aims to provide an in-depth examination of the definition, diagnostic challenges, and appropriate management techniques for SS. By integrating recent findings from neurobiology, psychodermatology, and environmental dermatology, this discussion will advance the understanding of SS as a distinct neurodermatological syndrome, necessitating an interdisciplinary approach in both research and clinical practice.

DEFINITION OF SS

SS is a complex syndrome that is characterized by hypersensitivity to stimuli, and is subjective and diverse depending on the individual’s age, gender, race, etc., and is difficult to diagnose and manage due to the absence of clinical signs⁴. Frosch and Kligman introduced the concept of skin sensitivity¹. In experiments involving lactic acid sensitivity tests on various skin areas, it was confirmed that skin sensitivity varies based on gender and race, with the face being the most common site.

Since 1987, SS has been termed ‘Cosmetic Intolerance Syndrome,’ denoting instances where discomfort arises upon cosmetic application⁵,⁶. The definition has progressively broadened to encompass sensations induced by factors beyond cosmetics⁷. It is now understood that SS can be triggered by various factors beyond cosmetics, including environmental stressors, temperature changes, hormonal fluctuations, and psychological stress⁸. These triggers, which vary widely across individuals, contribute to the difficulty in establishing a universal diagnostic criterion for SS.

In 2017, the International Forum for the Study of Itch (IFSI) redefined SS as a syndrome causing discomfort in response to typically non-irritating stimuli, often linked to specific skin diseases⁹. SS is acknowledged as a heterogeneous and complex syndrome lacking fully objective diagnostic criteria; while skin lesions may appear normal or present with erythema, symptoms are quantified through subjective assessment tools, such as the SS-10².

Meanwhile, in Fitzpatrick’s Dermatology, Dr. Bauman categorizes SS into 4 types: allergic type, rosacea type, acne type, and stinging type¹⁰. This supports the argument that SS itself is associated with chronic skin conditions on the face. In other words, when defining SS, cases where a specific skin condition exists as a current symptom should be excluded from the category of SS¹¹. This suggests that individuals with frequent abnormal skin sensations may be prone to certain skin conditions, making it essential to distinguish between symptoms of chronic skin conditions and those solely due to sensitivity¹².

In summary, SS is characterized by exaggerated responses to typically non-irritating stimuli, influenced by environmental, psychological, and genetic factors, with its complex and subjective nature necessitating ongoing revisions and personalized approaches for accurate definition and treatment.

EPIDEMIOLOGY OF SS

SS affects a significant portion of the global population, with prevalence estimates varying widely across studies. Survey-based studies indicate that approximately 50%–60% of women and 30%–40% of men are reported to have SS¹³. According to a 2019 meta-analysis, self-reported prevalence of SS varies by region due to survey methods and cultural perceptions, with 71% reporting some degree of SS and 40% reporting moderate to severe SS globally.

Gender and age differences affect SS prevalence, with women and younger individuals (especially under 35) reporting SS more often, likely due to hormonal factors, skin thickness, cosmetic usage, and generational awareness of sensitivity⁸. Environmental factors like pollution, humidity, UV exposure, and psychological stress exacerbate SS symptoms, especially in urban areas, by compromising the skin barrier and triggering inflammation, highlighting the complex factors influencing SS prevalence and severity¹⁴.

In summary, SS is a common but diverse condition influenced by both biological and environmental factors, requiring regionally and culturally tailored approaches to diagnosis and management.

CLINICAL SYMPTOMS OF SS

SS is characterized by subjective sensory symptoms like stinging, burning, and itching in response to benign stimuli, often without visible signs, making diagnosis challenging, and is influenced by external triggers (e.g., temperature, pollution, cosmetics) and internal factors like psychological stress. (Table 1)¹⁵,¹⁶. In Table 1, higher odds ratios (ORs) suggest stronger associations between specific triggers and the presence of SS. For example, cosmetics (OR, 7.12; 95% confidence interval, 3.98–12.72) represent the most significant trigger, indicating individuals exposed to cosmetics are over 7 times more likely to report SS symptoms compared to those not exposed.

Table 1. Triggers and ORs of sensitive skin according to meta-analysis¹⁰ .

Factor	OR	95% CI
Cosmetics	7.12	3.98–12.72
Wet air	3.83	2.48–5.91
Air conditioning	3.60	2.11–6.14
Temperature variation	3.53	2.69–4.63
Heat	3.50	2.56–4.77
Water	3.46	2.82–4.25
Pollution	3.18	2.37–4.27
Dry air	3.04	2.22–4.16
Cold	2.73	1.94–3.84
Wind	2.33	1.69–3.22
Sun	1.81	1.61–2.04
Emotion	1.77	1.44–2.17

OR: odds ratio, CI: confidence interval.

Site-specific and demographic variability in symptoms

SS most commonly affects the face, especially areas with thinner skin like the cheeks and forehead, with higher intensity in East Asian populations potentially due to genetic or structural facial skin differences¹⁷.

Gender and age also influence symptom severity and frequency

Women and younger individuals report SS more frequently, likely due to factors such as thinner skin, hormonal changes, cosmetic use, environmental stressors, and greater skincare awareness⁸.

Evaluating symptoms and severity

The SS-10 scale helps quantify SS severity by evaluating symptoms like stinging and burning over recent days, providing a standardized yet still subjective assessment of symptom intensity¹⁸,¹⁹.

PATHOPHYSIOLOGY OF SS

The pathophysiology of SS involves a multifaceted interaction among impaired barrier function, inflammatory responses, neurosensory dysregulation, and genetic predispositions Fig. 1. These factors collectively contribute to the heightened reactivity of SS, where otherwise benign stimuli provoke intense sensory symptoms. Each mechanism plays a crucial role in the development and persistence of SS symptoms⁴,²⁰,²¹.

Fig. 1. Schematic illustration of the pathophysiology of sensitive skin, including key mechanisms such as impaired barrier function, neurosensory dysregulation, inflammation, and genetic susceptibility.

GPCR: G protein-coupled receptor, TRP: transient receptor potential, KC: keratinocyte, DC: dendritic cell, NO: nitric oxide, ATP: adenosine triphosphate.

Impaired skin barrier function

The skin barrier, particularly the stratum corneum (SC), is crucial for protecting against external irritants and preventing transepidermal water loss (TEWL). SS is often associated with a thinner SC and increased TEWL¹,²², which allows for the penetration of irritants and allergens, exacerbating sensitivity to external stimuli. Our previous study also demonstrated a significant difference in TEWL between the sensitive and control groups²³. Studies have shown that individuals with SS have reduced levels of natural moisturizing factors and lipids such as ceramides, leading to decreased skin hydration and compromised barrier integrity²². Additionally, conditions like atopic dermatitis (AD), where the barrier function is already compromised, often overlap with SS, suggesting a synergistic effect between AD-induced barrier impairment and SS²⁴,²⁵,²⁶,²⁷. However, limited studies on the effect of barriers exist, and some investigations suggest no clear association between barrier conditions and SS²⁴,²⁶.

Inflammatory responses

Individuals with SS often show low-grade inflammation without visible signs, marked by elevated levels of pro-inflammatory cytokines like CCL17 and interferon-γ, sustaining mild skin inflammation.²⁸ This chronic inflammation sensitizes the skin to external triggers, further lowering the threshold for irritation and increasing reactivity to stimuli such as temperature changes and certain chemicals.

Neurosensory dysregulation

SS is considered a neurogenic disorder involving skin barrier and sensory nerve dysfunction, characterized by reduced C-fiber density and overstimulated TRP channels like TRPV1, which amplify sensory reactions and increase sensitivity²,²⁹.

Studies have shown that reduced intraepidermal nerve fiber density (IENFD) is linked to hyperesthesia in SS, resembling small fiber neuropathy³⁰,³¹. Reduced IENFD in SS patients supports this pattern, with research identifying a decreased number of peptidergic C-fibers in SS, likely contributing to heightened reactivity in the remaining nerve endings³². The overstimulation of nociceptive channels on these nerve endings by neuropeptides, such as calcitonin gene-related peptide (CGRP), may lead to neurogenic inflammation in the skin. Activation of these receptors often results in sensations like burning, tingling, and stinging, frequently reported by SS patients³³. Excessive CGRP release in SS overstimulates pain receptors via TRP channels, leading to neuropathic inflammation and sensitivity, mirroring features of small-fiber neuropathy like reduced nerve fiber density and abnormal heat-pain thresholds³⁰,³⁴,³⁵,³⁶,³⁷.

Recent studies suggest SS pathophysiology resembles neuropathic pruritus in small-fiber neuropathy, with a proposed condition called neurogenic rosacea exhibiting rosacea traits alongside neurological symptoms like burning and stinging, resistant to conventional therapies but partially responsive to anticonvulsants and antidepressants, supporting a neuropathic basis shared with SS³⁸. In a recent study, some SS patients displayed typical neurogenic symptoms, as confirmed through responses to the SS-10 questionnaire¹⁵. Von Frey Filament Test assessments reveal decreased mechanical pain thresholds in SS-affected areas, like the cheeks, suggesting peripheral sensory neuropathy as a key factor in SS pathogenesis, which is also linked to neuropathic disorders like irritable bowel syndrome and sensitive eyes³⁹.

Sensations in SS are influenced by nerve fibers as well as keratinocytes and other epidermal cells expressing sensory proteins like TRP channels. Overexpression of channels such as TRPV1 and ASIC3 in SS leads to calcium influx and neurogenic inflammation upon activation by stimuli like acidic pH, heat, and chemicals, explaining SS’s heightened sensitivity to environmental triggers⁴⁰.

Transcriptomic studies reveal reduced PIEZO2 mRNA levels in SS patients, suggesting PIEZO2 dysfunction may contribute to SS hypersensitivity. TRPV1 channels, involved in mechanotransduction in Merkel cells, further link to this sensitivity, as genetic deletion of Merkel cells induces allokinesis, highlighting the roles of both PIEZO2 and Merkel cells in SS pathophysiology⁴¹,⁴². Moreover, the dedicator of cytokinesis nine gene (DOCK9), which encodes a protein regulating dendrite growth, is downregulated in SS, correlating with decreased nerve fibers and increased sensitivity.

SS pathophysiology parallels that of complex regional pain syndrome (CRPS), a disorder involving peripheral sensory neuropathy. In CRPS, repeated exposure to irritants causes sensory nerve damage and neurogenic inflammation, leading to peripheral neuronal sensitization with lowered sensory thresholds and increased excitability through the activation of protein kinases A and C, which phosphorylate sensory-specific sodium channels⁴³. Over time, the desensitization of nociceptive neurons through phosphorylation of G-protein-coupled receptors and ion channels can gradually induce central sensitization, leading to persistent paresthesia.

Recent transcriptomic research shows that patients with SS exhibit upregulated genes associated with inflammatory pathways, revealing a complex interplay between skin barrier dysfunction and neuropathic pruritus²⁹. This dual neurological and dermatological dysfunction places SS within a spectrum of neuropathic skin disorders, similar to neuropathic pruritus.

Genetic and epigenetic contributions

Genetic factors may predispose individuals to SS, with variants in genes related to skin barrier proteins like filaggrin and neurosensory receptors like TRPV1, affecting skin structure and sensory perception and potentially explaining symptom variability across populations⁸. Additionally, environmental influences, including pollution and lifestyle factors, may cause epigenetic modifications that impact the skin barrier and neurosensory pathways, further contributing to SS.

DIAGNOSIS OF SS

Diagnosing SS presents unique challenges due to the subjective nature of its symptoms and the frequent lack of visible lesions. Patients often report abnormal sensations, such as stinging and burning, triggered by common external factors like temperature changes or cosmetic products. These sensations generally occur without any accompanying clinical signs, complicating the diagnostic process. Thus, a comprehensive diagnostic approach combining both subjective assessments and objective measurements is essential to accurately identify SS⁴⁴.

Subjective diagnostic tools

The SS-10 is a self-administered questionnaire consisting of 10 items, each rated on a scale from 0 (no symptom) to 10 (extreme symptom intensity), assessing common symptoms such as stinging, burning, and tightness experienced over the past 3 days. The total score ranges from 0 to 100. A score ≥20 is typically indicative of SS, while scores above 50 may represent severe cases requiring intensive management. A cutoff of 12.7 has shown 72.4% sensitivity and 90.3% specificity for SS diagnosis (Fig. 2). In SS research, an SS-10 score of 20 typically defines SS, with 50 indicating severe cases needing intensive treatment, while a cutoff of 12.7 has demonstrated 72.4% sensitivity and 90.3% specificity in distinguishing SS cases⁴⁵.

Fig. 2. The Sensitive Scale-10 (SS-10): a validated questionnaire developed by Misery et al.¹⁸ to quantify sensitive skin symptoms. It includes 10 items rated from 0–10, with a maximum score of 100.

Objective diagnostic tools

Although there are often no clinical signs, diagnostic tests such as the lactate challenge test (Lactic Acid Sting Test [LAST]) and the capsaicin test are used to assess skin sensitivity⁴⁴. Several methods exist to test SS, with the LAST being the most representative¹,¹¹. This test entails applying a 10% lactic acid solution to the nasolabial fold and cheek area, followed by rubbing the skin after 2 minutes 30 seconds, and 5 minutes to assess sensitivity⁴⁶. Patients scoring 3 or more out of 4 are classified as having SS, but due to inconsistent results in tests like the Lactic Acid Stinging Test, Sodium Lauryl Sulfate (SLS) Occlusion Test, and Capsaicin Test, SS is recognized as a heterogeneous group with limitations arising from subjective interpretation and result variability. Currently, there are subjective and objective methods employed in testing patients with SS, as perceived by the subjects in terms of skin irritation. Subjective measurement methods include tests that induce sensations such as stinging test using lactic acid¹ or eliciting a burning sensation with a mixture of chloroform and methanol⁴⁷. Objective tests involve applying surfactants like SLS⁴⁸ to measure erythema index and trans-epidermal water loss, as well as using dimethyl sulfoxide⁴⁹ to induce swelling and erythema, and exposing the skin to ammonium hydroxide solution⁵⁰ to measure blistering time.

Existing research has struggled to standardize and objectify measurement methods, with studies using the Hilltop chamber to apply 0.1% lactic acid to the malar area⁵¹. This method assesses the stinging sensation over 10 minutes by comparing the onset and peak intensity, with studies showing that increasing lactic acid concentration up to 10% raises stinging intensity, after which it plateaus, while earlier onset and additional symptoms like erythema and itching appear⁵¹. Another study reported that the LAST is the most effective method for distinguishing sensitive from non-SS based on a survey⁵². Tests like LAST, SLS occlusion, and capsaicin rely on subjective assessment or show inconsistent results, highlighting the heterogeneity of SS and the need for objective indicators. Recent diagnostic advancements include TEWL measurements and the ANTERA 3D^® system for quantitative evaluation of skin texture, redness, and hydration, used alongside clinical photography for long-term SS monitoring⁵³. TEWL measurement, in particular, has proven useful in correlating skin sensitivity with barrier function abnormalities, such as increased water loss and reduced hydration⁵⁴.

Combining diagnostic methods

Combining SS-10 with objective measures like TEWL or LAST offers a more reliable SS diagnosis, especially for complex cases, such as those with heightened sensitivity from prolonged mask usage during the coronavirus disease 2019 (COVID-19) pandemic.

Investigation into related skin diseases

When skin sensitivity is detected, further investigation into associated skin diseases is essential. Patch testing remains crucial for diagnosing irritant and allergic contact dermatitis in SS, identifying triggers like allergens or irritants, especially for patients whose symptoms worsen with specific skincare products⁵⁵ During COVID-19, patients reporting increased skin sensitivity from mask-wearing may have conditions like irritant or allergic contact dermatitis, folliculitis, seborrheic dermatitis, or worsened rosacea. Previous studies showed high sensitivity to fragrance mix 1 in SS patients through patch testing²³. Coexisting skin conditions like neurogenic rosacea and AD in SS patients are assessed through facial imaging, TEWL, blood tests, patch tests, and Demodex density tests, aiding in accurate treatment, identifying SS causes, and preventing recurrence.

MANAGEMENT OF SS

The treatment of SS requires a personalized approach due to the variability in symptoms and triggers across individuals (Fig. 3). Effective SS treatment plans should address underlying skin conditions, symptom duration, severity, and specific triggers, aiming to relieve sensations and visible issues while strengthening the skin barrier. Treatments should focus on barrier repair and neurosensory regulation, with gradual tapering of medication to avoid rebound symptoms, even if lesions are absent.

Fig. 3. Proposed stepwise management algorithm for sensitive skin. Emphasizes trigger avoidance, barrier repair, subjective/objective assessment, and personalized pharmacologic strategies.

TEWL: transepidermal water loss, GABA: gamma-aminobutyric acid.

Identification and avoidance of triggers

Effective SS management involves identifying and minimizing triggers through patient history and using patch tests to detect allergens. Patients with AD are advised to avoid fragrances and irritants due to their compromised skin barrier⁵⁶.

Emollients and barrier repair

Moisturization is key in SS treatment, but frequent changes in products can worsen sensitivity. Patients should test new products on the forearm Repeat Open Application Test for 2 weeks, and for recurring reactions, an “as-is” patch test can confirm compatibility. TEWL is a key indicator of barrier integrity and sensitivity; elevated TEWL suggests barrier dysfunction. Barrier-repair products, like ceramide moisturizers, enhance resilience, while anti-inflammatory emollients (e.g., with colloidal oatmeal or niacinamide) help reduce discomfort and support recovery⁵³,⁵⁴.

Pharmacologic options

If symptom relief through avoidance and barrier repair is insufficient, tailored pharmacologic treatments may be used. Antihistamines help with itching, beta-blockers reduce flushing, and serotonin-norepinephrine reuptake inhibitors and gamma-aminobutyric acid analogs (e.g., pregabalin, gabapentin) relieve SS symptoms by reducing sensitization and nociceptive signaling⁵⁷. Topical calcineurin inhibitors, like pimecrolimus and tacrolimus, help manage SS by reducing inflammation and neurosensory sensitivity without causing skin thinning, suitable for long-term use. Intradermal botulinum toxin injections also show promise by inhibiting neurotransmitter release and reducing pain.

Additional therapies: oxidative stress and neuromodulators

Oxidative stress worsens SS by weakening the skin barrier and increasing inflammation. Antioxidant treatments, such as topical vitamins C and E or resveratrol, help reduce oxidative damage and aid barrier recovery, supporting SS management. Emerging SS treatments include topical neuromodulators like capsaicin, which desensitizes TRPV1 channels to reduce burning and stinging, and cannabinoids, which may relieve inflammation and pain. Neuropathic pain management options like anticonvulsants and botulinum toxin also offer targeted relief for severe symptoms.

Comprehensive and personalized care

Managing SS requires a comprehensive, patient-centered approach that combines subjective (SS-10) and objective (TEWL, patch testing) assessments. Personalized plans including barrier repair, trigger avoidance, and tailored treatments improve outcomes, especially for patients affected by environmental triggers. Integrating new insights enhances treatment effectiveness, quality of life, and reduces symptom recurrence.

CONCLUSION

SS is a complex and multifaceted condition influenced by diverse physiological, environmental, and genetic factors. This syndrome, characterized by heightened sensory responses to otherwise non-irritating stimuli, presents unique challenges in both diagnosis and management. Due to the subjective nature of symptoms and the absence of universal clinical signs, SS diagnosis relies on a combination of subjective assessments, such as the SS-10, and objective measures like the LAST and TEWL to confirm sensitivity and skin barrier integrity. Individualized treatment approaches are essential, focusing on mitigating skin barrier dysfunction, reducing neurosensory hypersensitivity, and avoiding known irritants. Recent studies emphasize the importance of tailored strategies to manage SS, especially in patients who experience worsening symptoms from common allergens, preservatives, and environmental stressors.

The pathophysiology of SS underscores the importance of treating both the sensory discomfort and skin barrier impairment unique to each patient. By integrating recent advancements in SS assessment and management, clinicians can improve outcomes through personalized care plans that incorporate avoidance therapy, barrier repair, and pharmacologic options. As research continues to elucidate the underlying mechanisms of SS, a multidisciplinary approach to both prevention and management will remain key in addressing this condition’s complexity and improving patient quality of life.