Sensitive skin: an overview
Correspondence: Enzo Berardesca, San Gallicano Dermatological Institute, Via Chianesi 53, 00144 Rome, Italy. Tel.: +390652666157; fax: +390652666158; e-mail: email@example.com
Sensitive skin is a condition of subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sun screens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response.Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. A correlation between sensitive skin and constitutional anomalies and/or other triggering factors such as occupational skin diseases or chronic exposure to irritants has been hypothesized. Recent findings suggest that higher sensitivity can be due to different mechanisms. Hyper-reactors may have a thinner stratum corneum with a reduced corneocyte area causing a higher transcutaneous penetration of water-soluble chemicals. Alterations in vanilloid receptors and changes in neuronal transmission have been described. Monitoring skin parameters such as barrier function, proclivity to irritation, corneocyte size and sensorial transmission can also be useful to identify regional differences in skin sensitivity.
La peau sensible est une condition de l'hyperréactivité cutanée subjective à des facteurs environnementaux. Les sujets souffrant de cette condition signalent des réactions exagérées lorsque leur peau est en contact avec des cosmétiques, des savons et des écrans solaires, et ils mentionnent souvent une aggravation après une exposition à un climat sec et froid. Bien qu'aucun signe d'irritation ne soit généralement détecté, les démangeaisons, sensations de brûlure, de picotement et tiraillement sont constamment présentes. En général, les substances qui ne sont pas habituellement considérées comme irritantes sont impliquées dans cette réponse anormale. La peau sensible et l'irritation subjective sont largement répandues mais encore loin d'être complètement définies et comprises. Une corrélation entre la peau sensible et les anomalies constitutionnelles et / ou d'autres facteurs déclenchants tels que les maladies professionnelles de la peau ou l'exposition chronique à des irritants a été émise comme hypothèse. Des découvertes récentes suggèrent qu'une sensibilité augmentée peut être due à différents mécanismes. Les hyperréactifs peuvent présenter une couche cornée mince avec une zone de cornéocytes réduite entraînant une meilleure pénétration transcutanée de produits chimiques solubles dans l'eau. Des modifications des récepteurs vanilloïdes et des changements dans la transmission neuronale ont été décrits. La surveillance des paramètres de la peau telles que la fonction de barrière, la propension à l'irritation, la taille des cornéocytes et de la transmission sensorielle peut également être utile pour identifier les différences régionales dans la sensibilité cutanée.
Sensitive skin is a condition of subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sunscreens, and they often report worsening after exposure to dry and cold climate.
Although no sign of objective irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present [1, 2]. Objective signs are typically absent, but occasionally erythema , dryness or rash are described, as well as more intense inflammatory responses such as wheal . The signs and symptoms associated with sensitive skin have been reported to occur in conjunction with the menstrual cycle as well as in association with possible triggers like weather conditions, air conditioning, cleaning products, personal care products, and clothing .
Although initially believed to be an unusual reaction to common products, evidenced in only a small subset of consumers, epidemiological surveys surprisingly find a high prevalence of self-perceived sensitive skin across the industrialized world. In fact, most women in the United States, Europe and Japan believe that they have sensitive skin  (Table 1). In addition, the reported prevalences of self-perceived skin sensitivity have increased steadily over time, particularly among men .
Table 1. Prevalence of sensitive skin around the world
N = 408
N = 191
M and F,
N = 72
M and F,
N = 94
M and F,
N = 78
M and F,
N = 122
M and F,
N = 71
|U.S.A. (MS)||2010|| |
N = 57
M and F,
N = 4506
|74.7||Misery (2009) |
M and F,
N = 500
|70||Misery (2009) |
M and F,
N = 500
|59||Misery (2009) |
M and F,
N = 500
|60||Misery 2009 |
M and F,
N = 500
|59||Misery (2009) |
M and F,
N = 500
M and F,
N = 500
|90.6||Misery (2009) |
M and F,
N = 500
|86||Misery (2009) |
M and F,
N = 1006
|82||Misery (2009) |
|U.S.A. (OH)||2006|| |
N = 1039
|68.4||Farage (2009) |
N = NA
|~50||Johnson (1992) |
N = 25
|64||Farage (2008) |
N = 400
18–80 years N = 2101
|59.9 F||Sparavigna (2005) |
N = 1006
Epidemiological studies have been carried out to assess whether there is a correlation with sex, age, skin type or race .
Sensitive skin has historically been self-reported far more often in women than in men. It is believed that there exist a biological plausibility for greater sensitivity, as thickness of the epidermis was observed to be greater in men than in women (P < 0.0001) , and hormonal differences which may produce inflammatory sensitivity in women have also been demonstrated [9, 10]. Objective irritant testing, however, for the most part finds no differences . In addition, self-reports of sensitive skin among men have steadily increased over the last decade (in concert with increased advertising of sensitive skin products marketed to men), and a recent study in 1039 subjects found a 68.4% prevalence of self-reported sensitive skin, with no difference between men and women .
Hyper-reactors may have a thinner stratum corneum with a reduced corneocyte area causing a higher transcutaneous penetration of water-soluble chemicals . Frosch and Kligman , by testing different irritants, showed a 14% incidence of sensitive skin in the normal population, likely correlated with a thin permeable stratum corneum which makes these subjects more susceptible to chemical irritation.
Moreover, the declined barrier function in sensitive skin has already been reported as the result of an imbalance of intercellular lipid of stratum corneum . Although impaired barrier function is easily understood as a mechanism of sensitive skin, other factors are also possible implications such as changes in the nerve system and/or the structure of the epidermis. In a study , detailed characteristics of sensitive skin have been investigated using non-invasive methods. Sensitive skin has been classified into three different types based on their physiological parameters. Type I has been defined as the low barrier function group. Type II has been defined as the inflammation group with normal barrier function and inflammatory changes. Type III has been specified as the pseudo-healthy group in terms of normal barrier function and no inflammatory changes. In all types, a high content of nerve growth factor has been observed in the stratum corneum, relative to that of non-sensitive skin. Both in types II and III, the sensitivity to electrical stimuli was high , as these data suggest that the hypersensitive reaction of sensitive skin is closely related to nerve fibres innervating the epidermis. Yamasaki and Gallo  proposed recently that the innate immune system triggers an abnormal inflammatory reaction that mediates the symptoms of rosacea and sensitive skin. If so, flushing, blushing erythema may be due to chronic inflammation. In particular, cathelicidin may play a role in inducing the cytokine cascade. Indeed, some forms of cathelicidin peptides were known to have a unique capacity to be both vasoactive and proinflammatory .
Direct connections were observed between unmyelinated nerve fibres and mast cells; stress in animal models induces substance P (SP) in unmyelinated nerve fibres which triggers mast cell degranulation with subsequent histamine release . Stress is commonly reported as a trigger for sensitive skin, and mast cell degranulation is supported by the finding that sensitive skin sufferers had higher density of mast cells and size of lymphatic microvasculature . Neurogenic inflammation probably results from the release of neurotransmitters such as substance P, calcitonin gene–related peptide and vasoactive intestinal peptide, which induce vasodilatation and mast cell degranulation. Non-specific inflammation may also be associated with the release of interleukins (IL-1, IL-8, prostaglandin E2, prostaglandin F2 and tumour necrosis factor-α).
Recent research efforts, however, are homing in on the molecular basis for sensory hyper-reactivity. Transient receptor potential, vanilloid family 1 (TRPV1) is a non-receptive, thermosensitive ion channel which reacts to noxious stimuli, most notably noxious heat and low pH. TRPV1 is expressed on fibroblasts, mast cells and endothelial cells; activation results in pain or pruritus with a burning component. TRPV1 is also dramatically upregulated by inflammatory mediators .
Materials and methods
Some authors documented a higher reactivity to objective irritants mostly in women; some others noted that male subjects were directionally or significantly more reactive than females . Other experimental studies did not confirm this observation. Bjornberg , using six irritants by patch test application, found no sex-related differences. Moreover, Lammintausta et al. , studying the response to open and patch test application of SLS, found mild interindividual variations in transepidermal water loss (TEWL) and dielectric water content (DWC) values but no sex-related differences in the reaction pattern.
In 1982 Frosch and Wissing , using dimethylsulphoxide, demonstrated a correlation between the minimal erythema dose (MED) and the response to irritants: the higher the inflammation, the lower the MED. Subsequently, a correlation between skin reactivity and skin type was reported: higher reactions were detected in subjects with skin type I . However, in a total of 110 subjects covering all six skin types, the SLS dose response generated applying the substance under 4-h occlusion demonstrated that there was no significant difference between the groups. Even for type VI skin, the dose–response curve fell within the general pattern . In fact conflicting findings have been reported on the incidence of allergic contact dermatitis in different races [25-28]. Whereas there is a clinical consensus that blacks are less reactive and Asians are more reactive than Caucasians, the data supporting this hypothesis rarely reach statistical significance .
Conflicting data have also been found on subjective (sensory) irritation. Frosch reported that most common ‘stingers’ were light-complexioned persons of Celtic ancestry who sunburned easily and tanned poorly . Grove found no skin-type propensity to stinging; he noted that increased stinging was related mainly to the person's history of sensitivity to soaps, cosmetics and drugs . Arakami, instead, found no significant differences after SLS testing, but significant subjective sensory differences between Japanese and German women. So he concluded that Japanese women may complain about stronger sensations reflecting a different cultural behaviour rather than measurable differences in skin physiology; however, a faster penetration of SLS in Japanese cannot be excluded .
Moreover, skin reactivity is enhanced in eczema . Studies carried out on animal models demonstrated that strong irritant reactions in guinea pigs significantly reduced the threshold of skin irritation . On the other hand, hyporeactive states may be induced by skin treatment. Subclinical dermatitis, after repeated cutaneous irritation by open application, may induce skin hyporeactivity . This can also be one of the mechanisms of false-negative patch test.
Skin reactivity seems also to change depending on age, although contradictory findings are reported. For example, Nilzen and Voss Lagerlung  observed higher reactivity patch test reactions to soaps and detergents in elderly, whereas Bettley and Donoghue  reported a lower reactivity in the same group. Coenraads  demonstrated a higher skin reactivity to croton oil in the older patient group, but no differences by testing thimochinone or croton aldehyde. In 1993 Grove , by testing croton oil, cationic and anionic surfactants, weak acids and solvents, reported a lower susceptibility in older subjects in terms of less severe skin reactions. Robinson  confirmed this lower reactivity, in fact in his study the oldest age cluster of subjects (56–74 years of age) was directionally or significantly less reactive than the younger age clusters. Moreover, Wohrl noted that although the rate of positive reactions to nickel and thimerosal decreased with age, fragrance mix and metallic mercury stayed at the same level throughout all ages . The overall sensitization rate was highest in children <10 years old and decreased steadily, to be lowest among patients more than 70 years.
Patients over 70 years of age seem to have a reduced inflammatory response either to chemical irritants or to irritation induced by UV light . The UVB-induced, increased in both TEWL and DNA synthesis were significantly diminished, with decreased epidermal hyperplasia evident, in intrinsically aged versus young mouse epidermis .
On the other hand, following skin irritation, increased TEWL values were recorded in the older subjects compared to the young. This finding could be related to a deficient barrier recovery in the elderly. Moreover, the skin of women in menopause becomes more sensitive to various environmental threats. It has been reported that the skin gets more sensitive in women at the beginning of the menopause. This can be due to the fact that at this stage the skin becomes thinner, with a decrease in its function as a barrier that leads to a higher percutaneous absorption .
Studies identified self-declared sensitive skin using a standard sensitive skin questionnaire. The skin irritation of feminine hygiene products were compared using the cumulative skin irritation patch test. No significant difference was seen between the self-declared sensitive and normal populations (71–72).
Sensitive skin can be defined in both subjective and objective terms. Subjective perceptions of sensitive skin are derived from patient observations regarding stinging, burning, pruritus and tightness following various environmental stimuli. Because of the lack of clinical signs, the phenomenon of sensitive skin is difficult to document. Attempts to identify clinical parameters in subjects with subjective irritation indicate that these individuals tend to have a less hydrated, less supple, more erythematous and more teleangiectatic skin, compared to the normal population. In particular, significant differences were found for erythema and hydration/dryness .
The face has demonstrated to be the most common site of skin sensitivity, predictable physiologically owing to the larger and multiple number of products used on the face (particularly in women), a thinner barrier in facial skin, and a greater density of nerve endings  The nasolabial fold was reported to be the most sensitive region of the facial area, followed by the malar eminence, chin, forehead and upper lip [44, 45]. Saint-Martory et al.  found hand, scalp, feet, neck, torso, and back sensitivity followed facial sensitivity in descending order of prevalence. Significant numbers of individuals experience sensitivity of the scalp [46, 47]. One-third of the population interviewed reported sensitive scalp with higher levels in women than in men. Interestingly, the prevalence declared sensitive scalp increasing with age. The authors explain this could be due to alterations of nerve endings because of the ageing process or increased proclivity to irritation as a consequence of chronic exposure to surfactants contained in shampoos. The genital area is another site frequently affected by sensitive skin.
In a study of 1039 men and women, 56.2% reported sensitivity of genital skin , an area of particular interest as it is formed partially from embryonic endoderm and therefore differs from skin at other body sites . A surprising 56.2% of responders claimed sensitive genital skin, with significantly more African Americans than Caucasians (66.4%, P < 0.0001), claiming sensitivity of this area. Rough fabrics were found to be the most common offender for sensitive skin in the genital area .
Objective quantification of sensitive skin
It is difficult to find accurate parameters for categorizing skin as sensitive or non-sensitive; this condition often lacks visible, physical or histologically measurable signs. Subjects with sensory irritation tend to have a less hydrated, less supple, more erythematous and more teleangiectatic skin, compared to the normal population. In particular, significant differences were found for erythema and hydration/dryness . Tests for sensitive skin are generally based on the report of sensation induced by topically applied chemicals. Consequently, the use of self-assessment questionnaires is a valuable method to identify ‘hyper-reactors’  and a useful tool for irritancy assessment of cosmetics .
Sensory testing methods
Psycophysical tests based on the report of sensation induced by topically applied chemical probes have been increasingly utilized to provide definite information on sensitive skin. These methods of sensory testing can be validated by the use of functional magnetic resonance imaging (fMRI) which represent one of the most developed forms of neuroimaging. This technique measures changes in blood flow and blood oxygenation in the brain, closely related to neural activity manifested as sensory reaction . Querleaux et al. evaluated two groups according to their self-perceived characterization using a dedicated questionnaire about their skin reactivity. Event-related fMRI was used to measure cerebral activation associated with skin discomfort induced by a simultaneous split-face application of lactic acid and of its vehicle.
In both groups, skin discomfort owing to lactic acid increased activity in the primary sensorimotor cortex contralateral to application site and in a bilateral fronto-parietal network including parietal cortex, prefrontal areas around the superior frontal sulcus and the supplementary motor area. However, the activity was significantly higher in the sensitive skin group. Most remarkably, in the sensitive skin group only, activity spread into the ipsilateral primary sensorimotor cortex and the bilateral peri-insular secondary somatosensory area .
Quantification of cutaneous thermal sensation
In dermatology thermal sensation testing analysis is the most utilized quantitative sensory testing (QST) technique . It assesses function in free nerve endings and their associated small myelinated and non-myelinated fibres. This method is able to measure quantitatively the threshold for warm and cold sensation as well as hot and cold pain. Yosipovitch and coworkers used this technique to evaluate ethnic differences in sensorial irritation and perception of pain (with and without stratum corneum stripping), finding no major differences among Asian skin .
Stinging test has been used as a method for the assessment of skin neurosensivity. Stinging seems to be a variant of pain that develops rapidly and fades quickly any time the appropriate sensory nerve is stimulated. The test relies on the intensity of stinging sensation induced by chemicals applied on the nasolabial fold . Procedure differs depending on the chemical utilized. It is still not sure how it relates to identifying sensitive skin as high variation in the results is observed with these tests.
After a 5- to 10-min facial sauna, an aqueous lactic acid solution (5% or 10% according to different methods) is rubbed with a cotton swab on the test site whereas an inert control substance, such as saline solution, is applied to the contralateral test site. After application, within a few minutes, a moderate to severe stinging sensation occurs for the ‘stingers group’. Subjects are then asked to describe the intensity of the sensation using a point scale. Hyper-reactors, particularly those with a positive dermatologic history, have higher scores. Using this screening procedure, 20% of the subjects exposed to 5% lactic acid in a hot, humid environment were found to develop a stinging response . Lammintausta et al.  confirmed these observations identifying in his study 18% of subjects as stingers. In addition, stingers were found to develop stronger reactions to materials causing non-immunologic contact urticaria, to have increased transepidermal water loss and blood flow velocimetry values after application of an irritant under patch test.
An alternative test involves the application of capsaicin. Recently a new procedure assessed by Jourdain et al.  appears to be accurate and reliable for the diagnosis of sensitive skin. After a facial cleansing five increasing capsaicin concentrations in 10% ethanol aqueous solution are applied on the nasolabial folds. The formulation of capsaicin in hydroalcoholic solution accelerates the action of capsaicin on the face in comparison with the previously used 0.075% capsaicin emulsion, without being associated with painful sensation.
The capsaicin detection thresholds are more strongly linked to self-declared sensitive skin than the lactic acid stinging test .
The alternative application of 90% aqueous DMSO has not the same efficacy of lactic acid or capsaicin stinging test, and after application, intense burning, tender wheal and persistent erythema often occur in stingers.
Nicotinate and sodium lauryl sulphate (SLS) occlusion test
A different approach to identify sensitive skin relies on vasodilation of the skin as opposed to cutaneous stinging. Methyl nicotinate, a strong vasodilator, is applied to the upper third of the ventral forearm in concentrations ranging from 1.4 to 13.7% for a 15-s period. The vasodilatory effect is assessed by observing the erythema and the use of laser doppler velocimetry (LDV). Increased vascular reaction to methyl nicotinate was reported in subjects with sensitive skin . Similar analysis can be performed following the application of various concentrations of SLS.
Evaluation of itching response
Itchy sensation seems to be mediated by a class of C fibres with an exceptionally lower conduction velocity and insensivity to mechanical stimuli .
Indeed, no explanation of the individual susceptibility to the itching sensation without any sign of coexisting dermatitis has been found. Laboratory investigations have also been limited.
An itch response can be experimentally induced by topical or intradermal injections of various substances such as proteolytic enzymes, mast cell degranulators and vasoactive agents.
Histamine injection is one of the more common procedures: histamine dihydrochloride (100 μg in 1 mL of normal saline) is injected intradermally in one forearm. Then, after different time intervals, the subject is asked to indicate the intensity of the sensation using a predetermined scale, and the duration of itch is recorded. Information is always gained by the subject's self-assessment.
A correlation between whealing and itching response produced by applying a topical 4% histamine base in a group of healthy young females has been investigated .
The cumulative lactic acid sting scores were compared with the histamine itch scores in 32 young subjects: all the subjects who were stingers were also moderate to intense itchers, whereas 50% of the moderate itchers showed little or no stinging response .
Furthermore the histamine-induced itch sensation decreases after topically applied aspirin . This result can be attributed to the role that prostaglandins play in pain and itch sensation .
Washing and exaggerated immersion tests
The aim of these tests is to identify a subpopulation with an increased tendency to produce a skin response.
In the washing test , subjects are asked to wash their face with a specific soap or detergent. After washing, individual sensation for tightness, burning, itching and stinging is evaluated using a point scale previously determined.
The exaggerated immersion test is based on soaking the hands and forearms of the subjects in a solution of anionic surfactants (Sodium Lauryl Sulphate) at 40°C, for 20 min. After soaking, hands and forearms are rinsed under tap water and patted dry with a paper towel. This procedure is repeated two more times, with a 2-h period between each soaking, for two consecutive days. Prior to the procedure, baseline skin parameters are evaluated. The other evaluations are taken 2 h after the third and sixth soakings and 18 h after the last soaking (recovery assessment). All of the skin parameters are performed after the subjects have rested at least 30 min at 21 ± 1°C.
Behind-the-knee test (BTK)
A second method of exaggerating conditions in the testing of consumer products is the behind-the-knee (BTK) protocol which employs the popliteal fossa as a test site. BTK testing consists of the test product placed behind the knee and held securely by an elastic knee band, which in the course of daily activities adds a crucial mechanical friction component to the traditional testing .
Levels of irritation produced in BTK testing are consistently higher than those achieved with standard patch testing because of the frictional irritation screening in addition to just chemical. BTK testing, in conjunction with the other two approaches below, has proven useful in the development of potentially valuable protocols for sensitive-skin testing, specially when self-declared vs. normal populations are tested side by side with same products. Visual grading of erythema, the method of choice for many years, achieves a high degree of reproducibility with trained graders. A novel approach, however, utilized cross-polarized light which allows visualization of the skin at a depth of 1 mm below the surface. Following minor irritation produced by low-level sodium lauryl sulphate (SLS), subsurface visualization provided no improvement over visual scoring. In BTK, however, enhanced visual scoring through subsurface visualization detected significant differences in irritation produced by two different test products, differences that were visible on the first day . Enhanced visual scoring was used successfully with traditional patch testing, forearm controlled application test (FCAT) and BTK, providing a first link between sensory and physiological effects. Subclinical changes were apparent after initial exposure; enhanced visualization was able to correlate subclinical effects with consumer's preferences between products , a correlation which had not been verifiable in prior testing.
Enhanced visualization was also evaluated in the genital area of symptomatic patients, demonstrating that cross-polarized light may be useful in diagnosing subclinical inflammation in ostensibly sensory vulvar conditions .
A study of facial tissues, with and without lotion, evaluated four versions of facial tissues by employing repeated wiping to accentuate irritation. Affected skin had been compromised by tape stripping prior to the initiation of wiping. Erythema, as well as dryness, was evaluated daily. Statistical analysis revealed that the panelists' subjective product preferences were more consistent in distinguishing between the test product than were the visuals signs (erythema and dryness) .
Owing to the multifactorial pathogenesis of the disorder, there is no standardized and/or validated treatment for sensitive skin. However, several actives can be used to control or improve the various aspects of sensitive skin. In particular, moisturizers (sensitive skin is usually a dry skin) and optimized lipid mixtures can be used to improve barrier function. Anti-inflammatory compounds (i.e. flavonoids and similar compounds) can minimize inflammatory reactions and modulate vascular reactivity as well as antioxidants. Specific inhibitors of vanilloid receptors have been also shown to be effective .
Sensitive skin represents a widespread condition of susceptibility to exogenous factors. To find an effective approach to improve sensitive skin, it is important to know the detailed mechanism of sensitive skin. The reason why some subjects react with subjective symptoms like itching, burning, stinging, prickling or tingling is unclear. An increased permeability of the stratum corneum and acceleration of the nerve response in skin are considered to be involved. Approximately 70% of the population consider themselves to possess the characteristics of sensitive skin, and 50% of these patients with sensitive skin demonstrate these uncomfortable symptoms without accompanying visible signs of inflammation. Non-invasive evaluation of sensitive skin may successfully predict individual susceptibility to cosmetic-related adverse reaction. All of the efforts in this direction appear undoubtedly important to improve tolerance to the majority of cosmetic products. Moreover, if sensitive skin involves several different causes, skin treatment must be selected to fit each mechanism. An appropriate approach to improve the sensitivity skin screening and syndrome should be taken considering the different mechanism of skin sensitivity among various skin types.
The paper has not been supported by any funding.