A number of physiological differences have been identified in individuals with SSS (Table 1). The epidermal layer of the skin of individuals with SSS has reduced barrier integrity due to differences in lipid composition with a decrease in ceramide and sphingolipid content [8]. This results in increasing the potential penetration of irritants and insufficient protection of nerve endings [5,8,9,10]. Increased vascular reactivity has been observed in individuals with SSS, resulting in more intense vascular reactions to irritants [11]. Roussaki–Schulze and colleagues reported that vascular reactions to methyl nicotinate in SSS subjects was 75 times higher compared to non-sensitive controls [12].

Neurosensory dysfunction is another physiological element that contributes to SSS. Biopsies from SSS subjects demonstrated a decrease of peptidergic C-fiber density [14]. These fibers are involved in pain, itching and temperature perception. Degeneration of these fibers can induce hyper-reactivity of the remaining nerve endings and a result in allodynia [11]. An additional neurosensory component is an increase in Transient Receptor Potential Vanilloid-1 (TRPV1). This is a non-selective cation channel that responds to heat and low pH, and is related to nociception, neurogenic inflammation, and pruritus. TRPV-1 is also classically known as the capsaicin receptor [15,16]. Based on self-reported SSS skin biopsies, Ehnis–Pérez et al. found TRPV1 is dramatically upregulated in sensitive skin subjects [15].

Another important factor for SSS people is that they may also suffer from skin co-morbidities and additional skin disorders (Table 2). Just like SSS, rosacea is more common in individuals who are female with fair skin and hair, blue eyes, and lighter skin, i.e., phototypes I–III [17]. In a genome-wide association study (GWAS) involving 22,952 subjects, Chang and colleagues determined that rosacea is associated with several HLA alleles [18]. This is in line with the inflammatory nature of the syndrome. In a study involving 1000 individuals in Korea, 56.8% of whom had sensitive or very sensitive skin, Kim and colleagues found that the SSS group was over 3 times more likely to suffer from acne, atopic dermatitis, and facial blushing, and over 2 times more likely to suffer from seborrheic dermatitis compared to the non-sensitive group [19]. Brenaut and colleagues found a similar result in an Indian population [20]. In a study involving over 3000 individuals, SSS subjects were 2–4 times more likely to report atopic dermatitis, acne, psoriasis, vitiligo, rosacea, or contact dermatitis compared to the non-sensitive group [20].

Sensitive skin has also been linked to sensitive eyes and eyelids, and irritable bowel syndrome [26,27]. It is proposed that these conditions may be related to the neurosensory dysfunctions identified in SSS, i.e., hyperexcitability of nerve endings, hyperactivation of sensor proteins resulting from upregulation of TRP channels, and alterations in nerve fiber density [26]. The histological findings and clinical signs of small fiber impairment with SSS are similar to those experienced in small-fiber neuropathy [28].

As part of a GWAS, Farage et al. evaluated 23,426 subjects’ responses and found that SSS individuals reported other skin complaints, specifically, contact dermatitis, freckles, atopic dermatitis, acne, and seborrheic dermatitis [25]. These authors found an association between SSS and several specific loci also associated with genes for rosacea, pigmentation, and skin cancer [25].

Aging can be another physiologic factor in sensitive skin. As an individual ages, the skin changes as it becomes thinner and drier, as well as replacing itself at a slower rate [29]. The elderly skin is also more prone to higher permeability but a reduced elasticity, tensile strength, vascularization and cellularity [29]. These physiological changes might lead one to conclude that older skin is more susceptible to irritant effects, and more likely to be sensitive. However, clinical assessments using known irritant materials suggest that skin irritation susceptibility generally decreases with age, as does the capacity to produce visible physiological signs of dermatological irritation [9,29,30,31,32]. Several studies have shown that the prevalence of SSS in older individuals is no different or lower than in younger individuals [19,23,33,34]. A 2010 study with 1039 individuals evaluated SSS at several body sites in the US [29]. No consistent pattern with age was seen when subjects were asked about sensitive skin in general, of the face or body, specifically. However, genital area skin sensitivity demonstrated an increase from 53% in subjects ≤ 30 years old to 66% in subjects ≥ 50 years old. This difference was mainly due to the females in the study.

Another critical factor is the impact of hormonal fluctuations during the different consumer life stages on skin sensitivity. In both the dermis and epidermis, the skin has highly sensitive estrogen receptors, and variation of female hormones can have an impact on the skin [38]. Decreased estrogen levels can adversely affect barrier function, elasticity, blood circulation and vasomotor function. Farage’s study which included 1039 individuals demonstrated that the menstrual cycle was contributing to unpleasant genital skin in 61% of women with SSS and 40% of the non-sensitive skin women (p < 0.00001) [37]. Falcone and colleagues reported that women with more intense perimenstrual symptoms perceived their skin as more sensitive during some phases of the menstrual cycle compared to women with lower intensity symptoms (p = 0.002) [39]. Furthermore, 70% of postmenopausal women claiming SSS perceived their skin sensitivity increasing after menopause [39]. In general, among SSS women, products used for menstrual protection and hygiene have been shown to trigger significantly greater symptoms than non-sensitive women [37].