[ZKKL] Academic Sharing | Advances in Research on the Etiology of Sensitive Skin

1.1 HLA-II Gene-Related

Major histocompatibility complex The major histocompatibility complex (MHC) genes are involved in The regulation of hypersensitivity reactions was demonstrated as early as the late 20th century. Immunology holds that various antigens are primarily governed by MHC class II genes upon entry into the organism, in… After the peptide-binding groove of human leukocyte antigen (HLA) molecules binds to an antigen-presenting cell (APC), the resulting complex is presented on the APC surface and recognized by HLA class II–restricted T cells, leading to an imbalance between Th1 and Th2 responses. Th2 cells secrete interleukin‑4 (IL‑4) and interleukin‑13 (IL‑13), which in turn promote the production of immunoglobulin E (IgE). Studies have shown that among Han Chinese individuals, patients positive for house dust mite antigens exhibit increased frequencies of the HLA‑DR3 and HLA‑DR7 alleles [4], thereby contributing to the pathogenesis of atopic dermatitis (AD). In contrast, other HLA‑DR loci do not display a specific association with AD. Additionally, research has demonstrated that elevated frequencies of HLA‑DR7 and DR4 are linked to sensitization reactions [5], while in the British population, an increased frequency of the HLA‑DQA1*0301 allele is associated with the development of allergic reactions [6]. Furthermore, a Japanese study found that elevated frequencies of HLA‑DRB1*1302, DQB1*0406, and DPB1*0301, along with reduced frequencies of HLA‑DR4, DR53, and DQB1*0406, are all correlated with specific immune responses [7].

Although the aforementioned studies differ in their populations, methodologies, and findings, it is clear that skin sensitivity in human populations may be influenced by multiple genetic loci and their respective allele frequencies, with specific immune responses being associated with the HLA‑DR gene. The interplay between the diversity of HLA loci and the peptide‑binding grooves of exogenous antigens, as well as their implications for cutaneous manifestations and the magnitude of immune responses, remains unclear.

1.2 Gene Region–Related

Online Mendelian Inheritance in Man (OMIM) lists “11q13.5, 13q‑12‑q14, 5q131‑q33, 3q21, 1q21, 17q25, and 20p gene linkage” as susceptibility loci for Alzheimer’s disease (AD). Susceptibility loci vary across populations: in Germany, the AD‑associated locus is 11q13.5 [8]; in Japan, susceptibility has been mapped to 1q24 and 15q21 [9]; and recent studies have identified 5q22.1 and 20q13.33 as risk loci in the Han Chinese population [10]. As research progresses, the number of candidate and newly discovered genetic regions continues to grow; for example, a 2011 study based on European cohorts reported additional susceptibility loci at 11q13, 19q13.2, and 5q31.1 [11], while Japanese studies have identified new risk loci at 2q12, 3q13.2, 3q21.33, 7q22, 10q21.2, 20q13, 6p21.3, and 11p15.4 [12]. In the Han Chinese population, 1q21.3 and 11q13.1 have been implicated as AD risk genes [13]. With the accumulation of evidence, OMIM is likely to incorporate more precisely defined susceptibility loci, underscoring the importance of further investigating the genetic architecture of AD in the Han Chinese population.

Allergic reactions exhibit distinct characteristics across different age groups. Infants and young children have a higher incidence of food‑related allergies. Clinical studies have demonstrated that among the Han Chinese population, 84.6% of patients with atopic dermatitis (AD) develop the condition within the first two years of life, and male infants tend to experience more severe disease than females [14]. Multiple statistical analyses of eczema and AD have corroborated this observation [15].

Adolescents are prone to inhalant and contact allergies, while young and middle-aged women are more likely to develop facial skin problems. For instance, studies have shown that among individuals with hormone‑dependent dermatitis, 86.5% are female, and 56.8% are young to middle‑aged women aged 20–40 [16]. In contrast, older adults tend to exhibit weaker responses to previously encountered allergens and a lower likelihood of developing new allergic reactions; however, dryness‑related pruritus resulting from decreased skin hydration may give rise to additional skin concerns.

2.1 Infants and Young Children with Food Allergies

More than 60% of children with eczema have a link to food allergies [17]. In infants and young children, cow’s milk and egg allergies [18] predominantly occur within the first year of life and are associated with dysbiosis of the gut microbiota [19]. Allergic reactions in this age group correlate with reduced colonization by bifidobacteria and lactobacilli, increased levels of enterobacteria and staphylococci, a lower proportion of anaerobic bacteria, and a higher proportion of aerobic bacteria [20]. Due to microbial imbalance, a stable biological barrier fails to develop, and the immature immune system exhibits diminished immune responses, resulting in heightened intestinal permeability. This allows harmful substances—such as transitory bacteria, food antigens, and pro-inflammatory cytokines—to enter the systemic circulation, triggering food allergies and a cascade of cutaneous inflammatory reactions [21]. The persistently elevated rate of skin inflammation observed into adulthood may stem from ongoing microbial stimulation that influences the development and maturation of intestinal lymphoid tissues during childhood [22]. Current research points to alterations in the gut microbiota as a key factor in allergic diseases; consequently, prospective studies investigating the qualitative and quantitative relationships between dietary factors and the gut microbiota—including species composition, abundance, and functional characteristics—pose significant challenges, and the long-term implications for these children once they reach adulthood remain to be fully elucidated.

2.2 Adolescents and Inhalant Allergies

As children grow and their lifestyles and environments change, they gradually develop immune tolerance to food allergens encountered during early childhood. In contrast, sensitization to inhalant allergens tends to increase during adolescence. Both domestic and international studies on inhalant allergens have yielded relatively consistent findings, with house dust, mold mites, cockroaches, and pollen being the most commonly implicated agents [23]. Inhalant allergies may be associated with high‑affinity IgE receptors on the epidermis; these receptors specifically bind relevant antigens, triggering an allergic response in the respiratory mucosa that can further precipitate cutaneous inflammation. Additionally, a study conducted in the Korean population demonstrated that elevated total IgE levels in children with cockroach‑induced inhalant allergy were correlated with higher serum vitamin D concentrations [24]. The consistency of findings regarding inhalant allergens across different regions suggests similarities in atmospheric composition and inhaled substances; however, this does not rule out the possibility that undetected inhalant components could also elicit allergic reactions. Moreover, the quantitative relationships between inhaled allergens and the occurrence of allergic responses, as well as their associations with serum biomarkers, remain unclear.

2.3 Young and Middle-Aged Women with Recurrent Facial Dermatitis

Clinical statistics indicate that this condition primarily affects young and middle-aged women, likely due to their heightened concern for skin health during this life stage. Inappropriate skincare or treatment—particularly the use of cosmetics or medications containing allergenic substances or hormones—can trigger hypersensitivity reactions. Moreover, hormonal agents may interfere with cellular DNA synthesis and mitosis, thereby suppressing the proliferation of epidermal keratinocytes and other cells. Cell proliferation and differentiation [25]. Ultimately, this leads to increased transepidermal water loss (TEWL), thinning of the stratum corneum, abnormal skin architecture, and dysregulation of skin functions, resulting in heightened responsiveness to irritant stimuli and exaggerated immune reactions. The most commonly affected areas are the infraorbital region, the malar area, and the forehead, with clinical manifestations primarily including dryness, scaling, erythema, pruritus, and burning pain.

2.4 Elderly Women and Pruritus

As age advances and the skin accumulates greater experience, cutaneous sensory nerve function declines, neural innervation diminishes, and tolerance increases, so new sensitizing agents may no longer constitute the primary source of discomfort in older adults. However, with aging, sebaceous glands atrophy, transepidermal water loss (TEWL) decreases, and the skin’s capacity to synthesize hyaluronic acid wanes [26], leading to dryness and desquamation‑related pruritus driven by reduced sebum production—conditions that emerge as distinct clinical challenges. Senile pruritus has been linked to IgE‑mediated hypersensitivity; meanwhile, Chen Zairong et al. [27] propose that IgG4 is a specific antibody implicated in elderly‑onset cutaneous pruritus, primarily mediating allergic responses to food and inhalant antigens. These findings underscore that hypersensitivity can be mediated by multiple specific antibodies, offering new avenues for research in allergen detection.

3.1 Allergens

Allergens can be classified according to their route of entry into contact, inhalation, and… Inhalation, ingestion, and injection. Due to differences in diagnostic methods and study populations, the findings are complex and variable. According to incomplete statistics and clinical observations, inhalant allergens are predominantly dust mite antigens, food allergens are mainly cow’s milk and shrimp, contact allergens are primarily pollen, and facial contact allergens are chiefly cosmetics; skin allergies outside the face are more commonly associated with topical ointments. Among drug‑induced allergic reactions, β‑lactam antibiotics are the most frequent culprits, and penicillin allergy has been linked to the HLA‑DR9 gene [28]. Research into the relationship between allergen‑triggered hypersensitivity reactions and the diversity of cutaneous manifestations, as well as their association with HLA genes, may emerge as a new research frontier. Current diagnostic approaches include skin prick testing, intradermal testing, patch testing, serum allergen detection, gene‑chip technology, and bioresonance allergen testing. Notably, bioresonance allergen testing has come under scrutiny due to the lack of evidence‑based support [29].

3.2 Humid Environment

Sensitive skin is affected by sunlight, temperature, season, and the environment. The interplay of multiple factors, including pollution, contributes to this condition; many studies attribute microbial invasion as the primary cause of skin sensitivity in individuals with dermatitis and eczema. Research has shown that the overall bacterial detection rate on the skin of patients with dermatitis and eczema is 67.78%, with Staphylococcus aureus and Malassezia detected at rates of 31.11% and 47.78%, respectively [30]. Microbial proliferation can compromise the skin barrier; Staphylococcus aureus can penetrate the AD‑affected skin barrier, inducing alterations in IgE levels [31], while Malassezia furfur mediates elevated IgE in AD patients, triggering type I hypersensitivity reactions [32].

In fact, the human body harbors a wide variety of microorganisms. In biological terms, only under conditions of high humidity and moderate temperature can the skin quickly become an ideal growth medium for certain microorganisms. When the skin’s microbial balance is disrupted, pathogenic microbes that thrive in such conditions proliferate and invade the epidermal layer, ultimately triggering skin allergies. Moreover, in humid environments, variations in temperature and moisture further exacerbate these issues. Research into the mechanisms by which skin diseases arise warrants close attention.

The causes of skin sensitivity are multifactorial, and clinical diagnosis and treatment also… It is a key factor influencing prognosis. For physicians, solid clinical skills are of course essential, but guiding patients to identify underlying causes, encouraging the prudent use of cosmetics, and providing psychological support all play crucial roles. For patients, maintaining long-term self‑care, avoiding products with no clear origin or safety information, choosing appropriate skincare methods, and correcting habits such as smoking, picky eating, constipation, and irregular sleep patterns can all help improve skin concerns. At present, the etiology and pathogenesis of the cutaneous sensitivity system remain unclear, and in-depth research on the therapeutic and maintenance applications of medical‑grade cosmetics is still lacking. Consequently, how to select suitable medications and skincare regimens based on each patient’s skin condition has become a shared challenge for both clinicians and patients.