Exposome Impact on Nail Health

Abstract Background: The nail unit is a complex system with various components, each serving distinct functions. The exposome, encompassing external and internal factors such as UV radiation, air pollution, dietary habits, and cosmetic product usage, substantially influences nail health and can lead to premature nail aging. Summary: Internal and external exposomal factors can impact differently on nail health, inducing a variety of different clinical conditions. Effective therapeutic strategies exist, but a comprehensive understanding of how the exposome affects nails is lacking. This article aims to bridge this knowledge gap by exploring the relationship between the exposome and nail health, emphasizing it as a central focus of our analysis. Key Messages: (1) The exposome, comprising various external and internal factors, may significantly influence nail health negatively, leading to premature nail aging. (2) Different nail conditions may arise due to the exposomal influence on nails. (3) Understanding the exposome’s impact on nail health is crucial for developing solutions to mitigate negative effects and improve overall nail well-being.


Introduction
The nail unit is a complex system comprising various components, each with a distinct function.The exposome, which comprises a diverse range of external and internal factors such as UV radiation, air pollution, dietary habits, and the use of cosmetic products, significantly impacts overall nail health, promoting nail aging.Recognizing the relationship between the exposome and nail health is paramount to developing effective strategies aimed at mitigating the adverse effects of these factors; however, there remains a substantial gap in our understanding of how these factors impact nails.This paper seeks to address this gap by delving into the connection between the exposome and nail health, making it the central focus of our study.
Nail Structure: Physical and Chemical Properties Nails are primarily composed of keratin, a tough, fibrous protein that forms the core, providing strength and rigidity.More specifically, keratin is a protein rich in cystine, an amino acid provided with sulfur groups that enable the formation of stable disulfide cross-links [1,2].The hardness and flexibility of the nail plate result from the organization of keratin filaments within the corneocytes forming the nail plate [3].
Besides sulfur, calcium also plays a role in nail chemistry.It is primarily found in the form of phosphate within hydroxyapatite crystals in the cytoplasm or bound to phospholipids, particularly in the dorsal and ventral nail plates.Notably, the concentration of calcium in nails is approximately ten times higher than in hair, but its specific contribution to nail hardness remains a matter of debate [2,4].In addition, it is worth noting that healthy nails contain approximately 5% lipids, which are located in specific ampullar dilations within the dorsal plate and intercellular spaces in the ventral plate; these lipids are recognized as the primary contributors of nail hardness [5,6].They collaborate by cross-linking keratin fibers among the corneocytes, while hydrophobic interactions hold them together, ultimately forming a water-resistant layer [7].Although it is suggested that some nail constituents, such as calcium and lipids, may have extrinsic origins, their presence adds to the intricate chemical nature of nails [2,8].

Definition of Exposome and How It Affects Skin and Its Adnexa
The term "exposome" was coined in 2005 by an American cancer epidemiologist Christopher Wild to encompass all exposures an individual encounters from birth to death.It complements the human genome and aims to understand the impact of environmental exposures on health [9].The exposome includes both external and internal factors and how the body responds to them.The major categories of exposome factors related to skin aging include solar radiations (UV, visible light, and infrared), air pollution, tobacco smoke, nutrition, various miscellaneous factors, and cosmetic products [10].In general, these factors damage the layers of the skin, trigger the production of matrix-degrading enzymes, and lead to the synthesis of advanced glycation end products and other substances.They collectively contribute to the aging of the skin and its associated structures (e.g., hair and nails) [10], ultimately compromising their overall health.
For a more comprehensive understanding of how nail health is influenced, it is crucial to emphasize that both intrinsic factors (not included in Wild's exposome definition) and exposomal factors play a role in defining nail health.In the following discussion, we offer a thorough examination of both these categories.

Intrinsic Factors Impacting on Nail Health
Various intrinsic factors can affect nail health, including aging, genetics, hormones, and medical conditions.Among these intrinsic factors, the aging process of nails stands out as a significant influencer.

Aging
Aging substantially impacts nails, leading to various changes attributed to both the natural aging process and age-related diseases.Impaired peripheral circulation, often associated with arteriosclerosis, is one of the primary causes of these changes.Notable nail changes include alterations in color, contour, increased nail plate size, and shifts in chemical composition.The color of the nail plate often shifts from pale pink to yellow, gray, or white, appearing dull and opaque [11].Some individuals may exhibit "Neapolitan" nail plates, lacking lunula, featuring a white proximal section, a normal pink central band, and an opaque distal free edge.Additionally, multiple transverse white bands or longitudinal dark bands can appear [12,13].Alterations in the contour of senile nails often include increased transverse curvature and decreased longitudinal curvature.Conditions such as nail flattening (platyonychia), spooning (koilonychia) (Fig. 1a), and pincer nail deformity (Fig. 1b) are frequently observed [14].The chemical composition of the nail plate also undergoes changes as calcium levels increase while iron levels decrease, affecting the overall composition of the nail.Lastly, the proportions of lipid fractions change with age as well [12,14,15].
Aging may result in a slower growth rate of the nail plate, which may serve as an adaptive response for individuals with reduced eyesight and manual dexterity, making nail grooming challenging [12,16].Furthermore, changes in the growth process can lead to toenails thickening and curving sideways, resulting in conditions like onychogryphosis (Fig. 1c) and ingrown toenails (Fig. 1d).Trauma and ill-fitting shoes can cause subungual hematoma in elderly individuals, especially those on anticoagulant therapy.In contrast, fingernails become thinner with age and exhibit altered curvature in both longitudinal and transverse directions [12,17].

Genetics
Genetics also play a role in nail health, as demonstrated by various mutations that can lead to a range of clinical scenarios [18,19].Three principal molecular pathways significantly contribute to nail development.First, the WNT signaling pathway, comprising secreted glycoproteins called WNTs, plays a pivotal role in nail formation.Activation of WNT signaling is critical for the formation of the nail matrix, influencing cell proliferation and differentiation.Mutations in genes involved in the WNT signaling pathway can lead to nail disorders, such as ectodermal dysplasia associated with WNT10A gene mutations [18,20].The Notch signaling pathway, involving cell surface receptors called Notch receptors, helps maintain balance between stem cell self-renewal and differentiation in the nail matrix, crucial for nail growth.Dysregulation of Notch signaling can lead to nail disorders, affecting nail growth and integrity [18,21].Another crucial pathway is the bone morphogenetic protein (BMP) signaling pathway, involved in nail differentiation and maintaining the homeostasis of the nail bed.Mutations or dysregulation of BMP signaling components, such as MSX2 and FOXN1, can lead to nail disorders, affecting the formation, growth, and integrity of the nails; for instance, mutations in FOXN1 lead to nail dystrophy, congenital alopecia, and T-cell immunodeficiency [18,22].

Hormones
Hormones can also impact nail health, although the literature on this topic is limited.Erpolat et al. examined 312 pregnant women and found that 24.4% had leukonychia, the most common nail problem observed.Leukonychia can be caused by elevated estrogen levels during pregnancy, leading to matrix dysfunction and delayed keratin maturation.The second most common alterations were ingrown toenails and onychoschizia, both at 9.0%.Onychoschizia involves the splitting of the distal nail plate into layers at the free edge, possibly due to the rapid extension and softening of the nails during preg-nancy [23].Furthermore, there is evidence in the literature that increased estrogen and progesterone levels during pregnancy might thicken the nail plate [24].As for thyroid hormones, Rosenberg et al. [25] suggested that a deficiency of protein or amino acids may contribute to koilonychia, and that hyperthyroid patients who have high metabolic activity might develop hypoalbuminemia, leading to this condition.Finally, hypothyroidism may cause slow-growing and brittle nails due to decreased metabolic rate and vasoconstriction, which reduces blood flow; in contrast, hyperthyroidism might lead to fastgrowing nails due to vasodilation.

Exposomal Factors Impacting on Nail Health
The exposome can be defined as the cumulative impact of environmental factors and biological responses across an individual's lifetime, encompassing external exposures, dietary choices, lifestyle, and internal processes [26].The skin aging exposome, in particular, refers to the influences of exposomal factors on skin aging, and it comprises several major categories: nutrition, drugs, solar radiation (including ultraviolet, visible light, and infrared), air pollution and tobacco smoke, lesser explored miscellaneous factors, and cosmetic products [10].Nails  are a very important adnexal structure of the skin and can be affected by exposome factors as well.Exposomal factors can be divided into internal (Table 1) and external (Table 2), depending on the origin of the influence on nails.

Internal Exposomal Factors Nutrition
For what concerns the internal factors, nutrition is an internal exposomal factor that can influence nail health, as shown by how differently malnutrition can impact on the nail unit components [27].For instance, the nail bed can exhibit signs of nutritional imbalances; these include splinter hemorrhages (Fig. 2a, b), Terry nails, Muehrcke lines (Fig. 2c), and onycholysis.More specifically, splinter hemorrhages, often associated with subacute bacterial endocarditis, can also result from nutritional issues like scurvy (vitamin C deficiency) and hemochromatosis [27][28][29][30].Terry nails, which are brown-to-pink bands on the nail bed, are found in the context of malnutritive states and may be observed in the elderly [14,27,30].
Muehrcke lines, characterized by transverse white bands of pallor on the nail bed, are associated with hypoalbuminemia, malnutrition, and acrodermatitis enteropathica (due to zinc deficiency) [27,30,31].Lastly, among the potential causes of onycholysis, there are nutritional imbalances such as iron-deficiency anemia and pellagra (caused by the deficiency of vitamin B3) [27,28,30].
The nail plate, much like the nail bed, can undergo changes due to nutritional imbalances.These imbalances may lead to various nail conditions.As an example, transverse leukonychia can be associated with deficiencies in vitamin C, calcium, and zinc.Clubbing may result from imbalances related to factors like phosphorus, arsenic, alcohol, mercury, or beryllium exposure, as well as conditions like hypervitaminosis A or iodine deficiencyinduced cretinism (Fig. 2d).Koilonychia is commonly linked to iron-deficiency anemia.Hapalonychia, also known as soft nails, is often attributed to deficiencies in vitamins A, B6, C, D, and low serum calcium levels.Beau's lines are typically due to protein deficiency (Fig. 2e).Onychomadesis (Fig. 2f) and onychorrhexis can be related to deficiencies in iron and zinc, respectively, while trachyonychia may be associated with reduced dietary water and food intake, as well as zinc deficiency, which is particularly common among the elderly.These nutritional imbalances can result in a variety of nail conditions, underscoring the significance of maintaining a well-balanced diet for overall nail health [14,27,28,30,[32][33][34][35].
Drug-Induced Disorders Just like nutrition, the extensive landscape of exposomal pharmaceuticals has the potential to induce nail alterations.Clinical presentations depend on the specific nail component affected [36][37][38][39][40]. Drug-induced nail disorders can be categorized according to the specific nail component affected.Drugs can interfere with the kinetics and keratinization of keratinocytes in the nail matrix, giving rise to various nail conditions, including Beau's lines, onychomadesis, true leukonychia, nail fragility, and melanonychia.Beau's lines and onychomadesis are characteristic of acute nail matrix toxicity, which can also result from trauma or systemic illnesses, but drug-induced cases are suspected when they affect all nails uniformly [38][39][40][41].Specifically, onychomadesis and Beau's lines can be precipitated by various chemotherapeutic agents with a higher incidence following short-term, high-dose chemotherapy, particularly in the context of combination chemotherapy, such as docetaxel-cisplatin-fluorouracil therapy.Other common contributors to Beau's lines include radiation therapy and the use of retinoids [38][39][40]42].
True leukonychia is indicative of distal nail matrix toxicity and is often observed during treatment with specific chemotherapeutic agents (e.g., cyclophosphamide, vincristine, doxorubicin) but can also be caused by arsenic poisoning (Mees' lines) [39,40,43].Nail fragility, on the other hand, signifies mild nail matrix damage and is frequently noted in patients treated with retinoids, particularly problematic when used for nail psoriasis [38][39][40]44].Lastly, melanonychia results from the activation of nail matrix melanocytes by drugs, with the mechanism remaining unclear.Drug-induced melanonychia typically affects multiple nails, manifesting as light brown-to-black longitudinal or transverse bands.Various drugs, including azathioprine, psoralens, and cancer chemotherapeutic agents (e.g., doxorubicin, bleomycin, 5-fluorouracil, methotrexate), are considered potential culprits [38][39][40]45].Drugs can also affect the nail bed, giving rise to a distinct range of clinical manifestations.For example, onycholysis and photo-onycholysis result from acute nail bed toxicity, leading to detachment of the nail plate from the nail bed.Onycholysis is more prevalent and is typically associated with anticancer therapies (e.g., capecitabine or taxane-based regimens), while photoonycholysis is less common and usually secondary to psoralens plus UV irradiation [40,46,47].Apparent leukonychia, another sign of nail bed damage, can lead to white nail pigmentation due to alterations in the nail bed or circulation.It may present as "half-and-half nails" or Muehrcke lines, which can be side effects of chemotherapy drugs, differing from transverse true leukonychia as it fades with digital compression [40,48].
Periungual folds can also be impacted by drugs, resulting in conditions such as paronychia and pyogenic granulomas.Paronychia is characterized by inflamed, swollen, and painful nail folds and can be triggered by various drugs, including EGFR inhibitors, VEGF inhibitors, MEK inhibitors, taxanes, and antiretrovirals (Fig. 2g).This condition is also observed in patients with psoriasis undergoing retinoid treatment as it results from the retention of scales under the proximal nail fold [40,49].Pyogenic granulomas, common benign vascular tumors, can develop in response to drugs such as EGFR inhibitors and capecitabine (Fig. 2h) [40,50].Multiple pyogenic granulomas are described as typical adverse effects of treatment with retinoids and the antiretroviral protease-inhibitor indinavir [40,51].
Topical drugs can have various effects on nails.For example, a case of yellow nail discoloration, known as yellow chromonychia, was reported due to the use of a galenic topical preparation containing ascorbic acid and miconazole nitrate, intended for preventing nail fungal infections.The discolored nails typically exhibited a border near the cuticle, and discontinuation of the cream for 2 months resolved the issue [40,52].In addition, excessive use of a nail file in combination with amorolfine nail lacquer can lead to specific nail plate changes known as "amorolfine nails," characterized by thinning of the distal nail plate and reddening of the nail bed [40,53].Irritative and allergic reactions have also been reported, resulting from various topical drugs (e.g., imidazoles) and chemicals, leading to acute or chronic eczematous Prudkin/Cedirian/Santamaria/Jourdan/ Piraccini changes in the skin around the nails.Urea-containing topical products, commonly used for nail conditions, can cause irritant reactions when applied excessively or covered with tape [40,54].Finally, chemical leukoderma, a skin condition characterized by hypopigmentation due to repeated exposure to certain chemicals, is associated with aromatic and aliphatic derivatives of phenols and catechols, corticosteroids, mercurials, arsenics, p-phenylenediamine, azelaic acid, tretinoin, and systemic medications like chloroquine and fluphenazine.Prolonged use of topical steroids can also lead to temporary skin hypopigmentation [40,55].

Tobacco
Tobacco consumption also plays a key role in affecting nails' health.Although the exact impact of metabolic products from cigarette smoke on nails remains unclear, it is important to note that certain nail changes can still result from nicotine byproducts.Indeed, smoking can lead to yellow pigmentation of the nails, often referred to as the "nicotine sign" [56].This yellow discoloration is a common occurrence, especially among long-term smokers.The staining of nails by nicotine is described as a dynamic process; as new nail growth occurs, it gets stained by tobacco byproducts from side stream smoke.When someone suddenly quits smoking, a line of demarcation appears on the nails; this line can be used to estimate the timing of the cessation of smoking [57].Verghese et al. [57] reported two clinical cases where the line of demarcation on the nails was used to infer that the patients had stopped smoking due to recent illnesses.The appearance of the nails where a line of demarcation separates the yellow, nicotine-stained portion from the newly grown, pink nail is known as "harlequin nail."Furthermore, the effect of tobacco on nails is also used to measure smoke exposition as researchers found strong correlations between maternal and infant hair and nail nicotine levels; indeed, it seems that newborn hair and nail can be valuable predictors of fetal exposure to cigarette smoke [58].Additionally, infant nail nicotine levels The Effect of the Different Exposomal Factors on Nail Health appeared to be higher than infant hair nicotine levels, potentially reflecting the earlier development of nail beds in the fetus [58].

Stress
One last internal exposome factor to explore is stress.While little data are known on how it directly impacts nail health, we know that stress-related conditions, such as anxiety disorder, are associated with different selfinduced nail affections, such as onychophagia, median canaliform dystrophy, and all the other clinical features that belong to the spectrum of onychotillomania [59,60].Furthermore, nail clippings have been used to explore the relationships between stress, sleep, self-control, and levels of cortisol (CORT) and dehydroepiandrosterone (DHEA); indeed, a study by Doan et al. [61] indicated that exposure to stressful events and sleep disturbances were associated with higher levels of nail DHEA, while self-control was associated with higher levels of nail CORT.It seemed that there was no significant relationship between nail CORT and DHEA levels.Academic stressors among adolescents were also found to influence hormone levels, suggesting potential implications for mental and physical health.Although the relationship between the hormone levels and their impact on nails is still unknown, potential damage of cortisol on nails has been reported in patients with Cushing syndrome, who are highly predisposed to onycholysis and paronychia [62], while Muehrcke lines have been reported in a patient with ACTH-dependent chronic Cushing syndrome [63].

External Exposomal Factors Air Pollution
Regrettably, there is a notable absence of studies in the existing literature that specifically explores the influence of air pollution on nail health.Nevertheless, we can generate informed hypotheses about how air pollution might affect nail health by drawing parallels with its effects on the skin [64][65][66].For instance, exposure to air pollutants has been linked to skin discoloration, as seen in cases where heavy metals and polycyclic aromatic hydrocarbons cause pigmentation changes in the skin.It stands to reason that these pollutants could similarly affect the color and appearance of nails, just like it happens with tobacco yellow stains [64,65].Furthermore, the detrimental consequences of air pollution on the skin, such as oxidative stress, may extend to the nails, resulting in increased fragility and weakness.The vulnerability of nails to pollutants could render them more prone to brittleness or fungal and bacterial infections [64,65].
Finally, the compromised barrier function of the skin due to air pollution could have repercussions for the underlying tissues responsible for nail growth.This, in turn, might lead to slower or irregular nail growth, ultimately impacting the overall health and appearance of the nails [64,65].
Water Content and Exposure Water may impair nail health because the nail plate contains approximately 16-18% water with a relatively low lipid content.This makes the nail plate susceptible to water permeation; indeed, it appears that water interacts with the keratin proteins in nails through hydrogen bonding and other mechanisms [67].More specifically, the degree of hydration can affect the structural conformation of keratin.For example, increased hydration may influence the geometry of disulfide bridges and the coiling behavior of keratin molecules, leading to nail softening [3,68].The incidence of brittle nails increases with age, affecting 19% of individuals under 60 years and 35% of those aged over 60 years [69].The hardness of the nail plate in the elderly can be influenced by various factors, including the rate of slow linear nail growth and the level of hydration.Indeed, brittle nails can be exacerbated by repeated cycles of hydration and dehydration, such as those caused by a lifetime exposure to wet work or the overuse of dehydrating agents like nail enamels, nail enamel removers, and cuticle removers.Notably, the first three fingers of the dominant hand are particularly susceptible to this condition.Clinically, brittle nails in the elderly can manifest as onychorrhexis, trachyonychia (Fig. 3a), lamellar onychoschizia, and irregularity of the distal edge of the nail plate, leading to a "Castle battlement appearance" [12,14,68,70].

Radiation
UV radiation (UVR) and microwaves may be other exposomal factors with the potential to harm nails and periungual tissues.In recent years, there has been a growing trend in the use of artificial nails, such as silk wraps, gel, and acrylic nails.Gel manicures, in particular, require UVR for polymerization and drying, offering long-lasting and natural-looking results.These UV nail lamps are readily accessible and are used without much regulation, which has raised concerns about the potential carcinogenic risks.They emit UVR, which falls within the wavelength range of 340-380 nm and are available in both fluorescent and LED varieties, with LED lamps requiring short exposure (from 3 to 5 min, every 2-3 weeks).While the risk is relatively low, the incidence of cutaneous malignancy, including melanoma and squamous cell carcinomas, has been on the rise.UVR exposure is known to be a major contributor to the development of these malignancies.Debate exists regarding the potential carcinogenic risk of UV nail lamps.Some studies suggest that the risk is minimal and equivalent to spending a short time in natural sunlight [71,72], while others argue that UV nail lamps can emit energy levels comparable to outdoor work, recommending sunscreen or protective gloves during nail treatments [73,74].Nonetheless, it is advisable to use a broad-spectrum sunscreen with SPF greater than 30 or protective gloves to minimize the potential risk of cutaneous malignancy [75].Microwave radiation also has the potential to lead to various nail problems, such as transverse ridging and onycholysis.In their research, Brodkin and Bleiberg documented instances of nail damage in restaurant employees who had been exposed to a malfunctioning microwave oven.They highlighted the fact that microwave-induced thermal injury could harm the nail matrix, even in cases where the oven user does not perceive any heat sensation [76].

Traumatisms
Nail trauma is a multifaceted external exposomal factor encompassing a spectrum of nail-related issues.These factors can broadly be categorized into occupational factors, repeated microtrauma, foreign body injuries, and nonoccupational habits, such as nail biting.Occupational factors contributing to nail trauma include acute major trauma, which hinges on the extent of damage to the nail bed.The critical criterion for nail stability is having at least 5 mm of a healthy nail bed distal to the lunula [77].Acute major trauma can manifest as hematoma, lacerations, fractures of the terminal phalanx, denudation of the distal phalanx (nail degloving), and the presence of foreign bodies [77,78].Delayed post-acute traumatic deformities may include conditions like onycholysis, dorsal pterygium, split nail deformities, various nail dystrophies, and hooked nails [77,79].Repeated microtrauma, often due to specific professions, may lead to issues such as koilonychia, fingernail fragility, toenail dystrophy, and onycholysis of mechanical origin.Occupations that involve activities like pottery work or The Effect of the Different Exposomal Factors on Nail Health frequent heavy lifting can be associated with nail trauma due to friction and pressure.Slaughterhouse workers, for instance, may experience unique nail problems, including rectangular onycholysis [77,80].
Vibrating power tools, including pneumatic drills and chainsaws, can lead to nail thickening, brittleness, and eventual nail shedding.Additionally, nail-related trauma due to vibrating power tools can result in Raynaud's phenomenon in the skin [77,81].Nonoccupational factors contributing to nail trauma encompass sports-related trauma, which can affect athletes in various ways.For example, golfers may experience distal splinter hemorrhages in the fingers strongly gripping the golf club.Martial arts practitioners, such as judo and karate enthusiasts, may develop nail issues due to the physical nature of their sports [77,82,83].Musician-related trauma is another nonoccupational factor that can impact on nail health.Musicians, like pianists and guitar players, may experience nail damage due to repetitive movements and friction associated with playing their instruments.This can lead to conditions such as paronychia and onycholysis [77,84].In addition to occupational and nonoccupational factors, nail trauma can also result from the common habit of nail biting, known as onychophagia.Nail biting is observed in both children and adults and is often linked to stress and anxiety.It may present with different features such as a short nail plate with an irregular distal margin, wounds and crusts on the periungual tissues, Beau's lines, and potential melanonychia due to the post-traumatic activation of nail matrix melanocytes.Furthermore, this habit can result in a range of complications, including bacterial and viral infections, tooth damage, malocclusions, and the ingestion of nail fragments, which can lead to infections and other health issues [60,85,86].

Manicures
Manicures, a widely adopted method for expressing one's personal style, can exert a considerable influence on the health of nails that transcends the realm of aesthetics.This impact can be regarded as a significant external exposomal factor leading to nail damage.Nail unit damage, often arising as a common issue, takes various forms due to diverse factors.Neglecting proper nail hydration and resorting to excessive clipping of dry nails, along with overzealous filing and incorrect buffing, can culminate in damage to the nail plate, eventually manifesting as onychoschizia.Artificial nails, particularly acrylics, also pose a notable hazard to the well-being of nails.Inadequate application techniques may inflict harm upon the nail matrix, while an excessive reliance on artificial nails can induce nail thinning and fragility [60,87].A systematic review has uncovered a range of mechanical and traumatic nail disorders that are linked to the utilization of gel nail polish (GNP).These disorders encompass conditions such as pterygium inversum unguis, onychoschizia lamellina, nail plate thinning, and more.The causative factors behind these damages can be attributed to both the processes of applying and removing GNP, as well as the chemical constituents of GNP itself, which, in some cases, include the use of LED-activated photoinitiators [87][88][89].
Another pressing concern involves traumatic onycholysis, a condition often triggered by direct injury, exposure to potent irritants, or allergens.Even the excessive length of either natural or artificial nails can contribute to mechanical trauma, thereby escalating the risk of onycholysis [88][89][90].Brittle nails also feature prominently in the realm of manicureassociated issues.Dehydration of the nail plate, exacerbated by contact with detergents, nail polish removers, and organic solvents, plays a pivotal role in exacerbating this problem.Interestingly, the influence of nail cosmetics, such as nail polish, on water retention is subjected to varying interpretations.While some advocate that nail polish is beneficial in this regard, the use of enamel removers can be detrimental [5,[88][89][90][91].
Allergic and irritant contact dermatitis (ACD/ICD) can also manifest as a result of nail polish, enhancers and other cosmetics that contain substances capable of inducing skin sensitization or irritation.Approximately, 2% of individuals may develop ACD or ICD in response to nail care products [92,93].ACD might develop when exposed to potent sensitizers such as isobutyl, ethyl, and tetrahydrofurfuryl methacrylate.It is also important to note that the cured acrylic, in its polymerized form, does not cause sensitization, only the liquid monomer does [89].
Lastly, nail discoloration, while often temporary, may materialize due to the staining of keratin by nail polish.Leukonychia, characterized by the presence of white spots or bands on the nail plate, can emerge as a consequence of trauma or specific manicuring practices to the nail matrix or nail plate (true leukonychia) (Fig. 3b).Additionally, another variant of leukonychia, known as pseudoleukonychia, is also linked to the use of nail cosmetics, such as artificial nails and the frequent use of nail polish removers (Fig. 3c) [94].

Nails Infections
Nail infections, primarily caused by Gram-negative bacteria such as Pseudomonas aeruginosa, are another possible exposomal element to take into consideration.More than half of the clinical isolates of P. aeruginosa produce blue-green pigments, pyoverdin and pyocyanin.While P. aeruginosa is an opportunistic pathogen that can cause various infections, it rarely infects intact nails; indeed, several predisposing factors are fundamental, including onycholysis, onychotillomania, microtrauma to the nail fold, chronic paronychia, chronic exposure to water, soaps, or detergents, and associated nail disorders like psoriasis (Fig. 3d) [95].There is a connection between fungal and P. aeruginosa nail infections, with fungal infection promoting bacterial colonization [96].More specifically, it has been reported that Candida albicans, a type of yeast commonly found in the human gastrointestinal tract, can colonize the onycholytic space in fingernails, particularly in women.This may be because women who experience recurrent Candida vaginitis (yeast infections in the vaginal area) are more likely to have Candida species in other areas of their bodies, including their fingernails.The presence of Candida in the onycholytic space is not necessarily the primary cause of onycholysis but rather a secondary opportunistic infection; the onycholytic space provides an environment where microorganisms like Candida can thrive, especially when it is moist and warm [97].

Management
Effective management of the effects of exposome on nails involves addressing the underlying causes, when possible, protective measures, topical solutions, and biomineral supplementation [70,91].For what concerns biomineral supplementation, it is important to underscore that nutritional supplements like keratogenic nutricosmeceutics with copper, molybdenum, and manganese aim to enhance and repair fingernails and toenails.Biotin-based supplements are anticipated to improve overall nail health, while supplements comprising zinc, selenium, vitamin C, cysteine, and folic acid are suggested to boost nail growth [70,91,98].Importantly, avoiding exposure to water, detergents, and other irritants is strongly recommended [91].In addition, as discussed earlier, exposomal factors primarily lead to various nail conditions, with nail brittleness being a common outcome.Therefore, advocating for the use of nail moisturizers, nail strength-eners, and nail wrapping can be beneficial in safeguarding and fortifying nails [91,99].Innovative topical strategies might help counteracting deleterious effects induced by exposomal factors.One such solution is the water-soluble nail-strengthening (WSNS) solution, which utilizes hyaluronic acid and Pistacia lentiscus to help strengthen the nail plate.Hyaluronic acid aids in rehydrating the nail and surrounding tissues, effectively combatting the fragility induced by dehydration, whereas P. lentiscus (or Mastic Oil), known for its aromatic resin, stimulates keratin synthesis, enhancing nail thickness and strength, thereby improving nail appearance and growth.An in vitro study comparing WSNS to a marketed product and placebo using bovine hoof membranes showcased a significant increase in firmness with WSNS application [99].Another clinical trial involving 23 female participants with brittle nails demonstrated noticeable improvements in nail weakness and appearance after 3 months of daily use.Patients reported high tolerance and satisfaction with the product's application [100].The WSNS solution stands out due to its unique formulation, offering effective rehydration, stimulation of keratin synthesis, and enhancement of nail appearance and strength.Its water-soluble nature facilitates penetration into periungual tissues and nails, making it ideal for topical use.Moreover, its user-friendly packaging and cosmetic attributes contribute to increased patient adherence and satisfaction.Collectively, evidence from diverse studies supports the efficacy, safety, and convenience of WSNS in improving nail quality [99][100][101].

Conclusions: Take Home Messages and Next Steps
Our nails are impacted by a diverse array of internal factors as age and genetics, as well as exposomal factors, including medications, stress, UV radiation, water exposure, trauma, and manicure practices.These factors can result in a wide range of effects on nail health, with nail brittleness being one of the most prevalent outcomes.It is essential to be aware of these influences and take proactive steps to protect and strengthen our nails.The key takeaway is that understanding and addressing these factors can help maintain healthy nails.Whether through proper nail hygiene, protective measures, or the use of topical solutions, we can enhance our nail health.For the future, further research and collaboration between healthcare providers, researchers, and the beauty industry are necessary to The Effect of the Different Exposomal Factors on Nail Health better understand and mitigate the exposomal effects on our nails.This knowledge can lead to the development of more effective treatments and prevention strategies for a wider range of nail conditions.
Fig.1.Global photography of nail condition due to aging.Koilonychia (a), a condition causing nails to become abnormally thin and concave, often associated with iron deficiency; pincer nails (b), where the edges of the nails curve inward, causing discomfort and potential nail damage; onychogryphosis (c), a condition involving nail overgrowth, often leading to thick, curved, and misshapen nails; and an ingrown nail (d), classically associated with erythema, swelling, and a pyogenic granuloma in the affected area.

Fig. 2 .
Fig. 2. Global photography of nail affections due to internal exposomal factors.Splinter hemorrhage in nails (a), with dermoscopic close-up look (b), characterized by small red or brown streaks under the nails, often associated with trauma.c Muehrcke's lines, transient horizontal white bands that appear in the nail bed and are often associated with various health conditions.d Nail clubbing, a condition where the nails thicken and curve around the fingertips, is often indicative of underlying lung issues or mal-nutrition.e Beau's lines, which are transverse depressions in the nail plate, are often caused by severe illness or trauma that disrupts nail growth.f Onychomadesis, a condition where the nails detach from the nail bed and shed, is usually caused due to a temporary interruption in nail growth.g Paronychia, an inflammation around the nail fold, can be acute or chronic and may lead to pain and swelling.h Nail pyogenic granuloma, a benign vascular tumor occurring near the nail bed.

Fig. 3 .
Fig. 3. Global photography of nails abnormalities due to external exposomal factors.a Trachyonychia, a condition characterized by roughening and surface abnormalities of the nail plate.b True leukonychia, a condition characterized by white discoloration or spots on the nail plate, often due to nail matrix or nail plate damage.c Pseudoleukonychia, associated with whiteness of the nail plate, typically due to exogenous compounds, trauma, or skin diseases.d Pseudomonas infection, a bacterial nail issue often characterized by green and black coloration of the nail plate.

Table 1 .
Summary of the most common nail affections due to internal exposomal factors