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Nail Disorders in Older People, and Aspects of Their Pharmaceutical Treatment

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Nail Disorders in Older People, and Aspects of Their Pharmaceutical Treatment Nail disorders in older people, and aspects of their pharmaceutical treatment Sudaxshina Murdan* UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK *Corresponding author T +44-207 753 5810 F +44-207-753-5942 E [email protected] 1 Abstract The aim of this paper was to explore how aging influences the nail unit, its disorders and its response to treatment, and to identify some of the age-related gaps in the ungual drug delivery literature. Aging causes obvious changes to the nail, some of which are inherently due to old age, while others are due to diseases/conditions which become more prevalent as we age. Alterations in the nail plate’s colour, contour, thickness, fragility, surface features, cell size, chemical composition and growth rate are some of the changes, with toenails and fingernails showing different effects. With respect to disease, the incidence of onychomycosis – the most common nail disorder – is considerably higher in older people. Similarly, brittle nails become more common as we age. In contrast, the literature about ageing and the incidence of nail psoriasis is inconclusive, although, it is clear that as one gets older, the negative impact of nail psoriasis on one’s quality of life decreases. Pharmaceutical treatment of the diseases comprises local and systemic therapies, sometimes in combination. Systemic therapies have the inherent disadvantages of adverse systemic effects, drug interactions and the need for monitoring, disadvantages which are especially problematic for older people who are more likely to suffer from co-morbidities and be on other medications. Topical therapy avoids such disadvantages. However, the success rates of commercially available preparations are low, and older people may need help with their application. It is also proposed that regular inspection and grooming of nails should become part of routine care of older people, as these would provide opportunities to identify and treat any problems at an earlier stage. 2 1. The Nail Unit The nail unit - consisting of the nail plate, the nail bed, the nail folds, the hyponychium and the nail matrix (Fig. 1) - protects the delicate tips of fingers and toes against trauma, enables the sensation of fine touch, is used for scratching, grooming, in self-defence, as a cosmetic organ and a tool [1-13] although ideally it should not be used as a tool to prevent injury. The live nail matrix produces the (dead) nail plate which is firmly held to the nail bed - a very thin epithelium underneath the nail plate. The latter is also supported by the lateral and proximal nail folds which enclose it at its lateral and proximal edges respectively. The dorsal surface of the proximal nail fold is continuous with the cuticle, which adheres strongly to the nail plate surface, creating a physical seal against the entry of exogenous materials. At the distal edge of the nail plate is the hyponychium, which is the region underneath the free edge of the nail plate where the nail plate starts to separate from the nail bed. The whole nail unit is anchored in place by attachment to the distal phalanx, and is well perfused by blood and lymph, and has a rich nerve supply [1-11]. All of these components of the nail unit may be involved in nail disease, although due to the fact that the nail plate is the one that is most associated with the nail unit (and is commonly called the nail) and shows the most obvious changes upon aging and in disease states, it receives the most attention by lay and medical people alike. The nail plate grows throughout life at, on average, 3mm per month (fingernail) and 1.5-1 mm per month (toenail) [2]. Thus, generally fingernails grow out completely in six months and toenails in 12-18 months, rate of growth being influenced by many factors such as gender, age, pregnancy, disease, nutrition, etc. Fingernail plates are also thinner (0.5mm 3 at the distal edge) than the big toe (up to 1 mm at the distal edge) [14]. The nail plate is transparent, but usually appears pink which is imparted by the capillary network in the nail bed. It is hard, yet slightly elastic and is curved in both the longitudinal (in the direction of growth) and transverse (perpendicular to the direction of growth) directions. Its size, shape, thickness, surface ridging, curvature, and mechanical properties such as flexibility vary greatly within and among individuals, with site (finger/toe), and other endogenous and exogenous factors such as disease states and seasons. It is made up of three (or two according to some researchers [15]) distinct parallel strata: dorsal, intermediate and ventral [16-18], and consists of 80-90 layers of dead, flattened, keratinised cells and an intercellular ‘cement’ (thought to consist of proteins and/or mucopolysaccharides [4]) between the cells. Keratin forms the main bulk of the nail plate [19, 20], followed by water (at 5%-30%, [21, 22]), lipids (less than 5% w/w in adults) [20, 23], and small amounts of elements such as calcium, magnesium, sodium, potassium, iron, copper, zinc, aluminium, chlorine, selenium, fluoride [24, 25]. 2. Nail changes and diseases/disorders in older people Nail disorders can affect all ages, from totally or partially absent nail plates in newborns to severely distorted nailplates in older people. Nail disorders can be benign, such as change in colour, to extremely serious, such as tumours which require surgical removal, and others which may not seem so severe, but are long-term, recalcitrant to treatment and affect patients physically and emotionally. Symptoms include swollen and inflamed nail folds and nail plates that are over- or under- curved, excessively thickened/hard/soft/friable/ridged longitudinally or transversely, covered in pits (shallow depressions in the nail plate) and 4 detached from the nail bed. These symptoms may be caused by a variety of factors, such as chemicals (including medicinal drugs), infections, trauma, and congenital, hereditary, systemic and local diseases, and can affect all or only some of the components of the nail unit. Aging causes obvious changes to the nail, some of which are inherently due to old age, while others are due to other diseases/conditions which become more prevalent as we age, such as diabetes, reduced immunity, impaired peripheral blood circulation, trauma and abnormal biomechanics [26-28]. An obvious change upon aging is the nail plate’s colour, from pale pink to yellow, grey or white, with a dull, opaque appearance. Some older individuals present ‘Neapolitan’ nail plates which show no lunulae, a white proximal portion, a normal pink central band and an opaque distal free edge [29]. Nail plates with multiple transverse white bands or longitundinal dark bands have also been reported [30, 31]. Histological examination has revealed an increase in the size (area) of nail plate keratinocytes [32, 33], and an increase in the number of pertinax bodies (remnants of keratinocyte nuclei) [34]. The nail plate’s chemical composition is also altered, with increase in carbon and decrease in nitrogen contents with aging [35]. While there is no significant change in the total lipid content, the proportions of the different lipid fractions making up the total lipid content become more variable with advancing age [23]. In the nail bed, there is thickening of the blood vessels and degeneration of elastic tissue [34]. 5 Upon aging, nail plates also grow at a slower rate [14, 36], which may be an excellent evolutionary response as some older individuals experience problems cutting their finger- and toe- nails due to poorer eyesight and reduced manual dexterity and flexibility needed to groom one’s nails, especially the toenails. The problems with cutting one’s toenails may be compounded by the fact that toenails thicken with age [37]. The toenail may also curve sideways as it thickens, appearing as a ram’s horn dystrophy (called onychogryphosis) [38]. Ingrowing toenails are also a common problem in older people [38]. Trauma to the toes or poorly fitting shoes can also result in subungual hematoma in elderly patients, especially those on anticoagulant therapy [38]. In contrast to the toenail, the fingernails, in general, become thinner with age [37], and less curved in both the longitudinal [27, 28] and transverse directions [39]. There is increased longitudinal ridging in the nail plate, which may lead to splitting at the distal ends, and subsequently interfere with daily activities [34]. Horizontal peeling of layers of the fingernail plate at the distal end is also common. The incidence of brittle nails, characterized by increased fragility of the nail plate, also increases with aging, with 19% of people under 60 years old versus 35% of those aged 60 or over reporting brittle nails [40]. There is a considerable influence of sex however, with the influence of age being more marked in males; 12% of younger males (< 60 years old) reported brittle nails compared to 31% of those aged ≥ 60 years, while, 29% of younger females (< 60 years old) reported brittle nails compared to 36% of those aged ≥ 60 years [40]. It is not known exactly what causes brittle 6 nails, although they are associated with repeated exposure to water and certain chemicals, excessive use of nail cosmetics and cosmetic removers and aggressive manicuring [41]. In the general population, the most common nail disease is onychomycosis (fungal infections of the nail plate and/or nail bed) which accounts for up to 50% of all nail disorders [38]. Onychomycosis affects both finger and toe nails, although toenail infection is more common and more recalcitrant to treatment, and males are more commonly affected than females [42]. The great majority of toenail infections are caused by dermatophytes, especially Trichophyton rubrum, followed by non-dermatophyte moulds and Candida, while fingernail infections are mainly caused by yeast [42, 43].
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