Labial epidermis

The epidermis of the vermilion region is twice as thick (180 μm) as the adjacent skin [5, 8, 9]. It still has the markers of cutaneous epidermis differentiation, even though it has fewer keratinized layers than the skin [10]. Barrett et al. [5] found that the distribution of cytokeratins (CK) differed from that of the intermediate zone, with a loss of the skin cytokeratins CK1 and CK10 and the presence of the mucosal cytokeratins CK4, CK13, and CK19. CK5 and CK14 were still present in the basal layer and occasionally in the suprabasal layer. CK8, CK18, and CK20 were found only in Merkel cells. Involucrin was present in all the zones, but its restricted distribution in the stratum granulosum of the skin extended to the stratum spinosum and the parabasal keratinocytes of the lip zone and the mucosa. Loricrin, profilaggrin, and filaggrin were found in the stratum granulosum of the orthokeratinized zones but not after the junction between the vermilion zone and the intermediate zone.

The corneocytes in the mucosa are flat, smooth cells. In contrast, most of the corneocytes on the surface of the vermilion are seen to have microvilli on all their internal surfaces when examined under the high‐power microscope [11]. These projections are rarely seen on the corneocytes of the adjacent skin [12]. The cell turnover of the epidermis of the vermilion seems to be more rapid than that of the adjacent skin cells. The vermilion also appears to lose water three times as faster than the cheeks and to have a lower conductance. Thus, the lips function as a barrier but their capacity to retain water is much poorer than that of facial skin [2, 13, 14].

Hikima et al. [12] showed that the surface of the lips, like the surface of the skin, has cathepsin D‐like activity and chymotrypsin‐like activity. These enzymes are involved in the hydrolysis of corneodesmosomes, and hence in the release of corneocytes from the skin surface. Lipid repartition is different between vermilion and skin, with a higher concentration of docosahexaenoic acid in the vermilion [15].

Like the skin, the vermilion epithelium contains melanocytes and there is melanin in the cytoplasm of basal cells [5]. However, as the melanin pigmentation is light and associated with reduced keratinization, the color of the hemoglobin is seen more clearly. There are also Langerhans cells in this zone [9]. Cruchley et al. [16] used immunodetection of CD1a to show that there were more Langerhans cells per unit area of the lips than in abdominal skin.

Sallette et al. [17] showed that there is more neuropeptide‐type neurotransmitter in the epidermis of the lips than in the eyelids, which seems to indicate that the lips are better innervated.

Lip dermis and lamina propria

The epithelium of the vermilion lies on a layer of connective tissue, which ensures the continuity of the cutaneous dermis and the lamina propria. This tissue is mainly composed of collagen fibers and a network of elastic fibers in a hyaluronan gel.

There is a thin layer of fatty tissue between the muscle and the dermis in the cutaneous part of the lips with many attachments between the muscle and the skin [18]. The deep part of the lamina propria of the mucosa lies above the hypodermis of the subcutaneous zone. The invaginations at the junction between the epithelium and the connective tissue of the vermilion are higher than those of the skin [19]. These papillae contain blood capillaries. The capillary loops in the vermilion are higher than those of the skin, which accentuates the red color of the lips due to the presence of hemoglobin in them [20].

The lymph drainage of the red border is not uniform; it flows toward the cutaneous system on the external side of the lips and toward the mucosal system on the inner side [21].

Lip topology

The description of lip topology first interested legal medicine because each individual has a different organization, much like fingerprints [22]. The study of lip prints is called cheiloscopy. The development of kiss‐proof lipsticks led legal medicine to develop protocols for revealing latent prints at a crime scene [23]. Lip prints can be classified in several ways and their distributions in populations have been quantified [24–27].

Sensitivity of lips to the environment

As the lips have little cornified tissue or melanin they are very sensitive to chemical, physical, or microbial damage. Their prolonged exposure to sunlight, particularly for fair‐skinned people, may lead to the appearance of actinic cheilitis and even spinocellular carcinoma [28]. Most lip cancers, considered as mouth cancers, are most common on the lower lip. They are squamous cell carcinomas, beginning in the cells in the middle and outer layers of the epidermis called squamous cells. Pogoda and Preston‐Martin [29] suggested that frequent applications of sunscreen can have a positive protective effect. Smoking has also been found to be a major risk factor for lip cancers.

Aging of the lips

The aesthetic consequences of aging of the superficial lip tissues (sagging, distension, and ptosis) are aggravated by changes in the shape of the bone and dental infrastructure and the aging of the underlying muscles and adipose tissue. The orientation of the labial aperture changes with a drooping of the lateral commissures: from a concave curve in new‐borns and children to a horizontal line in adults, and then to an inverted curve in the elderly. In profile, the lips, particularly the lower lip, recedes with age. The upper lip becomes lower and enlarged [4, 27, 30]. Tissues become less extensible and elastic because of repeated mechanical stresses and the weakening of the orbicularis orbis muscle with age [4, 30].

The vermilion becomes larger, longer, and thicker at the corners of the mouth [3]. While wrinkles develop in the skin around the lips with age, the outline of the lips themselves becomes sunken [27]. The depth and organization of the relief of the lips vary greatly from one person to another and some young people have deep furrows. Both the spatial resolution and the tactile sensitivity of the lips decrease with age [4, 7, 31, 32]. There may also be histologic signs of solar elastosis. The superficial microcirculatory network (both papillary and mucosal) may become smaller and less dense (reticular and mucosal) [33], together with an apparent thinning of the lips in older people who have lost their teeth [19].

Cosmetic surgery can be used to “refresh” and to fill the tissue to rejuvenate the lips. This might involve reducing the upper lip or recovering the shape of a young lip by a series of interventions to reinforce the shape and projection of the lips and restructure the Cupid’s bow, better define the lip outline, and lift the corners of the mouth. This surgery is accompanied by a rejuvenation of the perioral region, including removal of perioral wrinkles, peeling, laser resurfacing, and dermabrasion [3034–37].

Lip plumpness and cheilitis

Chapped lips are characterized by cracking, fissuring, and peeling of the skin of the lips, and are one of the most common types of cheilitis. Cheilitis are often found in children sucking and chewing on the lower lip. Actinic, exfoliative, angular, eczematous, infectious cheilitis ae the main types recognized. They can be caused by a cold or dry environment, overexposure to ultraviolet radiations, repeated pressure on the lips – as it can develop in players of wind instruments – or by defective dental work. It can also occur in people taking oral drugs, or from a lack of dietary vitamin B₁₂ (riboflavin), B₆ (pyridoxine), nicotinic acid, folic acid, or iron [38].

Hikima et al. [12] reported that the corneocytes at the edges of dried out lips become flattened and their surface area increased. This suggests that the turnover of these cells is slowed in dried out lips. The degree of visible dryness is also correlated with a reduction in cathepsin D, one of the enzymes involved in desquamation, but the chymotrypsin‐like activity remains unchanged.

The upper lip seems to dry out less than the lower lip as it is less exposed. While the hydration measured by the capacitance does not seem to change with age, the loss of water via the lips decreases [31]. Clinically assessed drying out increases with age [27] or is maximum in the thirties [14] according to different studies.

Defects of lip pigmentation

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