Newborn Skin Development: Structure and Function

Epidermis

The epidermis derives entirely from ectoderm. A single-layered epithelium spans the embryo from gastrulation. Subsequent development proceeds in discrete stages: embryonic (5 to 8 weeks) and embryonic/fetal transition (9 to 10 weeks) and then to the early (11 to 14 weeks), mid (15 to 20 weeks), and late (20 weeks–birth) fetal periods. Differentiation and formation of appendages occur predominantly during the second trimester. It is during the late fetal stage that the skin first becomes functional. The stratum corneum, or outer epidermis, has been likened to “bricks and mortar.” Epidermal keratinization begins first on the head, face, and palms. Anucleate corneocytes flatten and form “bricks,” while a mixture of cells, adhesion proteins, and lipids form the semipermeable mortar. One such protein, filament aggregating protein, or filaggrin, has recently been linked to atopy. Patients with filaggrin mutations are at greater risk for eczema, asthma, and allergies. Decreased ability to retain moisture with resulting fissures in the stratum corneum may promote epicutaneous allergen exposure and sensitization. Emerging evidence suggests that early aggressive application of thick emollients to at-risk infants decreases their chance of developing atopic dermatitis.

Dermoepidermal Junction

The DEJ is the interface between basal layer keratinocytes of the epidermis and the dermis and helps the skin resist shearing forces. The critical elements of the DEJ form by 8 to 10 weeks’ gestation. The DEJ is composed of hemidesmosomes, anchoring filaments, anchoring fibrils, and type VII collagen, which combine to tether the dermis to the epidermis ( Fig. 91.1 ). Epidermolysis bullosa (EB) is an inherited disorder of cutaneous fragility that results from defective proteins in this complex. The type of EB depends on the affected protein, and outcomes can vary widely.

Dermis and Subcutis

The dermis is derived from diverse tissue types. Embryonic mesenchymal cells capable of becoming multiple cell types are enmeshed in a hyaluronic matrix called a cellular dermis . At 8 weeks’ estimated gestational age (EGA), the dermis is distinguishable from underlying tissue. By 15 weeks, collagen fibers accumulate, and by 22 to 24 weeks, elastin fibers are first detectable by electron microscopy. Immature dermis will not scar when traumatized (e.g., with a fetal skin biopsy), whereas the increasing tensile strength that accompanies maturation also connotes potential to scar; this occurs at roughly the end of the second trimester. Blood vessel plexi are discernible by 12 weeks’ EGA but do not fully mature until after birth. Vasculogenesis, the formation of endothelial cells and then vessels from angioblasts, is completed by 20 weeks’ gestation; angiogenesis follows as existing vessels give rise to new ones. Sprouting angiogenesis may add new vessels to tissue previously lacking vascularity; this involves spouts of endothelial cells growing toward an angiogenic stimulus, such as vascular endothelial growth factor or basic fibroblast growth factor. Intussusceptive angiogenesis is characterized by a splitting process whereby the vessel wall invades the lumen, causing the vessel to divide in two. This type of angiogenesis occurs only in areas of preexisting vascularity. Both types of angiogenesis can occur in virtually all tissues and organs. Neural networks develop toward the end of the first trimester and follow a vascular pattern. Adipose tissue develops beneath the dermis, starting in the second trimester.

Goltz syndrome (focal dermal hypoplasia) is an X-linked dominant disorder caused by mutations in PORCN . Ninety percent of affected individuals are female and manifest with striking linear atrophic plaques with distinctive fat herniation due to dermal atrophy.

Appendages

Hair, nail, sweat gland, and apocrine gland development relies on coordinated dermal–epidermal interaction that commences around 10 weeks’ gestation. Hair follicle formation, which directs overlying epidermal basal cells to aggregate in the form of a placode, is initiated in the dermis. Hair follicles differentiate during the second trimester, and hair canals are formed by 20 weeks’ EGA when scalp hairs are just visible. Hairs cycle between growth (anagen), resting (catagen), and shedding (telogen). The first shedding cycle occurs around 28 weeks’ gestation, after which they reenter the anagen phase. The final shedding phase generally occurs postnatally, at the occiput, leading to occipital alopecia that often is misattributed to pressure or friction.

Nails begin development at 8 weeks’ EGA, slightly earlier than the hair follicles. A keratinized nail has completely covered the nail plate by 5 months’ EGA. Hair and nail keratins have greater structural integrity than those in the epidermis.

Sebaceous glands develop contemporaneously with hair follicles. At 13 to 16 weeks’ EGA, characteristic sebaceous gland bulges can be seen with hair follicles, just above the insertion of the arrector pili muscle. Maternal hormones induce sebaceous gland production of sebum during the late second and third trimesters. Sebum and shed corneocytes form vernix, which progressively coats the fetus in a cephalocaudal orientation. Fetal lung maturity parallels sebaceous gland activity, and increased physiologic concentrations of surfactant emulsifies surface vernix.

Palmoplantar eccrine sweat glands begin to develop at 55 to 65 days’ gestation and are fully developed by the second trimester. Interfollicular sweat glands and apocrine glands do not form until the middle of the second trimester. Ectodermal dysplasias are a heterogeneous group of disorders with striking abnormalities in skin appendages. Hydrotic ectodermal dysplasia, or Clouston syndrome, is due to mutations in GJB6 (connexin 30), which directs formation of gap junctions found notably in adnexal structures.

Specialized Skin Cells

Melanocytes, Langerhans cells, and Merkel cells comprise the primary epidermal immigrant cells. Melanocytes derive from the neural crest and migrate along Blaschko lines to populate the entire fetal epidermis. Melanocytes are first identifiable at 50 days’ EGA and are fully present at birth, but melanogenesis continues such that skin is not fully pigmented at birth and will darken in the first months. Blaschko lines are distinct from dermatomes, and clinical abnormalities in this distribution can be helpful diagnostically ( Fig. 91.2 ). Incontinentia pigmenti, an X-linked dominantly inherited gene dermatosis due to mutations in NEMO , presents with a series of cutaneous findings over time, first vesicles and then a warty hyperkeratotic phase, followed by dyspigmentation all along Blaschko lines. Knowledge of this pattern can help discriminate from fundamentally different processes, such as herpes zoster, which would present with vesicles in a dermatomal distribution.

Langerhans cells first appear at 40 days’ gestation and serve as antigen-presenting cells. Merkel cells appear at 8 weeks' gestation and serve a mechanoreceptor function.