The Skin of the Neonate

Development of the Appendages

The appendages derive from embryonic invaginations of epidermal germinative buds into the dermis. They include hair, sebaceous glands, apocrine glands, eccrine glands, and nails. The arrector pili muscle is attached to the hair follicle. Lanugo (i.e., fine, soft, immature hair) frequently covers the scalp and brow of the premature infant. The scalp line may be poorly demarcated, and lanugo also may cover the face. Scalp hair is usually somewhat coarser and matures earlier in dark-haired infants.

The growth phases of the hair follicle are usually synchronous at birth. Eighty percent of the follicles are in the resting state. During the first few months of life, the synchrony between hair loss and regrowth is altered so that 20% of scalp hairs are growing in the same phase at the same time. Hair may become coarse and thick, acquiring an adult distribution, or there may be temporary alopecia.

There are sex differences in hair growth; boys’ hair grows faster than girls’ hair. In both sexes, scalp hair growth is slower at the crown. The normal pattern of hair growth is disturbed in many chromosomal disorders. Evidence supports a genetic link between the formation of clockwise posterior parietal hair whorls and specific (right) handedness of the individual. This finding supports an unexpected association between gene-based hair patterning and human brain development that warrants further substantiation. Supporting the significance of the skin–brain connection, evidence has shown the human hair follicle can synthesize cortisol de novo and is a functional equivalent of the hypothalamic-pituitary-adrenal axis.

The eccrine sweat glands are coiled structures that form during the first trimester as a downgrowth from epidermal cellular clones. No new glands are formed after birth. They are distributed over the entire body surface and are innervated by sympathetic cholinergic nerves. During the first 24 hours of life, term infants usually do not sweat; on approximately the 3rd day, sweating begins on the face. Palmar sweating begins later. Thermal sweating as a function of body or environmental temperature should be distinguished from emotional sweating associated with crying or pain. The latter is best assessed on the palms and soles.

The sebaceous glands differentiate primarily from the epithelial portion of the hair follicle at approximately 13-15 weeks of life and almost immediately produce sebum in all hairy areas. The glands develop as solid outpouchings from the upper third of the hair follicle. These solid buds become filled with liquid centrally where the cells disintegrate; acini and ducts develop, opening most frequently into the canals between the hair follicle wall and hair shaft. Ectopic glands occur occasionally on the lips, buccal mucosa, esophagus, and vagina.

Surprisingly little is known about the regulation of the rapid growth and activity of sebaceous glands up to and immediately after birth. Hypothetically, secretion by the fetal adrenal gland of weak androgens such as dehydroepiandrosterone (DHEA) is followed by intra-sebocyte conversion to testosterone and production of products of the pilosebaceous unit such as vernix caseosa. This hypothesis remains to be fully tested, but it has the singular advantage of functionally integrating two disparate and unexplained facts; that is, the mutual hyperplasia of the sebaceous gland and the adrenal cortex during the latter half of gestation in the human fetus. Androgens are the only hormones that unequivocally have a stimulating effect on the sebaceous glands; estrogens depress their growth. Between 2 months and 2 years, the sebaceous glands of the normal infant begin a period of quiescence that lasts until puberty.

The apocrine glands are relatively large organs that originate from and empty into a hair follicle. Embryologically, they develop somewhat later than the eccrine glands. Apocrine development is advanced by 7 or 8 fetal months, when the glands begin to produce a milky-white fluid containing water, lipids, protein, reducing sugars, ferric iron, and ammonia. In the newborn, the acini are well formed. The biologic function of the gland is unknown in infants, but it is related to pheromone production in other animal species.

Vernix Biology

Vernix caseosa, a unique material that coats the fetal skin surface during the last trimester of pregnancy, contains lipids of sebaceous origin as well as numerous water-laden fetal corneocytes. A growing body of evidence supports the hypothesis that vernix caseosa participates in regionally “waterproofing” the skin surface, thereby allowing cornification to occur, initially around the hair follicles and then over the interfollicular skin. A better understanding of vernix caseosa and fetal sebaceous gland physiology is biologically relevant and may be applicable to care of the very low birth weight infant and to clinical situations in which the epidermal surface is inadequately developed, burned, or traumatized.

Physiologically, vernix is a hydrophobic material containing wax esters, cholesterol, ceramides, and squalene in addition to other minor lipid components. Vernix has high water content (≈80%), with the water primarily distributed within flat, polygonal, cornified squames. As term approaches, vernix detaches from the fetal skin surface under the influence of pulmonary surfactant and is swallowed by the fetus. In close analogy to breast milk, vernix contains multiple molecules associated with the innate immune system, including lysozyme, lactoferrin, and defensins, as well as antioxidants such as alpha tocopherol. Vernix possesses both emollient (moisturizing) and cleansing functions. Thus, at birth, the human infant is covered with a complex material possessing endogenous anti-infective, antioxidative, moisturizing, and cleansing capabilities. Extreme prematurity, as well as postmaturity, is associated with diminished vernix on the skin surface at birth.

Blood and Lymphatic Vessel Development

The vascular network supplying the skin develops in early embryonic life from the mesoderm. In 60- to 70-day-old fetuses, there are two vascular networks: a superficial one that appears to correspond to the subpapillary plexus of adult skin and a deeper network that represents the deep reticular vascular network of adult skin. New capillary beds organize to supply the developing epidermal appendages from the 5th month of gestation. These two networks persist into the newborn period; however, the arrangement of vessels remains unstable for the first year of life, and further organization of the vascular network occurs postnatally.

Vasomotor tone is controlled by a delicate and complex series of neural and pharmacologic mechanisms that involve the sympathetic nervous system, norepinephrine, acetylcholine, and histamine, and may involve serotonin, vasoactive polypeptides, corticosteroids, and prostaglandins. The physiologic requirements of skin vary considerably; skin blood flow ranges from 0.1-150 mL/mm ² of tissue per minute.

Development of Cutaneous Innervation

The nerve networks in the dermis develop at a very early embryologic age and appear to be distributed in a random fashion. The most superficial nerves have the smallest diameter and are the least myelinated. In addition to the dermal nerve network, which may show considerable regional variation, nerve fibers may serve particular regions or structures such as hair follicles, eccrine glands, arrector pili muscles, and the subepidermal zone. Superficial nerves conduct mechanosensory stimuli from the specialized Merkel cells within the epidermis. The sebaceous glands are not innervated.

Special neurologic structures include a dense perifollicular nerve network with exquisite tactile sensory properties and mucocutaneous end organs highly concentrated in erogenous zones. Meissner tactile organs are found in newborn skin as undeveloped structures that mature after birth. Merkel corpuscles probably govern two-point tactile discrimination on palms and fingertips; they are disk-shaped terminals that are seen during the 28th week of fetal life. After birth, these receptors undergo little alteration. Vater-Pacini corpuscles are found around the digits, palms, and genitals; they are fully formed and numerous at birth.

The arrector pili muscles are innervated by sympathetic nerves, and norepinephrine acts as the neurotransmitter. The eccrine glands are innervated by sympathetic fibers, but acetylcholine acts as the neurotransmitter. Parasympathetic fibers may accompany the sensory nerves in the vessel walls and cause vasodilation. The axon reflex is poorly developed in the newborn; in the neonate of low birth weight, axon reflex sweating may be difficult to elicit.

Sebaceous Gland Hyperplasia and Milia

Approximately 8% of infants have multiple, white, 1-mm cysts (i.e., milia) scattered over the cheeks, forehead, nose, and nasolabial folds. These milia may be few or numerous, but they frequently occur in clusters. Milia are often confused with the more common condition of sebaceous gland hyperplasia (43% of infants), which manifests as smaller, flatter, more yellow dots seen on the midface as well ( Fig. 94.3 ). Histologically, milia are keratogenous cysts similar to Epstein pearls, which are distributed along the midpalatal raphe. Bohn nodules are cysts that occur on the palate and the buccal and lingual aspects of the dental ridges and represent remnants of mucous gland tissue. Intraoral lesions are found in 75%-80% of newborns. Because all these cysts exfoliate or involute spontaneously within the first few weeks of life, no treatment is required.

Pigmentary Lesions

The most frequently encountered pigmented lesion is the mongolian spot (dermal melanosis), which occurs frequently in African-American, Asian, and Native-American infants and infrequently in white infants. Although most of these lesions are found in the lumbosacral area, occurrence at other sites is not uncommon. The pigmentation is macular and gray-blue, lacks a sharp border, and may cover an area 10 cm or larger in diameter. Pigmentary lesions result from delayed disappearance of dermal melanocytes.

Most of these lesions gradually disappear during the first few years of life, but aberrant lesions in unusual sites are more likely to persist. Because of their distinctive color and morphology, mongolian spots are not easily confused with congenital pigmented melanocytic nevi or café au lait spots, which often have their onset later in infancy or in early childhood, although they may be present at birth.

Rarely, extensive mongolian spots may be associated with inborn errors of metabolism (Hurler syndrome, GM1 gangliosidosis, mucolipidosis) and neurocristopathies.

Nevus Simplex or Salmon Patch

The nevus simplex is the most common neonatal cutaneous lesion and is present in up to 80% of normal newborns ( Fig. 94.4 ). These lesions blanch when compressed and are usually centrally located and symmetric, appearing on the nape, the eyelids, and the glabella. In a prospective study of affected infants, most of the facial lesions had faded by 1 year of age, but those on the neck were more persistent. Surveys of adult populations confirm the persistence of the nuchal lesions in approximately one-fourth of the population.

Harlequin Color Change

Harlequin color change is a transient phenomenon observed in the immediate neonatal period and common in the low birth weight infant. The dependent side of the body becomes intensely red, and the upper side pales, with a sharp midline demarcation. The peak frequency of attacks in one series occurred on the 2nd, 3rd, and 4th days, but episodes were observed during the first 3 weeks of life. These episodes are of no pathologic significance. They have been attributed to a temporary imbalance in the autonomic regulatory mechanism of the cutaneous vessels; there are no accompanying vital sign changes.

Erythema Toxicum

Erythema toxicum is a benign and self-limited eruption that usually develops at 24-72 hours of age, but new lesions may appear until 2-3 weeks of age. The disorder is more common in term than premature infants, which suggests that it may represent an inflammatory reaction requiring mature skin. These lesions may vary considerably in character and number; they may be firm, 1-3 mm, pale yellow to white papules or pustules on an erythematous base resembling flea bites or erythematous macules as large as 3 cm in diameter. Individual lesions are evanescent, often lasting only a matter of hours. They may be found on any area of the body but occur only rarely on the palms and soles. They are asymptomatic with no related systemic involvement and the cause is unknown, although a variety of specific cytokines have been implicated in the pathogenesis. A microscopic examination of a Wright- or Giemsa-stained smear of the pustule contents demonstrates numerous eosinophils; Gram stains are negative for bacteria and cultures are sterile. No treatment is necessary because spontaneous resolution occurs in 6 days to 2 weeks.

Transient Neonatal Pustular Melanosis

Transient neonatal pustular melanosis is a distinctive eruption that heals with brown pigmented macules. It consists of three types of lesions: first-stage lesions are small superficial vesiculopustules with little or no surrounding erythema. These rapidly progress to the second stage, which consists of collarettes of scale or scale crust surrounding a hyperpigmented macule (third stage) ( Fig. 94.5 ). All three types of lesions may be present at birth, but the macules are observed more frequently. The lesions may be profuse or sparse and occur on any body surface, including the palms, soles, and scalp. Sites of predilection are the forehead, submental area and anterior neck, and lower back. When intact pustules rupture, a pigmented macule often is discernible central to the collarette of scale, which represents the margin of the unroofed pustule. Presumably, the macules result from postinflammatory hyperpigmentation, and those present at birth may be the sequelae of in utero pustular lesions.

Pustular melanosis may be confused with erythema toxicum, congenital cutaneous candidiasis, or staphylococcal pyoderma. Cultures and Gram stains of smears prepared from intact pustules are devoid of organisms; Wright stains of intralesional contents demonstrate cellular debris, polymorphonuclear leukocytes, and a few or no eosinophils, in contrast to those of erythema toxicum. Although the pustules disappear in 48 hours, the hyperpigmented macules may persist for as long as 3 months. These lesions require no therapy as the disorder is benign and transient.

Miliaria

Miliaria is an eruption characterized by crops of superficial vesicles resulting from eccrine sweat gland duct obstruction leading to sweat retention. The three types of lesions are superficial thin-walled vesicles without inflammation (i.e., miliaria crystallina, Fig. 94.6 ); small, erythematous, grouped papules (i.e., miliaria rubra); and nonerythematous pustules (i.e., miliaria pustulosis or profunda). The eruption most frequently develops in the intertriginous areas and over the face and scalp. It is exacerbated by exposure to a warm and humid environment. Miliaria sometimes can be confused with erythema toxicum; rapid resolution of the lesions when the infant is placed in a cooler environment differentiates them from other causes of infectious pustulosis. A Wright-stained smear of vesicular lesions demonstrates only sparse squamous cells or lymphocytes, permitting exclusion of infectious vesicular eruptions. No topical therapy is indicated.

Neonatal Acne and Infantile Acne

Neonatal acne occurs in up to 20% of newborns and is more commonly seen in boys. Increased sebaceous secretions secondary to maternal and neonatal androgens and colonization of the sebaceous glands by the yeast Malassezia furfur are implicated in its pathogenesis and are characterized by small red papules and pustules on the face during the first weeks of life. Unlike in adolescents, comedones and cysts are usually absent. The lesions are asymptomatic and resolve spontaneously without scarring over several weeks. The clinical significance lies in differentiating this rash from infections, excluding virilization as its underlying cause and potential implication of severe acne in adolescence.

Infantile Acropustulosis

Infantile acropustulosis is characterized by recurrent crops of pruritic, sterile vesiculopustules with a predilection for the palms and soles. The lesions appear in crops every 2-3 weeks and last 7-10 days. They involve the hands and feet primarily, but occasionally may involve the limbs as well. Because of the distribution, it is often confused with scabies. It is more common in African-American and male infants. The condition resolves spontaneously. A subcorneal pustule filled with neutrophils is seen on skin biopsy. Traditional therapy consists of topical steroids and antihistamines, although one report indicates successful treatment with topical maxacalcitol, an active form of vitamin D3. A recessive mutation in the gene coding interleukin 1 receptor antagonist has been described in a case of infantile pustulosis treated successfully with recombinant human interleukin 1 receptor antagonist anakinra.

Disorders of Cornification: The Scaly Baby

The most common and benign causes of excessive scaling are due to physiologic desquamation (normal term infants) and dysmaturity (post-mature and small for gestational age infants), neither of which have long-term sequelae. Less common causes include the congenital ichthyoses and the ectodermal dysplasias (particularly hypohidrotic ectodermal dysplasia), all of which are chronic, heritable disorders.

Physiologic Desquamation and Dysmaturity

The gestational age of a newborn with accentuated physiologic desquamation usually is 40-42 weeks; peak shedding occurs near the 8th day of life. These infants are otherwise normal in physical appearance and behavior. In contrast, the dysmature infant (see Chapter 22 ) has distinctive characteristics. The body is lean with thin extremities and decreased subcutaneous fat. The ponderal index is low with diminished body weight in relation to length. The skin is often scaly with parchment-like desquamation, especially of the distal extremities. There is often meconium staining of the skin as well as the nails and umbilical cord. The hair is abundant and the nails are abnormally long. In the normal infant with accentuated physiologic scaling and the dysmature infant, desquamation is a transient phenomenon, and the integument continues to serve its intended protective function. In contrast, the infant with congenital ichthyosis may have serious difficulties early in life because of impaired barrier function and the subsequent risks of secondary infection.

Ichthyoses

The term ichthyosis derives from the similarity of the skin condition to the scales of a fish. It refers to a complex and often confusing plethora of conditions characterized by disorders of cornification with or without systemic symptoms. In 2010, a consensus conference of experts developed a new classification that was clinically based and easily comprehensible by clinicians. It was broadly divided into nonsyndromic (restricted to skin) and syndromic (skin plus other organs). Ichthyosis in the newborn period may manifest as scaling only, scaling and erythroderma, a collodion membrane, or the thickened plates of harlequin ichthyosis. Although rare, it is important for the neonatal caregiver to recognize the patient with ichthyosis as the barrier function of the skin is often compromised. Prompt management and diagnosis can be lifesaving. Selected conditions with particular relevance to the newborn are highlighted below, followed by a general overview of treatment strategies. Table 94.3 lists the major clinical phenotypes of the ichthyoses in the newborn period.