Sheila S. Galbraith
NEONATAL SKIN DEVELOPMENT AND PHYSIOLOGY
The skin of a newborn infant differs from adult skin in several ways that place infants at increased risk for thermal instability, skin damage, percutaneous infection, and percutaneous toxicity from topically applied agents. The neonatal body surface area-to-weight ratio is up to 5 times greater than that of an adult, and the thickness of infant skin is 40% to 60% less.1 Attenuated rete ridges, formed from comparatively fewer stem cells at the basal layer, provide a relatively limited area of surface attachment to an immature dermis, resulting in relative skin fragility. Sebaceous glands are hypertrophic for several weeks after birth, under the influence of fetal and maternal androgens, but eccrine function does not mature until after term, placing newborns at risk for hyperthermia with overbundling. The vernix caseosa is composed of sloughed keratinocyte and sebaceous gland lipids, with a higher proportion of glandular lipids in boys.
The most clinically significant difference between the skin of a premature and that of a term infant is the barrier function of the most superficial layer of the epidermis, the stratum corneum. Infants born before 32 weeks of gestation have a very thin stratum corneum. Although even in premature neonates, the stratum corneum matures within 2 weeks after birth, premature infants suffer from significant transepidermal water loss with associated hypothermia and fluid and electrolyte disturbances. These problems are proportional to the degree of prematurity. Transepidermal water loss is 10 times higher for an infant born at 24 weeks of gestation than for a term neonate.2Barrier function rapidly improves during the first 2 weeks after birth, but infants born at 25 weeks or less can have increased transepidermal water loss for significantly longer than 4 weeks after gestation.3 Benign clinical interventions such as barrier creams or ointments can dramatically decrease these losses. During this period, cutaneous contact with chemicals that can cause neurotoxicity, such as hexachlorophene, or alter thyroid function, such as povi-done iodine, should be avoided.2,4 Desiccated skin is even more susceptible to injury, providing a portal of entry for invading microbes and increasing the risk of disseminated infection.
DEVELOPMENTAL DEFECTS AND SELECTED BIRTHMARKS
APLASIA CUTIS CONGENITA
The congenital absence of skin is a cutaneous anomaly most often seen at the scalp vertex. Sharply marginated lesions may present either singly or as multiple ulcers, bullae, or scars that measure up to several centimeters in diameter (eFig. 357.1 ). Aplasia cutis can have underlying skull defects, and larger irregular defects may extend to the dura or meninges. These larger lesions are more often familial and may be complicated by meningitis, hemorrhage (which can be fatal), or sagittal sinus thrombosis.5 Aplasia cutis of the trunk and extremities is often strikingly symmetric in distribution. Histologically, aplasia cutis is characterized by absent epidermis, diminished dermis and adnexal structures, or, in full-thickness lesions, the absence of all skin layers.
Several distinct subtypes of aplasia cutis have been described on the basis of distribution, mode of inheritance, and associated abnormalities. Most aplasia cutis congenita occurs sporadically, but autosomal dominant and autosomal recessive transmission have also been well documented. Associated abnormalities include cleft lip and palate, limb anomalies, cutaneous organoid nevi, and epidermolysis bullosa. Aplasia cutis may mark underlying cranial defects, spinal dysraphism, omphalocele, or gastroschisis.
The cause of aplasia cutis congenita is unknown, but incomplete closure of the neural tube or embryonic fusion lines has been proposed as a possible etiology.6 The findings of a twin fetus papyraceous and/or a placental infarct have suggested vascular thrombosis as a cause in infants with lesions on the trunk and limbs.
Cutaneous and bony lesions usually heal spontaneously over a period of weeks to months. A hypertrophic or atrophic patch of alopecia remains. Lesions that fail to heal or produce cosmetically unacceptable scars can be excised with primary closure after appropriate imaging is done to rule out underlying defects.
MIDLINE LESIONS
Midline circumscribed or annular hypertrichosis, dimples, sinuses, skin tags, nodules, and cysts may be isolated skin findings or may mark underlying developmental defects. The differential diagnosis of lesions on the brow or nose includes dermoid cyst or sinus, glioma, and encephalocele. Congenital defects that present as a midline scalp nodule include encephalocele, meningocele, aplasia cutis, dermoid cyst or sinus, and heterotopic brain tissue. If the diagnosis of a midline scalp lesion is clinically uncertain, skin biopsy should be postponed until after radiographic imaging by computed tomography or magnetic resonance imaging. These studies may miss small associated intracranial connections, however.
A midline pit or nodule on the neck may represent a cervical cleft or thyroglossal duct cyst or sinus. A remnant of respiratory epithelium known as a bronchogenic sinus or cyst presents at birth as a nodule or pit at the suprasternal notch. Branchial cleft anomalies, cysts or sinuses, are located along the preauricular area, pinna, and lateral neck. These sinuses and cysts can be watched expectantly or electively removed by surgical excision to prevent drainage or infection.
A variety of midline lumbosacral skin lesions, including pits, lipomas (often manifesting as a deviated gluteal cleft), skin tags or pseudotails, localized hypertrichosis, hemangiomas, and nevus flammeus, may mark occult spinal dysraphism (eFig. 357.2 ). Sacral dimples or sinuses are common lesions and are of more concern when they occur superior to the gluteal cleft or in combination with other cutaneous signs of dysraphism. Diffuse hypertrichosis and nevus flammeus are also commonly seen over the lumbar spine, and in isolation, they are less likely to be a sign of spinal dysraphism. In contrast, radiographic imaging is indicated for sacral hemangiomas, lipomas, or skin tags.
AMNIOTIC BANDS
Amniotic bands cause circumferential ringlike constrictions on the skin, most commonly on the extremities. They are present at the time of birth and appear to be caused by separation of the amnion from the chorion, giving rise to strands of amnion, which disrupt normal morphogenesis. Amniotic bands can cause a multitude of other abnormalities, including limb amputations, syndactyly, thoracoabdominal wall defects (eg, gastroschisis, omphalocele), and craniofacial clefts.
SUPERNUMERARY NIPPLES
Supernumerary nipples are reddish brown papules or dells that occur anywhere along the embryologic milk lines of the chest, abdomen, or, rarely, the inguinal area (eFig. 357.3 ). They may be accompanied by breast tissue and are sometimes mistaken for melanocytic nevi. Further evaluation and treatment is usually unnecessary. Supernumerary nipples may be electively removed by surgical excision.
ACCESSORY TRAGUS
Accessory tragi are pedunculated flesh-colored papules occurring anywhere from the preauricular area to the angle of the mouth (eFig. 357.4 ). They are present at birth and can be multiple or bilateral. They are usually localized lesions but can be associated with other branchial arch syndromes. Association with deafness and renal abnormalities is controversial, and screening is only recommended if there are other worrisome features present. They should be removed by an experienced surgeon because most lesions contain cartilage and may have connection with the external ear canal.
SUPERNUMERARY DIGITS
Most common on the fifth finger, supernumerary digits can range from subtle papules to full-sized digits. These lesions often contain cartilage and nerves; thus, they should not be ligated but instead removed by a surgeon with nerve dissection to avoid development of a traumatic neuroma.
MEDIAN RAPHE CYSTS
These white-colored papules along the ventral penis, scrotum, and perineum represent incomplete closure of the urethral and/or genital folds (eFig. 357.5 ). They are usually asymptomatic and resolve over time without treatment.
NEVUS SEBACEUS
Usually a localized lesion on the scalp or face, nevus sebaceus presents at birth as a hairless linear plaque of coalesced salmon- to yellow-colored papules (Fig. 357-1). A biopsy reveals absent to malformed hair follicles with an abundance of sebaceous glands. Because of the 10% to 30% risk of tumor formation, especially basal cell carcinoma, removal by adolescence is usually recommended.7
EPIDERMAL NEVUS
Epidermal nevi are composed of verrucous-appearing, tan to brown, linear coalescing papules, which can be present at birth but often develop later in childhood. The distribution and size is variable, but lesions are more commonly localized, and the neck, trunk, and extremities are common sites. Treatment is difficult because recurrence is common after destruction or excision.
COMMON BENIGN DERMATOSES
SEBACEOUS HYPERPLASIA
Numerous tiny, pale yellow papules representing hypertrophic sebaceous glands are seen on the nose, forehead, cheeks, and upper lip of full-term newborns. The condition resolves with waning maternal androgen levels during the first weeks of life.
FIGURE 357-1. Nevus sebaceus on the posterior scalp.
MILIA
Milia are tiny cysts walled by incompletely canalized follicular or ductal epithelium and filled with sloughed keratinocyte and sebaceous debris. Milia are most common on the face of full-term newborns but may be seen on other areas. Epstein pearls, yellow papules often found on the hard palate, are intraoral milia. Milia usually disappear within a few weeks.
NEONATAL ACNE
The small inflammatory papules and pustules of neonatal acne may be present at birth or develop within the first 2 to 3 weeks of life. Comedones are characteristically absent. The etiology is unclear, but current hypotheses suggest an association with Pityrosporum species versus the traditional theory of maternal and fetal androgen influence. Therefore, neonatal acne may not be a true form of acne, and “neonatal cephalic pustulosis” has been proposed as a replacement term. The condition is rarely severe enough to require treatment and usually resolves spontaneously within 2 to 3 months. Pustules caused by Pityrosporum (Malassezia furfur) contain characteristic spores and short hyphae; these resolve promptly with application of topical antifungal creams. Infantile acne typically develops at 2 to 3 months of age (or can be persistent neonatal acne) with inflammatory papules, pustules, and comedones. Persistent or severe acne in an infant is a sign of adrenal or androgen excess in the minority of cases. Normal growth velocity and bone age are usually sufficient to rule out extracutaneous disease in an otherwise healthy infant. Nodulocystic acne warrants dermatologic referral for more aggressive therapy.
NEONATAL VESICLES AND PUSTULES
Many conditions cause blisters and pustules in the newborn. Vesicles are defined as small intraepidermal or subepidermal pockets of clear fluid. If the lesions are large (> 1 cm), they are referred to as bullae. Pustules are filled with purulent fluid. Diseases in this category range from the totally innocuous and self-limited to the severe and life threatening. Often, initial empiric broad-spectrum systemic antimicrobial therapy is warranted, especially in unstable premature infants. A family history of blistering diseases and physical examination, including examination of the placenta, can focus the differential diagnosis. Bullae and widespread involvement should prompt a more aggressive workup. The differential diagnosis of infectious and noninfectious causes of blisters, pustules, and erosions in the newborn are summarized in Table 357-1. Infectious causes are discussed in Section 17 and genetic causes are discussed in detail in Chapter 360. The relatively more common noninfectious causes of vesicles and pustules in the neonate are discussed in more detail here.
SUCKING BLISTERS
Sucking blisters are common, transient lesions that result from intrauterine sucking. Typically, 1 or 2 blisters or erosions are present at birth on the radial forearm, wrist, or dorsal thumb or index finger. The diagnosis is usually confirmed by observing the infant sucking vigorously on the affected area.
MILIARIA
Also called prickly heat, this common skin finding results from incomplete canalization of the eccrine ostia with resultant accumulation of sweat droplets within the skin. Three clinical variants reflect the depth of obstruction. Miliaria crystallina are superficial, subcorneal vesicles (eFig. 357.7 ). Miliaria rubra occur within the epidermis, accompanied by focal rupture of the duct and an inflammatory response, producing erythematous papules and pustules. Miliaria profunda, uncommon in neonates, are deeper edematous papules occurring within the dermis. Miliaria is precipitated by excessive heat or bundling. Common sites include the forehead, torso, and arms. The condition is self-limited and relieved by placing the infant in a thermoneutral environment.
ERYTHEMA TOXICUM NEONATORUM AND TRANSIENT NEONATAL PUSTULAR MELANOSIS
Common, transient, and innocuous eruptions, erythema toxicum neonatorum and neonatal pustular melanosis may occur simultaneously and may share a common pathophysiology. The exact etiology is unknown, but a recent theory suggests erythema toxicum may be related to an inflammatory reaction to microbes penetrating into the skin through the hair follicle.8Erythema toxicum occurs in 50% to 70% of term newborns, equally in boys and girls, but is uncommon in premature infants.9 In most infants, the onset is in the first 2 days with resolution within 1 week. Three types of skin lesions may be present in varying proportions: erythematous macules, wheals, and vesiculopustules, usually arising from an erythematous base (eFig. 357.8 ). Lesions can occur almost anywhere on the body, but palmoplantar and perioral sparing are diagnostic features. Transient neonatal pustular melanosis occurs in 5% of term African American infants and in less than 1% of Caucasian infants.10 The eruption is always present at birth or within the first 24 hours. Lesions evolve from noninflammatory pustules that rupture, leaving transient collarettes of scale surrounding hyperpigmented macules that may persist for several weeks (Fig. 357-2). The pustular phase is evanescent and may occur in utero, leaving only pigmented macules at birth. The eruption may occur on any part of the skin but usually involves the face, neck folds, hands, and feet. The differential diagnosis of pustular eruptions is extensive and includes infectious processes that require immediate treatment (see Table 357-1). Skin biopsy is indicated if the diagnosis is uncertain.
ACROPUSTULOSIS OF INFANCY
This intensely pruritic eruption consists of vesicles and pustules localized mainly to the palms, soles, and lower extremities (eFig. 357.9 ). Lesions may be present at birth but usually develop in early infancy. It is more common in males and in African Americans. Lesions reoccur in crops every 2 to 3 weeks and fade over the next 7 to 10 days. The condition closely mimics scabies, but repeated skin scrapings are negative for evidence of mites, and empiric treatment for scabies is ineffective. Skin biopsy is not usually necessary but will reveal an intraepidermal vesicle containing eosinophils or neutrophils. Treatment with potent topical steroids or oral antihistamines may relieve symptoms. The use of ultrapotent (class I) topical steroids may be justified in severe cases.
EOSINOPHILIC PUSTULAR FOLLICULITIS
A variant of eosinophilic folliculitis occurs in infants and, rarely, neonates. It is characterized by pruritic, recurrent crops of pustules. Unlike acropustulosis of infancy, the lesions are most commonly seen on the scalp, although they can occur on the trunk and extremities as well. Skin biopsy reveals a perifollicular infiltrate of eosinophils. The etiology is unknown, but potent topical steroids and oral antihistamines seem to be helpful. The lesions eventually resolve over several months.
INCONTINENTIA PIGMENTI
Incontinentia pigmenti is an uncommon X-linked dominant blistering genodermatosis that occurs predominantly in females (see Chapter 360). Skin manifestations occur in 4 variable, overlapping stages: vesicular, verrucous, hyperpigmented, and hypopigmented atrophic lesions.13 Vesicular lesions are often present at or shortly after birth, usually lasting from 2 weeks to 4 months. The distribution of the vesicles is distinctively linear, following the lines of Blaschko, and can be focal or extensive (eFigs. 357.10 and 357.11 ).
ERYTHRODERMA
Generalized redness and scaling in infancy has an alarming appearance and is often clinically and histologically nonspecific. An infant’s general state of well-being and the family history provide important clues to the underlying cause. Definitive diagnosis may be possible only after a period of observation. The spectrum of disease includes common conditions limited to skin, infections, nutritional deficiencies, and immunologic disorders.
Infectious causes of erythroderma should always be considered first. The differential diagnosis includes systemic candidiasis, staphylococcal scalded skin syndrome, syphilis, and AIDS (see Section 17 ). Laboratory evaluation should include complete blood count; potassium hydroxide preparation (or Calcofluor White immunofluorescence); Tzanck smear; and surveillance cultures of the nasopharynx, rectum, umbilicus, conjunctivae, urine, and blood. Consider syphilis serology and HIV studies in epidemiologically relevant locales.
Erythroderma coupled with failure to thrive, diarrhea, and recurrent infections should prompt a search for metabolic or immunologic abnormalities with assessment of dietary history, electrolytes, protein, albumin, alkaline phosphatase, microscopic examination of hair, and a sweat test. Erythroderma in the neonate may be seen with primary immunodeficiencies (severe combined immunodeficiency, Wiskott-Aldrich, hyperimmunoglobulin E, Omenn syndrome), secondary immunodeficiencies (AIDS, graft-versus-host disease), Langerhans cell histiocytosis, neonatal lupus, and diffuse cutaneous mastocytosis. Erosive, periorificial dermatitis suggests a metabolic or nutritional disorder. Cystic fibrosis is the most common condition in this category. Other possibilities include acrodermatitis enteropathica, biotin-dependent multiple carboxylase deficiency, prolidase deficiency, methylmalonic acidemia, maple syrup urine disease, propionic acidemia, citrullinemia, Gaucher disease, and kwashiorkor. More directed laboratory evaluation includes blood smear for leukocyte vacuoles, HIV screen, plasma zinc, and serum linoleic and arachidonic acids; amino acid and organic acid profiles; biotinidase activity; antinuclear antibody, SS-A, and SS-B titers; quantitative immunoglobulins and tests of cell-mediated immunity; skeletal survey; hair examination; and skin biopsy.
Table 357-1. Differential Diagnosis of Blisters and Pustules in the Newborn
FIGURE 357-2. Neonatal pustular melanosis. Note superficial pustules and hyperpigmented macules, surrounded by a collarette of scale that appears within the first 24 hours of life.
Primary cutaneous conditions should be considered in thriving infants (see Chapter 358). The diagnosis may not be clear until after the neonatal period. Helpful clues to the diagnosis of atopic dermatitis are involvement of the face and extensor extremities with marked sparing of the diaper area. Seborrheic dermatitis and psoriasis frequently involve the diaper area and skin folds. The skin lesions of infantile psoriasis are often sharply circumscribed, but scale may not be prominent. In addition, disorders of ichthyosis often present with congenital erythroderma (see Chapter 360).
Table 357-2. Conditions Associated with Neonatal Purpuric Nodules
PETECHIAE AND PURPURA
Conditions associated with nonblanching purpuric nodules are listed in Table 357-2. Skin lesions of the classic “blueberry muffin” phenotype represent extramedullary hematopoiesis and occur as a result of congenital infection with syphilis, rubella, cytomegalovirus, coxsackievirus, or toxoplasmosis; severe intrauterine anemia from Rh or ABO incompatibility; or twin transfusion syndrome. Skin biopsy revealing nucleated red blood cells and usually other erythroid and sometimes myeloid precursors distinguish these lesions from the purpuric nodules associated with neoplastic infiltrates from congenital leukemia, neuroblastoma, myofibroma, or vascular tumors (eFig. 357.12 ). Infectious or inflammatory vasculitis can also present with clinically similar but histologically distinct skin lesions. When the cause of such skin lesions is not obvious, evaluation should include the following: complete blood count with differential, reticulocyte counts, and blood smear examination; liver function tests; cord blood for IgM concentration; maternal and cord blood for congenital infections, including syphilis; viral cultures of the nasopharynx, rectum, and urine; and biopsy of 1 or more skin lesions.