Chapter 7

Dermatology

Newborn skin is thinner, it is less hairy, it has less pigment, it has a weaker attachment of the epidermis to the dermis, and newborns may have brown fat. ^∗

The skin of premature infants is immature and has compromised barrier function ( Fig. 7-1). Clinical consequences include increased transepidermal water loss; fluid and electrolyte disturbances; temperature instability; infection (cutaneous and systemic); absorption of substances applied to the skin; and susceptibility to mechanical, chemical, and thermal stresses.

Most premature infants exhibit rapid maturation of skin barrier function over the first 2 to 3 weeks of life. In infants born before 25 weeks’ gestation, skin barrier function may require 8 weeks or longer after birth to mature.

Prilocaine, resorcinol, aniline dyes, and methylene blue can lead to methemoglobinemia. ^∗

Hypothyroxinemia and goiter have been reported. ^∗

Skin injury may accompany routine care of very premature infants. Anetoderma of prematurity is the term for focal depressions or outpouchings, which are presumed to be a response to mechanical or thermal injury to the skin.

Although bacteria, especially Staphylococcus and Streptococcus species, should always be considered as a cause of cutaneous pustules, tape sites have been associated with opportunistic fungal infections of the skin, especially involving Aspergillus species. Other fungi and yeast, including Rhizopus and Candida organisms, should also be considered. Performing a biopsy and culture is a standard approach to diagnosis. ^∗

Infants that receive numerous heel sticks may develop calcinosis cutis over the heel. This seldom shows up until several months after discharge. The presenting symptoms are small yellow or white papules that can be mistaken for warts. They are generally not symptomatic and will often resolve by 30 months of age. If they become problematic, they can be treated with curettage.

Subcutaneous fat necrosis of the newborn usually appears within the first weeks of life with red to violaceous mobile plaques, especially on the back, thighs, and cheeks. The cause of subcutaneous fat necrosis is not definitively known.

Subcutaneous fat necrosis may occur in cases of fetal distress, birth trauma, infection, or cold stress. It is increasingly being seen after the use of whole body cooling for the treatment of hypoxic-ischemic birth injury. ^∗

Although the disorder is most often benign and self-limited, in some cases subcutaneous fat necrosis of the newborn may be associated with hypercalcemia and death. Therefore serum calcium levels must be monitored, and caregivers must be vigilant for clinical signs and symptoms of hypercalcemia.

Findings of sclerema usually appear in the first 2 weeks of life but can begin as late as 4 months. Infants who are poorly nourished, dehydrated, hypothermic, or septic are most commonly affected. Sclerema neonatorum begins in the lower extremities with the appearance of hard, cool skin and decreased mobility and subsequently ascends to involve the trunk and face. Palms, soles, and genitalia are usually not involved. Joints become immobile, and the face appears masklike. Sclerema may be associated with necrotizing enterocolitis, pneumonia, intracranial hemorrhage, hypoglycemia, and electrolyte disturbances. ^∗

Sclerema is likely a result of lipoenzyme dysfunction and occurs in infants who are stressed with severe illnesses. More specifically, dysfunction of enzymes regulating the conversion of saturated fatty acids to unsaturated fatty acids results in an excess of saturated fatty acids. This dysfunction promotes fat solidification. The incidence of sclerema has decreased significantly in recent years because events such as malnutrition, dehydration, and hypothermia occur less commonly in modern nurseries. Treating the underlying condition can result in resolution of sclerema. Some authors also propose systemic steroids or therapy with exchange transfusions.

Cutis marmorata is a reticulated (i.e., netlike) mottling of the skin seen in most infants. It is seen most often when the environment is cooler and will usually improve if the infant is warmed. It usually improves in childhood, but can be persistent in patients with Down syndrome, trisomy 18, and Cornelia de Lange syndrome.

Harlequin color change is a demarcated erythema forming on the dependent half of the body of newborns. In some cases the baby appears as if a line were drawn right down the midline. The more superior half of the body appears pale. This appearance can occur in any position and commonly lasts from seconds up to 20 minutes. It is rarely seen after 10 days of life. Harlequin color change is explained by immature autonomic vasomotor control because it is more common in premature infants and is reversible. If the baby is flipped over during an episode, the newly dependent portion will become erythematous.

All three forms represent cystic retention of keratin, appear and resolve in the first month, and can be present at birth. They are white, 1- to 2-mm papules that can be found singularly or in clusters.

Aplasia cutis congenita results from failure of the development of the normal layers of skin. It occurs most often on the scalp and may present clinically as an ulcer, healed erosion, or well-formed scar. Therefore it is often mistaken for trauma caused by a scalp pH probe. In cases of large lesions or lesions overlying the midline neurocranial axis, imaging should be considered because aplasia cutis congenita may be associated with underlying malformations of bone or may extend deeply to the meninges. Large and irregular lesions can also be associated with Adams–Oliver syndrome and chromosomal abnormalities.

Dermoid cysts form along embryonic fusion lines. They are congenital but may not be seen until childhood, when they begin to enlarge. They commonly occur along the orbital ridge. Surgical removal is recommended because they can become infected. When they are located along the lateral eyebrow, they do not require specific imaging. Other locations, especially midline, can have a connection to the central nervous system and should be imaged before surgery.

This description fits a dermoid sinus. Midline lesions should always raise the possibility of a developmental defect. The presence of a hair coming out of the sinus is especially significant because it is considered a marker for a connection with the central nervous system. The baby should be imaged before the defect is repaired.

Preauricular skin tags, also called accessory tragi, are embryonic remnants of the first branchial arch ( Fig. 7-3). The formation of the first branchial arch occurs during the fourth week of fetal development. Because this may be associated with hearing abnormalities, patients should have their hearing screened before they are discharged from the hospital. The evidence for associated renal problems in patients with no other associated abnormalities is controversial. Renal ultrasound should be considered for patients with additional dysmorphic features or a family history of deafness or renal malformations. ^∗

Accessory nipples, also called supernumerary nipples ( Fig. 7-4), are embryonic remnants of the mammary line that extend from the axilla to the inner thigh. They appear as pink or brown papules, with or without surrounding areola, anywhere along the mammary line. There have been conflicting reports about an association with urinary tract abnormalities. Current studies, however, have not found an association in patients who have no other anomalies.

A CMN is usually defined as a melanocytic lesion that is present at birth. The incidence is reported to be 0.5% to 2%.

Most CMNs do not have any associated complications. CMNs are often subdivided according to their size. A common classification is that a CMN greater than 20 cm in adulthood is considered to be large. Melanoma has been reported to arise within congenital lesions, but the exact risk for this complication is unclear. It is known that large lesions carry the greatest risk and that melanoma, when it occurs, does so earlier in life. Leptomeningeal melanosis is a rare complication that may occur in association with a giant congenital nevus with numerous satellite nevi. ^∗

The cause and nomenclature of these conditions remain somewhat controversial. Some neonatal outbreaks, although commonly called neonatal acne, are not composed of distinct pimples (i.e., comedones) but rather superficial pustules.

Erythema toxicum is a benign condition ( Fig. 7-5). Erythema toxicum is no alien to the nursery; it is present in 50% of term newborns. It is much less prevalent in premature infants, however, occurring in only approximately 5%.

Erythema toxicum usually begins between 24 and 48 hours of life and spontaneously resolves in 4 to 5 days; however, new lesions can occur up to day 10 of life. Exacerbations and remissions may occur in the first 2 weeks of life. Erythema toxicum lesions are irregularly bordered, erythematous macules, 2 to 3 cm in diameter, with central yellowish vesicopustules. They are mostly discrete, but some erythematous macules become confluent. Lesions do not involve the palms or soles.

Wright-Giemsa stains of pustule scrapings show mostly eosinophils. Up to 15% of affected infants demonstrate peripheral eosinophilia as well.

“Nothing works.” In other words, it is not necessary to do anything other than reassure the family that the condition will resolve over time ( Table 7-1).

Miliaria is found in up to 15% of neonates. Both forms are caused by eccrine duct obstruction and resultant sweat leakage to different levels of skin (crystallina if the leakage occurs under the stratum corneum; rubra if it takes place at the upper dermis). Miliaria is more common in hot, humid environments and is distributed to the forehead, upper trunk, and other covered surfaces. The best method of treatment is to try to keep the baby from becoming overheated. Removing excessive layers or putting the baby in an air-conditioned room may also be helpful. Topical ointments may aggravate the condition and are therefore not recommended.

Although atopic dermatitis classically includes pruritus, infants (especially newborns) may not have the coordination to scratch. However, occipital alopecia can result from excessive rubbing of the back of the head against the bedsheets. In this situation hair may fall out or break off as a result of friction.

If dermatitis involves the axillae or groin, it is more likely to be seborrheic dermatitis. If extensor surfaces such as forearms and shins are involved, atopic dermatitis is more likely. Both atopic dermatitis and seborrheic dermatitis involve scalp and posterior auricular areas, although seborrheic dermatitis has large, yellowish scale and, when severe, characteristically extends down to the forehead and eyebrow areas ( Table 7-2).

Intertrigo literally means an erythematous rash on opposing skin surfaces or skin folds. The common causes of intertrigo include seborrheic dermatitis or infections (e.g., Candida spp.) Other infections include Staphylococcus aureus or Streptococcal infections. Psoriasis, nutritional deficiency, and histiocytosis may also present as intertrigo. Clues to the diagnosis of histiocytosis include the presence of petechial or red-brown macules and papules, which are recalcitrant to topical therapy and occasionally associated with an enlarged lymph node or nodes.

Staphylococcal scalded skin syndrome (SSSS) is caused by toxins released by S. aureus that lead to blistering and desquamation of the skin. The Nikolsky sign is positive; simply rubbing the skin causes denudation of skin or formation of a blister. Clustered outbreaks of SSSS have been reported in newborn nurseries. Remember, however, that scalding thermal burns caused by bathing the newborn in overly hot water are also possible.

This term is used to describe neonates whose skin resembles a blueberry muffin (i.e., the skin shows diffuse, dark blue to violaceous purpuric macules and papules). The spots represent dermal hematopoiesis and are a sign of serious systemic disease, most often congenital infection. The congenital infection most commonly associated with this appearance is congenital rubella, although the condition may be caused by other microorganisms and diseases as well.

Infantile hemangiomas are common vascular tumors that arise during the neonatal period. They are often not visible at birth but are noticed within the first weeks of life. One study found that 10% of Caucasian children had hemangiomas when examined at 1 year of age. Hemangiomas occur more frequently in female children, with a female-to-male incidence of 2 to 5:1. In addition, they arise more commonly in premature infants, low-birth-weight infants, and infants born to older mothers and those with placenta previa and preeclampsia.

In older medical books and the lay literature, superficial hemangiomas were called strawberry birthmarks because the color and texture of affected skin is somewhat reminiscent of a strawberry. Deep hemangiomas have been called cavernous hemangiomas, but the term is particularly confusing because it has also been used to describe venous malformations, which are a completely different kind of vascular birthmark. Therefore it is prudent to avoid both terms and to use instead the terms superficial, deep, or mixed hemangiomas to describe the particular type of hemangioma.

This is one “clock” that does not get corrected for gestational age. Although hemangiomas are more common in preterm infants, and the female-to-male ratio is less pronounced, the chronologic age at which hemangiomas are noted to begin proliferation is the same as for full-term infants. ^∗

The classification of vascular birthmarks has historically been problematic. The most commonly accepted classification was introduced by the International Society for the Study of Vascular Anomalies in the 1990s. It divides vascular birthmarks into two broad categories:

Infants who present with more than five cutaneous hemangiomas are more likely to have underlying internal hemangiomas. The liver and gastrointestinal tract are the most common sites of extracutaneous involvement. It is important to remember that normal liver sonogram results in the neonatal period do not rule out subsequent hepatic hemangiomatosis because symptoms may develop during the proliferative phase of the hemangioma.

Not all children with multiple skin hemangiomas have underlying systemic involvement; conversely, children with visceral hemangiomas may have no skin lesions. Children with hemangiomas located on the lower face in a “beard” pattern may have laryngeal hemangiomas that may not become detectable until they compromise breathing. Therefore a pediatric otolaryngologist should evaluate these children early in life, and early treatment is often required. ^∗

Even smaller lesions in problematic locations can lead to complications. Hemangiomas located around the eye may obstruct the visual axis or lead to astigmatism by deforming the shape of the globe, which leads to visual impairment. Lesions on the tip of the nose can cause deformation of the cartilage and permanent disfigurement. Large lesions with high flow may cause congestive heart failure. Ulceration may complicate large or small hemangiomas. Ulceration is most common in the diaper area and in high-friction areas.

Segmental hemangiomas are flatter hemangiomas that seem to involve a whole facial segment (>5 cm) or a large area on the pelvis. They are often markers of other developemental abnormalities. Large facial hemangiomas are associated with PHACE syndrome (Posterior fossa malformation, Hemangioma, Arterial abnormalities, Cardiac abnormalities, Eye abnormalities). Segmental hemangiomas that involve the sacrum and perineum can be associated with genitourinary anomalies and tethered spinal cord. ^∗

Thyroid function testing should be considered. Hemangioma tissue may exhibit enzyme activity (type 3 iodothyronine deiodinase), which inactivates thyroid hormone. Laboratory testing should be performed even if the newborn screen results were within normal limits because enzyme activity can increase during the proliferative phase of the hemangioma. ^∗

RICH is an acronym for a rapidly involuting congenital hemangioma.

Hemangiomas of infancy can have precursor lesions present at birth but usually do not begin to proliferate until after 2 weeks of age. They proliferate for several months and slowly involute over years. Congenital hemangiomas are present more fully formed at birth. They undergo rapid involution, usually within 1 or 2 years, and are thus named rapidly involuting congenital hemangiomas. There is also a subtype of congenital hemangiomas that do not involute and are therefore named noninvoluting congenital hemangiomas (NICHs).

Neuroblastoma, rhabdomyosarcoma, fibrosarcoma, primitive neuroectodermal tumor, liposarcoma, and lipoblastoma are among the lesions that may mimic the appearance of a hemangioma.

Although smaller hemangiomas that are not problematic do not require treatment, other types do require treatment to prevent problems. Problematic hemangiomas include those that compromise vital functions, cause significant distortion or disfigurement of normal underlying structures, and have ulcerated or become infected. Treatment strategy varies depending on the clinical situation. The recent use of propranolol to treat hemangiomas has led to significant improvement in care. However, this is a relatively new indication for this medication, and considerations with its use are appropriate. ^∗

Propranolol is a nonselective beta blocker. Side effects include hypotension, bradycardia, hypoglycemia (especially when fasting), bronchospasm, and sleep disturbance. Underlying heart disease or arrhythmias should be ruled out before starting off-label use of this medication to treat infantile hemangiomas.

Hemangiomas in this location may be associated with underlying spinal cord anomalies (e.g., a tethered spinal cord), underlying bony defects, and anomalies of the genitourinary and gastrointestinal systems. For detection of a tethered cord, magnetic resonance imaging is the study of choice. (See the following Key Points box for additional cutaneous clues to underlying spinal cord abnormalities and Fig. 7-7 for a striking example of multiple congenital anomalies overlying the midline lumbrosacral spine).

Kasabach–Merritt phenomenon (or syndrome) is a rare complication that occurs in infants with large vascular tumors. Patients usually exhibit symptoms in the first few months of life with a rapidly enlarging vascular mass associated with profound thrombocytopenia and coagulopathy. It is a life-threatening condition. In the past this phenomenon was thought to be a complication of garden-variety hemangiomas, but recent evidence indicates an association with rare vascular tumors such as kaposiform hemangioendothelioma and tufted angioma. ^∗

A lymphangioma, also known as a lymphatic malformation, is a vascular malformation composed of lymphatic tissue. These lesions are sometimes noted in the immediate newborn period or may become more prominent as a child grows. They do not regress spontaneously. A cystic hygroma is one type of lymphatic malformation that is composed of larger cystic spaces, also called a macrocystic lymphatic malformation. It usually is apparent in the immediate newborn period and is located on the head and neck. Some patients with cystic hygroma have underlying genetic abnormalities such as Turner syndrome.

A port-wine stain is a malformation composed of small capillary and venular-size vessels. As a child matures, the lesion may darken, thicken, and develop blebs. Pulsed dye laser therapy is the preferred method of treatment and may lead to significant lightening in many patients. Multiple treatments are usually required. These lesions differ from the “stork bite” and “angel kiss” nevus simplex, which do not progress and do not need to be treated. ^∗

Approximately 10% of children with a port-wine stain in the distribution of the ophthalmic branch of the trigeminal nerve have findings of Sturge–Weber syndrome. Sturge–Weber syndrome is characterized by seizures (onset usually occurs in patients younger than 2 years old), hemiplegia, mental retardation, and glaucoma. In infancy, however, many of these findings may not be present or may be difficult to discern. Similarly, a computed tomography or magnetic resonance imaging scan in infancy may not show the characteristic calcification, cerebral atrophy, or abnormalities of the cortex and white matter. An enlarged choroid plexus or increased myelination, though, may be present early in the course of Sturge–Weber syndrome. Neonates with a port-wine stain in that distribution should have an urgent eye examination to assess for possible glaucoma.

Both diseases are autosomal dominant, but spontaneous mutations account for approximately half of cases. The incidence of neurofibromatosis type 1 is 1 in 2500; the mutated gene product is neurofibromin, a protein involved in tumor suppression. Neurofibromatosis type 2 has a reported incidence of 1 in 33,000; the involved gene product is merlin, which mediates cytoskeleton and extracellular movement. ^∗

Neurofibromatosis type 1 should be suspected in any infant with multiple café-au-lait spots, congenital glaucoma, a plexiform neurofibroma, or pseudoarthrosis. Without a positive family history, however, it can be difficult to diagnose neurofibromatosis in the first months of life. The diagnosis requires two or more of the following criteria: at least six café-au-lait macules of at least 0.5 cm before puberty (1.5 cm postpuberty), at least two neurofibromas, one plexiform neurofibroma, axillary freckles or inguinal freckles, at least two Lisch nodules (iris hamartomas), osseous lesions, or a first-degree relative with neurofibromatosis type 1. Other features that are associated with neurofibromatosis in older children include learning disability, macrocephaly, short stature, scoliosis, juvenile xanthogranulomas, angiomas, mental retardation, impaired coordination, seizures, cerebral tumors (i.e., optic gliomas), increased risk of malignancy, and hypertension.

Hypopigmented macules, known as ash leaf spots, are the most common skin findings of tuberous sclerosis in infants. Connective tissue nevi, known as shagreen patches, may also be present at birth. Adenoma sebaceum (facial angiofibromas) generally appear at 3 years of age and older; periungual or gum fibromas appear in early adulthood. During the first months of life hypopigmented macules may be recognizable only with a Wood’s lamp because of the general lack of pigmentation in the skin. Another manifestation of tuberous sclerosis during the neonatal period that is of concern is a rhabdomyoma within the heart. Infants diagnosed with tuberous sclerosis should have a cardiac echocardiography examination performed. Cardiac lesions that are asymptomatic often regress by the first year of life.

Absolutely not. Most hypopigmented macules are a variant of normal conditions. However, multiple ash leaf–like macules, a family history of tuberous sclerosis, neonatal seizures, cardiac rhabdomyomas, or renal cysts should alert the clinician to the possible diagnosis of tuberous sclerosis.

Two distinct chromosomal complexes on two different chromosomes are implicated as areas of mutation that result in tuberous sclerosis. Tuberous sclerosis complex 1 results from mutations in the gene hamartin on chromosome 9, located at 9q34.3. Tuberous sclerosis complex 2 is caused by mutations in the tuberin gene on chromosome 16 at 16p13.3.

Collodion baby is a term used to describe a neonate born with a yellow, shiny membrane that resembles collodion. It is often associated with ichthyosis. The word ichthyosis comes from the greek word ichthys, meaning “fish.” Patients with these conditions can have thickened, scaly or flaky skin.

Of newborns with collodion membrane, the most common ichthyosis that develops is nonbullous ichthyosiform erythroderma, also called congenital ichthyosiform erythroderma. Lamellar ichthyosis is another rare form of ichthyosis that may present initially with collodion membrane. Both are classified as autosomal recessive congenital ichthyoses. Approximately 5% of babies with collodion membrane do not go on to have clinically significant skin disease. Furthermore, not all patients with ichthyotic skin disease have a collodion membrane at birth. ^∗

Starting from the top, a microscopic examination of the hair can be performed, because patients with the rare condition trichothiodystrophy will have a distinctive “tiger tail” appearance under polarized light. An ophthalmology examination may show signs of “glistening dots,” which is pathognomonic for Sjögren–Larsson syndrome. A peripheral blood smear is useful to evaluate for lipid inclusions within white blood cells, which may be present in neutral lipid storage disease (Chanarin–Dorfman syndrome). In neonates with an ichthyosis syndrome a skin biopsy may not be helpful in the neonatal period because the cutaneous phenotype takes time to develop.

Supportive care is important until the collodion membrane sheds. Affected newborns experience difficulty with temperature regulation, are prone to sepsis, and have increased fluid and nutritional requirements. Therefore temperature should be controlled in an incubator, and any signs of infection should be promptly investigated and treated. Ectropion occurs as a result of taut skin everting eyelid margins, which leaves patients at risk for corneal ulceration. Topical ocular lubricants should be instituted early. Eclabium occurs by a similar mechanism of taut skin everting the lips. Nasogastric tube feedings may be required for poor suck and feeding difficulties.

The term harlequin baby is used to describe neonates born with massive shiny plates of stratum corneum with deep, red fissures that form geometric patterns resembling a harlequin costume. This entity is quite different from a harlequin color change, which is benign. As in neonates with collodion membrane, temperature regulation is defective, fluid requirements are increased, and risk of infection is high. The skin defect is usually restrictive, and respiratory insufficiency results. Harlequin babies rarely survive beyond the neonatal period.

The X-linked ichthyosis steroid sulfatase deficiency is associated with failure to progress during labor. Mothers have difficulty with cervical dilation and fail to adequately respond to intravenous oxytocin often necessitating a forceps delivery or cesearean section.

KID syndrome is a rare disorder characterized by keratitis, ichthyosis, and congenital neurosensory deafness. Newborns have erythematous, thickened skin that eventually peels. The face and extremities then become ichthyotic; scaly keratoconjunctivitis usually develops during infancy.

Epidermolytic hyperkeratosis is also called bullous congenital ichthyosiform erythroderma, and under the updated classification it is called epidermolytic ichthyosis. Newborns most often demonstrate blisters or bullae along with denuded skin. Although subtle hyperkeratosis appears in some newborns, it usually develops over time as the blistering subsides.

Epidermolysis bullosa is a heterogeneous group of inherited disorders characterized by skin fragility and blistering ( Fig. 7-8). Most patients develop symptoms in the newborn period. The most common types are epidermolysis bullosa simplex, junctional epidermolysis bullosa, and dystrophic epidermolysis bullosa. Within each subset there are different clinical phenotypes. It is now understood that these diseases are caused by an inability to synthesize proteins that play an important role in maintaining the skin’s integrity. Epidermolysis bullosa simplex is caused by mutations in keratins located in the basal layer of the epidermis; junctional epidermolysis bullosa is caused by defects in the protein laminin 5 and other proteins at the dermal–epidermal junction, and dystrophic epidermolysis bullosa is caused by a defect in collagen VII. There is no cure for these conditions, and treatment is supportive, although trials of bone marrow transplant and gene transfer are ongoing.^∗

Skin trauma (e.g., rubbing, chafing) is strongly discouraged, because the skin will likely blister or erode at the site. Tape should not be applied directly to the skin. New blisters should be ruptured with a sterile needle or lancet (to prevent them from enlarging), with the blister roof left in place, and dressed with a topical antibiotic and nonadherent dressing (e.g., plain petrolatum and gauze). The blisters should be monitored closely because superinfection may be a complication. Infants with severe forms of epidermolysis bullosa are at risk for nutritional deficiencies, poor weight gain, and anemia.