Congenital Cutaneous Lesions and Infantile Rashes

Pink (Vascular or Other)

Vascular birthmarks can be classified into two groups: tumors and malformations ( Table 60.3 ). Infantile hemangiomas are the most common of the vascular tumors, and their behavior is characterized by a growth phase (endothelial proliferation), followed by a plateau or stabilization phase and then an involutional phase. Vascular malformations are usually apparent at birth and tend to be relatively stable developmental abnormalities of vessels, including any combination of capillaries, veins, arteries, and lymphatic vessels ( Table 60.4 ).

Infantile hemangiomas are the most common benign tumors occurring in children. These lesions develop in approximately 4% of White infants by 1 year of age. Females are affected approximately 3 times as often as males. The incidence is higher in premature infants. Other risk factors for hemangiomas include low birthweight and multiple gestations. The natural course of infantile hemangiomas includes proliferative and involutional phases that end in complete, spontaneous regression in most cases. There is some thought that infantile hemangiomas may be triggered by hypoxia, either through maternal events or the infant factors.

There are three types of infantile hemangiomas:

• 1.

  Superficial hemangiomas, once referred to as strawberry marks, are the most common type (60%). They are bright red with well-demarcated borders ( Fig. 60.10 ). Often, a pale pink stain or bruiselike patch is noted at birth before taking its more characteristic form.

  

• 2.

  Deep hemangiomas, previously known as cavernous hemangiomas, are the least common of the three types (15%). They typically have a blue-violaceous to skin-colored surface. These lesions involve the deep reticular dermis and subcutaneous tissue. These may not be noted until the infant is a few months old.

• 3.

  Mixed hemangiomas (25%) possess both superficial and deep components ( Fig. 60.11 ).

  

Most infantile hemangiomas occur on the head and neck, but any area of the body may be involved. Infantile hemangiomas may be indistinguishable from port-wine stains in the early weeks of life. Lesions must be followed closely during the first few weeks after birth to determine whether a proliferative phase is present. Although the cause of infantile hemangiomas is not clear, their natural course has been well documented. The initial lesion may be a white macule with central threadlike telangiectases or a red macule resembling a port-wine stain. A peripheral zone of pallor representing vasoconstriction may be noted at this stage. Within the first few months of life, the macule becomes raised and enlarges. During the first 6 months of life, infantile hemangiomas proliferate at a rapid rate, and after 6 months, the lesions grow at a slower rate. Deep hemangiomas (and to a lesser extent mixed hemangiomas) have a slightly delayed onset of growth but also have sustained growth when compared to superficial hemangiomas. Involution may begin as early as the first year of life and is heralded by a color change from bright cherry red to dull red violet. Deep hemangiomas start to lose their blue-violet hue. In time, the central portion of the superficial hemangioma develops a grayish-white color that eventually extends to the periphery of the lesion. Lesions on the lips and nose and deep hemangiomas usually involute more slowly. It is not possible to predict precisely how long an infantile hemangioma will take to involute. Statistically, 50% of lesions are gone by 5 years of age, 70% by 7 years, and more than 90% by 9 years. Once resolved, residual skin changes such as hypopigmentation, atrophy, and telangiectases may be present in up to 10–20% of affected patients. If infantile hemangiomas have grown rapidly during their proliferative phase or were very exophytic, residual fibrofatty tissue may also be seen.

Infantile hemangiomas have many potential complications and associations ( Table 60.5 ). For most, no treatment is needed. Management of infantile hemangiomas is based on a variety of factors. These include the size of the lesion, location of the lesion, age of the patient, rate of growth/involution at the time of presentation, and risk or presence of complications. β Blockers, such as oral propranolol or topical timolol 0.5% solution, are the initial treatment of choice. The most common adverse events are sleep changes and cool extremities, but more serious concerns are hypotension, bradycardia, and hypoglycemia, though these are rare. A pretreatment screening should include clinical examination to identify patients who are at risk for cardiac or pulmonary abnormalities.

Lesions that may need to be treated include those on the midface, labial, periorbital, genital, or diaper area. These lesions warrant close clinical observation during the rapid growth phase of early infancy. Additional therapeutic modalities that are more rarely used include intralesional steroids, pulsed dye laser therapy, surgery, embolization, and sclerosing agents.

Location of infantile hemangiomas (segmental on face or beard distribution) as well as on the spine and lower back should raise concern for PHACE syndrome or PELVIS/SACRAL syndrome, respectively.

Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and eye abnormalities (PHACE) syndrome is a rare syndrome that affects a subgroup of infants with infantile hemangiomas. It is likely the most common vascular neurocutaneous disorder. The cutaneous findings tend to be larger hemangiomas (>5 cm) and also tend to be segmental, rather than arising from one point. These hemangiomas can be more confluent, have a telangiectatic appearance, or be composed of grouped papules. They are nearly always located on the head or face. It is important to distinguish them from capillary malformations. Approximately 20% of all infants with segmental facial hemangiomas have extracutaneous anomalies.

Criteria for PHACE syndrome include one segmental hemangioma of the head (>5 cm in diameter) plus one major criterion or two minor criteria. Major and minor criteria involve a group of cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline defects.

Cerebral vascular anomalies are the most common extracutaneous manifestation. The changes tend to be arterial, unlike Sturge-Weber syndrome, which involves capillaries. Imaging (MRI/magnetic resonance angiography [MRA] of the head and neck) greatly aids in the work-up of a patient with a segmental hemangioma on the face/head, looking for arterial changes, as a subset of patients are at increased risk for vasculopathy and ischemic stroke, though this remains a poorly understood complication.

Many congenital brain abnormalities have been noted in patients with PHACE syndrome: The most common ones are malformations of the posterior fossa and cerebellum. Most patients with congenital lesions will have normal neurologic examinations during infancy, and, thus, screening should not be based on abnormalities with the neurologic examination.

Cardiovascular anomalies may be seen on echocardiogram in up to 40% of patients and include coarctation of the aorta (most common), aberrant subclavian aneurysm, ventricular septal defect, and arterial aneurysms. Ocular abnormalities are somewhat rare in PHACE syndrome but include microphthalmia, optic nerve hypoplasia, persistent fetal vasculature, and morning glory disk anomalies. Midline defects including sternal cleft, supraumbilical abdominal raphe, and subtle changes such as sternal pits, dimples, or papules can be seen. A screening echocardiogram should be done for children who are at risk for PHACE syndrome.

Treatment typically is propranolol, and for patients with life-threatening hemangiomas, it can be initiated prior to obtaining imaging results. Propranolol is typically well tolerated in patients with PHACE syndrome, though it is recommended that they undergo a physical exam and echocardiogram prior to initiation, to make sure there is not coarctation of the aortic arch.

PELVIS, LUMBAR, and SACRAL syndromes are all different acronyms to describe disorders that include a segmental hemangioma of the perineal area or midline lower back with underlying abnormalities. The acronyms PELVIS (perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag) and SACRAL (spinal dysraphism, anogenital anomalies, cutaneous anomalies, renal and urologic anomalies, associated with angioma of lumbosacral localization) have been used to describe associations with occult spinal dysraphism. The risk of a spinal anomaly is ∼35% with a solitary lumbosacral hemangioma. MRI is more sensitive than ultrasound in evaluating for underlying spinal abnormalities in lumbosacral lesions, such as tethered cord.

Capillary malformations (also known as port-wine stains or nevus flammeus) occur in 0.3% of all newborns. They are present at birth and represent progressive ectasia of the superficial vascular plexus. These lesions do not undergo spontaneous resolution. They are usually unilateral and segmental but can be bilateral ( Fig. 60.12 ). The face and neck are the most commonly affected sites. Capillary malformations are typically pink to red during infancy and darken to reddish-purple hues with advancing age. Affected adults frequently have thickened, nodular port-wine stains that may be associated with soft tissue hypertrophy. Capillary malformations occur as isolated cutaneous lesions or in conjunction with other abnormalities.

Sturge-Weber syndrome includes ipsilateral association of a facial capillary malformation, almost always involving the V1 distribution of the trigeminal nerve, eye abnormalities (primarily glaucoma), and vascular malformations of the ipsilateral leptomeninges and brain. The incidence of Sturge-Weber syndrome is approximately 5–10% in infants with a capillary malformation of the V1 distribution of the trigeminal nerve. Consequences of Sturge-Weber syndrome may include seizures, developmental delay, hemiplegia, and glaucoma. Neuroimaging may be helpful in demonstrating the characteristic calcifications of the leptomeninges and the abnormal cerebral cortex, although these changes may be quite subtle with early studies. Having MRI findings to diagnose Sturge-Weber syndrome prior to developing symptoms does not necessarily result in better outcomes. Newborns at risk for Sturge-Weber syndrome should have careful clinical follow-ups, including monitoring eye pressure for glaucoma. Early referral to a pediatric neurologist for education of parents to help monitor for neurologic symptoms is also recommended.

Other syndromes associated with capillary malformations include Klippel-Trenaunay syndrome and Parkes-Weber syndrome. Klippel-Trenaunay syndrome is characterized by a capillary malformation, venous and/or lymphatic malformation, and soft tissue and/or bone overgrowth of the affected limb. Parkes-Weber syndrome is the association of arteriovenous malformations, limb overgrowth, and the variable presence of lymphedema and multiple arteriovenous shunts. Klippel-Trenaunay syndrome is a slow-flow capillary-venous malformation, whereas Parkes-Weber syndrome is a fast-flow arterial-venous malformation. Both entities can result in overgrowth and hypertrophy of the affected limb; however, Parkes-Weber syndrome usually results in increased morbidity and clinical consequences.

Treatment of a capillary malformation is best accomplished with the pulsed dye laser. Several treatments are generally required over months to years to achieve desired fading. Depending on the location of the capillary malformation, the response to the pulsed dye laser may be limited. Many experts believe that early initiation of pulsed dye laser therapy results in superior cosmetic results.

Nevus simplex (salmon patch) is the most common vascular lesion in infancy. These lesions consist of ectatic capillaries and are present at birth in about 40% of infants. These pink to red macules can be located on the nape of the neck, glabella, forehead, upper eyelids, and nasolabial regions. More atypical locations include the lateral forehead, nose, upper and lower lip, and back. Unusually persistent or prominent nevus simplex can be associated with Beckwith-Wiedemann syndrome, Nova syndrome, nevus simplex with odontodysplasia, macrocephaly-capillary malformation syndrome, and Roberts-SC syndrome.

No treatment is necessary because most of these fade by 1–2 years of age. Persistent lesions can be treated successfully with the pulsed dye laser if cosmetically disturbing.

Cutis marmorata telangiectatica congenita (CMTC) manifests as an erythematous to dark, bluish-purple, reticulated vascular patch that does not resolve with physiologic warming. This disorder is characteristically more segmental and asymmetric than physiologic cutis marmorata. The clinical findings are most often noted within the first few days of life. Associated features may include cutaneous atrophy and ulcerations of the skin. CMTC has also been reported to be associated with additional abnormalities, including body asymmetry (hypotrophy or hypertrophy of affected limb), other vascular malformations, developmental delay, and glaucoma (with lesions in the V1/V2 trigeminal nerve distribution). CMTC may be difficult to differentiate from a reticulated capillary malformation. The clinical course of CMTC is characterized by gradual fading within the first 1–2 years of life, and treatment is generally not required.

Kasabach-Merritt phenomenon is the presence of thrombocytopenia, hemolytic anemia, hypofibrinogenemia, and consumptive coagulopathy in association with a vascular tumor. Kasabach-Merritt phenomenon is associated with distinct vascular lesions: namely, kaposiform hemangioendothelioma (KHE) or tufted angioma, but not infantile hemangiomas. KHE and tufted angiomas are rare vascular tumors thought to exist on a spectrum. They can be locally destructive, infiltrating underlying soft tissue. Clinical examination findings, histologic findings, and the behavior of associated vascular tumors differ from those of conventional infantile hemangiomas. These lesions are often firm and violaceous with a shiny texture and may proliferate for several years. This condition can be life-threatening and may warrant aggressive multimodal therapeutic modalities. Treatment of choice is complete excision, if possible, but may not be feasible given location, size, or tissue infiltration. Other treatments include sirolimus, high-dose systemic corticosteroids, compression therapy, embolization, irradiation, low-molecular-weight heparin, and interferon alfa. Sirolimus has been used with promising results.

Venous and lymphatic malformations are slow-flow vascular malformations that are often present at birth. Venous malformations are bluish, poorly demarcated, compressible masses. The characteristic bluish hue is caused by the presence of ectatic venous channels in the dermis. Often there may be associated swelling with changes in position or activity. Venous malformations can be segmental or more generalized, and radiologic imaging may assist in determining the extent of the lesion. Evaluation for central nervous system abnormalities with cranial imaging is recommended for patients with venous malformations of the face, to rule out developmental intracranial venous abnormalities that usually are asymptomatic. Many lesions manifest with pain caused by muscle involvement or with episodes of thrombosis or hematoma. Other associated risks include bone abnormalities (thinning, demineralization, or hypoplasia) and chronic localized intravascular coagulation. Treatment is aimed at correcting disfigurement and functional impairments. Therapy can include sclerotherapy, deep laser surgery, compression, and surgical excision. In many cases, it may be best to not intervene and to treat symptomatically.

Lymphatic malformations , previously referred to as lymphangiomas, are usually skin-colored masses that may have superficial clear or hemorrhagic vesicles that occasionally leak lymphatic fluid. These lesions can be classified as macrocystic, microcystic, or mixed. Macrocystic malformations often occur on the head and neck and are frequently diagnosed by prenatal ultrasonography. When such a large lymphatic malformation occurs on the head and neck region, it is often referred to as cystic hygroma. Microcystic malformations are usually more superficial lesions with a “frog spawn” appearance (hemorrhagic and clear vesicles) that intermittently leak lymphatic fluid. This characteristic lesion was previously referred to as lymphangioma circumscriptum. These lesions usually become more evident in childhood rather than infancy. Large lymphatic malformations may impinge on vital structures and cause severe compromise in the neonatal period. Cellulitis is a potential complication of lymphatic malformations and may require prophylactic antibiotics if recurrent. Treatment includes sclerotherapy, sirolimus, and surgery in select lesions; surgical therapy of these lesions is often difficult and may result in recurrences and complications.

Hyperpigmented or Darker Pigmented Lesions

Several hyperpigmented or darker pigmented lesions can be seen during the neonatal period and infancy, while others can present later in childhood ( Table 60.6 ).

Congenital melanocytic nevi (CMN) are pigmented macules, papules, patches, or plaques that are present at birth or early infancy in approximately 2–3% of children. The lesions are often tan at birth and become darker and hairier during infancy and childhood. Congenital nevi can be divided into small (<1.5 cm), medium (1.5–20 cm), large (20–40 cm), and giant (>40 cm) lesions on the basis of their projected adult size. In neonates and infants, lesions larger than 9 cm on the head and larger than 6 cm on the body constitute giant CMN ( Fig. 60.13 ). Most CMN are small to medium in size. The incidence of giant melanocytic nevi is approximately 1/20,000 live births. The majority of CMN have a variant in NRAS .

The malignant potential of CMN remains an area of great controversy. The risk for malignant transformation in the general population for small and medium congenital nevi is thought to be <1%, and there are no universal guidelines for their management. For comparison, the overall risk for melanoma in the general population in the United States is 2%. Removal of these nevi can wait until later childhood, when local anesthesia and outpatient surgery are feasible.

The risk for malignant transformation of giant CMN is another controversial issue. Interestingly, long-term prospective studies have shown melanoma of the central nervous system to be more common than melanoma of the skin. The incidence of melanoma is approximately 8% in those with CMN >60 cm with projected adult size. These large lesions warrant close observation and serial photography. Careful annual or semiannual examinations with palpation of the nevi are essential, as melanoma can arise from deep portions of the nevi with little or no apparent surface alterations. Removal of giant congenital nevi is also controversial from a future-melanoma-risk standpoint. Removal may require extensive grafting as well as soft tissue expansion procedures.

Neurocutaneous melanosis is defined as the presence of giant (>40 cm) and/or multiple CMN, in association with benign or malignant melanocytic infiltration of the leptomeninges. Clinically symptomatic neurocutaneous melanosis substantially worsens the prognosis of large or giant CMN and usually presents around or before 2 years of age, but some may not show symptoms until the second or third decade of life. Most symptomatic patients die within 3 years of the onset of initial neurologic symptoms, typically from central nervous system melanoma or mechanical obstruction. The most frequent clinical manifestations include hydrocephalus, seizures, papilledema, headaches, increase in head circumference, paresis, and developmental delay. Location overlying the axial skeleton and many satellite lesions are predictors of neurocutaneous melanosis.

Screening MRI of the central nervous system is currently the best predictor of all adverse outcomes. MRI with contrast of the head and spine within the first 6 months of life is suggested in newborns with giant CMN, particularly in the posterior axial distribution and especially if satellite nevi are present. An MRI is also recommended for any infant with two or more CMN, regardless of size. MRI abnormalities of the brain have been identified in asymptomatic patients with giant or multiple CMN. The most common imaging abnormalities in asymptomatic patients seen were T1 shortening in the cerebellum, temporal lobes, pons, and medulla. Radiologic findings can be very subtle and may be missed by radiologists unfamiliar with this entity. The risk of melanoma is higher in those with multiple CMN, particularly if neurologic abnormalities are noted on screening MRI.

Café-au-lait macules are well-circumscribed tan macules that usually measure <0.5 cm but may be as large as 15–20 cm in diameter. The lesions are found on any cutaneous site and may be present at birth or appear during early childhood. Although café-au-lait spots are seen in 10–20% of normal individuals, the presence of many macules should raise the clinical suspicion of NF or other genetic disorders (see Table 60.6 ). The presence of six or more café-au-lait spots (>0.5 cm in prepubertal children; >1.5 cm in postpubertal children) fulfills one of the diagnostic criteria for NF-1. Although the lesions are not pathognomonic, they are present in most patients with NF and tend to be larger and more numerous. Café-au-lait spots have also been associated with tuberous sclerosis, McCune-Albright syndrome, Turner syndrome, Bloom syndrome, ataxia-telangiectasia, Russell-Silver syndrome, Fanconi anemia, epidermal nevus syndrome, Gaucher disease, and Chédiak-Higashi syndrome.

Dermal melanocytosis (mongolian spots) are large, poorly demarcated, slate-gray to blue-black patches usually located over the buttocks or lumbosacral region of normal infants. The condition occurs in approximately 80–90% of Black infants, 75% of Asian infants, and 10% of White infants. Dermal melanocytosis may be single or multiple and frequently measure up to 10–20 cm in diameter. This benign disorder is present at birth, usually fades during early childhood, and necessitates no therapeutic intervention. In rare cases, the lesions may persist into adulthood and may benefit from therapy with lasers that treat dermal pigmentation. These lesions should not be confused with bruises. Dermal melanocytosis is also seen in Hurler, Hunter, GM1 gangliosidosis, Niemann-Pick, mucolipidosis, and mannosidosis syndromes.

The nevus of Ota and nevus of Ito are special variants of dermal melanocytosis commonly seen in Asian and Black individuals. In contrast to mongolian spots, these conditions tend to persist throughout adulthood. The nevus of Ota is a slate-gray to blue-black patch located in the distribution of the trigeminal nerve. The condition is usually unilateral and involves the forehead, temple, periorbital region, nose, and cheek. Pigmentation of the sclera, iris, and choroid occurs in about 50% of affected individuals. The disorder may be cosmetically disfiguring, and laser treatment may be promising in some cases. The nevus of Ito is a similar lesion occurring in the distribution of the lateral supraclavicular and brachial nerves. The condition is usually unilateral and involves the shoulder, neck, upper arm, scapular, and/or deltoid regions. It may be seen alone or in conjunction with the nevus of Ota.

Hypopigmented and Depigmented Lesions

These conditions are often cosmetically disfiguring and persistent. They can be markers of serious systemic diseases. Pigmentary disorders may be localized or generalized; congenital or acquired; and transient, stable, or progressive ( Table 60.7 ).

Nevus depigmentosus is a benign, solitary, hypopigmented macule or patch that is noted at birth. It is not depigmented as the name suggests. It typically remains stable in size and may grow in proportion to the patient as they grow. It should be differentiated from vitiligo.

Ash leaf spots are hypopigmented macules, sometimes present at birth or within the first few months or years of life, that allow early identification of individuals with tuberous sclerosis ( Fig. 60.14 ). Although occasionally observed in normal infants, the characteristic lesions are present in up to 90% of patients with tuberous sclerosis. They are usually 2–3 cm in size and are located on the trunk and extremities. The macules may be lancet shaped or may have a confetti-like or irregularly shaped appearance. Wood lamp examination may facilitate identification . Although tuberous sclerosis is an autosomal dominant disorder, spontaneous gene variants are responsible for up to 50% of new cases. Other cutaneous findings include facial angiofibromas (adenoma sebaceum), periungual or subungual fibromas, gingival fibromas, shagreen patches (connective tissue hamartomas), and fibrous plaques (typically on the forehead). Systemic manifestations include seizures, intellectual disability, cardiac rhabdomyomas, renal angiomyolipomas and cysts, retinal nodular hamartomas, and pulmonary cysts. Imaging studies of the brain may demonstrate cortical tubers or subependymal nodules, which are pathognomonic for tuberous sclerosis.

Piebaldism is characterized by circumscribed areas of depigmentation in the newborn. The leukoderma is usually located on the frontal scalp and is associated with a white forelock; however, the depigmented patches characteristically involve the trunk, upper arms, and legs. Hyperpigmented or normally pigmented macules or patches may occur within the depigmented patches. This rare condition is transmitted in an autosomal dominant pattern. The disorder is usually present at birth but may not be recognized until later because of the light color of neonatal skin. A Wood lamp may enhance the contrast between depigmented and normal skin.

Piebaldism is a stable condition throughout life, and most affected individuals are otherwise normal. Sun protection and cosmetic camouflage of the depigmented skin are the mainstays of therapy.

Waardenburg syndrome is a rare genetic disorder characterized by a white forelock, areas of leukoderma, congenital sensorineural deafness, heterochromia of the irides, and lateral displacement of the medial canthi. Other features may include a flattened nasal bridge, confluent eyebrows, hypoplasia of the nasal alae, speech impairment that may or may not be related to presence of a cleft lip or palate, and various skeletal abnormalities. It is most commonly inherited in an autosomal dominant fashion, though autosomal recessive inheritance patterns are sometimes seen.

Albinism is manifested by diffuse congenital hypopigmentation or depigmentation of the skin, hair, and eyes. This heterogeneous group of disorders is composed of approximately 10 types of oculocutaneous albinism and 5 forms of ocular albinism. Most types of oculocutaneous albinism are inherited in an autosomal recessive pattern. The variants of ocular albinism are transmitted in an X-linked or autosomal recessive mode of inheritance.

The various forms of albinism can usually be diagnosed by findings on physical examination. These features include absent or reduced pigmentation of skin and hair and ophthalmologic findings such as foveal hypoplasia, nystagmus, photophobia, transillumination of the irides, fundal depigmentation, and decreased visual acuity. Patients should be monitored closely by ophthalmologists and evaluated for hearing loss. In White persons, the skin is usually milk white and the hair is white, blond, or light brown. The pupils are usually pink, and the irides are blue or gray. In African-Americans, the skin may appear tan or white and is frequently freckled. The hair is usually blond or red, and the eyes are blue or hazel.

Treatment of albinism includes photoprotection and sun avoidance. Individuals are predisposed to severe actinic damage and should be monitored closely for the development of actinic keratoses, basal cell carcinomas, squamous cell carcinomas, and melanomas.