CAPILLARY STAIN (SALMON PATCH)

SYNONYMS Nevus simplex, telangiectatic nevus, “stork bite,” nuchal nevus, Unna’s nevus, evanescent macule, angel kiss, or aigrette.

EPIDEMIOLOGY

AGE Present at birth, fades with time.

GENDER M = F.

INCIDENCE Occurs in 30% to 40% of newborns.

ETIOLOGY Thought to be a persistence of fetal circulation, gradually becomes less prominent.

HISTORY

Present at birth, these benign lesions fade with time. In lighter skin types, the patch may be more persistent or evident during episodes of crying or physical exertion. Fifty percent of salmon patches in the nuchal region persist for life. They are asymptomatic and benign.

PHYSICAL EXAMINATION

Skin Findings

TYPE Macular with telangiectasias.

COLOR Dull pink to red.

DISTRIBUTION Head and neck.

SITES OF PREDILECTION Nape of neck (22%), glabella (20%) (Fig. 8-1A), and eyelids (5%).

DIFFERENTIAL DIAGNOSIS

Salmon patch is the most common vascular birthmark. Its classic locations and self-resolving tendencies should differentiate it from other vascular birthmarks such as capillary malformations and hemangiomas.

LABORATORY EXAMINATIONS

HISTOPATHOLOGY Skin biopsy reveals dilated dermal capillaries.

COURSE AND PROGNOSIS

Facial salmon patches fade with time (Fig. 8-1B) and only become evident in lighter skin types with crying or physical exertion. Nuchal salmon patches can persist but are asymptomatic and not usually of cosmetic concern because they are covered by the posterior hairline.

MANAGEMENT

Unlike capillary malformations, facial salmon patches fade almost completely and usually do not require treatment. Persistent lesions can occur in the nuchal area, but these are typically covered with hair and not a cosmetic concern. Rare bothersome persistent lesions can be treated with laser ablation.

CAPILLARY MALFORMATIONS (PORT-WINE STAIN) AND ASSOCIATED SYNDROMES

SYNONYMS Nevus flammeus, telangiectasia.

EPIDEMIOLOGY

AGE Present at birth, persists throughout life.

GENDER M = F.

RACE Whites > Asians > blacks.

ETIOLOGY Mutation in vascular morphogenesis.

PATHOPHYSIOLOGY

Given the occasional association of a PWS with Sturge–Weber or Klippel–Trenaunay syndromes (Table 8-1), it is postulated that the PWS is caused by a mutation in the anterior neural crest or mesoderm during embryogenesis. Activating mutations in the gene GNAQ have been linked with both PWSs and the Sturge–Weber syndrome.

PHYSICAL EXAMINATION

Skin Lesions

TYPE Infancy: macular. Adulthood: nodular, plaque-like.

COLOR Infancy: pink. Adulthood: red, purple.

SHAPE Segmental. Large lesions follow a dermatomal distribution and rarely cross the midline (Fig. 8-2A).

DISTRIBUTION Localized or diffuse. Most commonly involve the face in a trigeminal nerve distribution (V1, V2, or V3).

DIFFERENTIAL DIAGNOSIS

The diagnosis of a PWS is made clinically. The differential diagnosis of a PWS includes a hemangioma, salmon patch, venous malformation, lymphatic malformation, or arteriovenous malformation. Doppler ultrasound, CT, MRI, or other imaging studies may be needed if the diagnosis is unclear.

LABORATORY EXAMINATIONS

HISTOPATHOLOGY Dilated capillaries and increased ectasias in the deep reticular dermis.

IMMUNOHISTOCHEMISTRY GLUT-1-negative, differentiating PWS from hemangiomas.

COURSE AND PROGNOSIS

PWS do not regress spontaneously. The area of involvement tends to increase in proportion to the size of the child. In adulthood, PWS can turn darker red–purple in color and thicken, which leads to more severe cosmetic disfigurement. In some cases, the thickening is associated with hyperplastic skin changes and asymmetric overgrowth of the area underlying the PWS (face > trunk and limbs).

MANAGEMENT

Isolated PWS are benign but can be disfiguring and distressing to the patient. Multiple treatments with a pulsed dye laser are very effective and should be considered in childhood before the lesion progresses to a more severe nodular, disfiguring form. Alternatively, a PWS can be covered up with makeup.

The majority of PWS have no associated abnormalities. Infrequently, a midline PWS of the lumbosacral, back, or nape area may be a hallmark for spinal dysraphism especially if seen in conjunction with other skin signs (pit, dimple, sinus, fibroma, lipoma, or hypertrichosis). Dysraphism can be detected with ultrasound or MRI.

Rarely, PWS can be associated with Sturge–Weber syndrome (Fig. 8-2B) or Klippel– Trenaunay syndrome (Table 8-1). It is estimated that 10% to 15% of infants with a V1 PWS will develop the ocular glaucoma and neurologic seizures of Sturge–Weber syndrome. The risk of Sturge–Weber is increased with multiple dermatomal involvement (e.g., V1, V2, and V3) or with bilateral PWSs. If suspected, internal imaging with radiography (calcifications), CT (cortical and leptomeningeal brain lesions), MRI (myelination), SPECT (blood flow), or PET (glucose metabolism) may be helpful. Klippel–Trenaunay syndrome is the association of limb hypertrophy with an overlying PWS and venous malformation or varicosity. Again, Doppler ultrasound or MRI can better detect the extent of tissue involvement in these patients.

HEMANGIOMAS AND ASSOCIATED SYNDROMES

SYNONYMS Infantile hemangioma, hemangioma of infancy, strawberry nevus, angioma cavernosum, capillary hemangioma.

EPIDEMIOLOGY

AGE Rarely present at birth, but arise in the first weeks to months of life.

GENDER F > M, 5:1

PREVALENCE Seen more in premature infants (<30 weeks gestational age or birthweight < 1,500 g), infants of mothers’ status postchorionic villus sampling, infants of older mothers, and infants of multiple gestation.

RACE More common in Caucasians.

INCIDENCE Most common tumor of infancy. Seen in 2.6% of all newborns. Occur in 10% to 12% of Caucasian infants, with nearly all present by age 1 year.

ETIOLOGY Abnormally increased vascular proliferation. Reports of familial cases with autosomal dominant inheritance.

PATHOPHYSIOLOGY

Hemangiomas are localized proliferations of blood vessels. Extensive study is underway to understand the signaling mechanisms that cause this benign tumor to grow, plateau, and then spontaneously involute. Several proposed mechanisms for hemangioma formation include the following:

1. A mutation in endothelial cells,

2. A mutation in other cells influencing endothelial proliferation,

3. Placental origin of proliferative cells, and/or

4. Dysregulation of immature endothelial progenitor cells.

It seems that a combination of these mechanisms, multiple genes, and local effects all influence the development, growth, and involution of hemangiomas. Endothelial cells from infantile hemangiomas stain positive for GLUT1, a specific glucose transporter, though its exact role in the pathogenesis of infantile hemangiomas remains to be determined.

HISTORY

Lesions present soon after birth during the first few weeks of life (Fig. 8-3A). The lesions proliferate 6 to 18 months (Fig. 8-3B), and then spontaneously involute, typically by age 9 years (Fig. 8-3C). Thirty percent of lesions involute by age 3, 50% by age 5, 70% by age 7, and 90% by age 9. At the end of involution, most lesions are cosmetically undetectable, but a few can leave atrophic, fibrofatty, or telangiectatic markings. Rarely, a hemangioma proliferates in utero, is present at birth, and undergoes rapid spontaneous resolution (“rapidly involuting congenital hemangioma” or “RICH”) in the first year of life. Even more rare is a noninvoluting congenital hemangioma (“NICH”), which will not go away spontaneously. Both of these latter hemangioma variants are the exception rather than the rule.

Solitary hemangiomas are asymptomatic, benign, and rarely bleed. Possible complications include the following:

1. Ulceration (seen in 10% of hemangiomas, Fig. 8-3B), most common on lip, neck, or anogenital locations.

2. Location near critical structures (periorbital, nasal tip, lip, pinna, breast, and anogenital area) causing obstruction.

3. Association with internal abnormalities (CNS, laryngeal obstruction, and spinal dysraphism).

PHYSICAL EXAMINATION

Skin Findings

TYPE Nodule, plaque, may be ulcerated.

COLOR Superficial: pink, red. Deep: blue– purple. Involuting: white/gray.

FREQUENCY 50% to 60% superficial, 25% to 35% combined, 15% deep.

SIZE Average 2 to 5 cm but can grow up to 20 cm in size.

PATTERN Focal or segmental.

PALPATION Superficial lesions are soft/compressible; deeper lesions are more firm.

SITES OF PREDILECTION Face, trunk, legs, oral, and genital mucous membranes.

DIFFERENTIAL DIAGNOSIS

Hemangiomas are sometimes confused with other vascular abnormalities such as capillary malformations, infantile myofibromatosis, or pyogenic granulomas. Deeper lesions can mimic dermal or subcutaneous masses such as fibrosarcoma, rhabdomyosarcoma, neuroblas toma, dermatofibrosarcoma protuberans, nasal glioma, lipoblastoma, venous, lymphatic, or AV malformations. The characteristic proliferative and involuting phase can clinically differentiate hemangiomas from other vascular lesions. Radiographic studies or histologic examination may be necessary in most difficult cases.

LABORATORY EXAMINATIONS

HISTOPATHOLOGY Proliferating: endothelial cell hyperplasia, lobule formation, mast cells, and prominent basement membrane. Involuting: fibrofatty tissue, decreased mast cells.

IMMUNOHISTOCHEMISTRY GLUT1-positive staining differentiates infantile hemangiomas from all other vascular malformations.

DOPPLER EVALUATION Can determine slow flow hemangiomas versus fast flow AV malformations.

CT SCAN Uniformly enhancing soft tissue mass with dilated feeding and draining vessels.

MRI Soft tissue mass which is iso- or hypointense to muscle with flow voids.

COURSE AND PROGNOSIS

Hemangiomas spontaneously involute by age 5 to 9 years. The residual skin changes are barely detectable but can include skin atrophy, fibrofatty tissue, telangiectasia, or depigmentation (Fig. 8-3C). Typical spontaneous involution leaves the best cosmetic results, and thus nonintervention in uncomplicated lesions is recommended.

Focal hemangiomas are typically small, arise from one locus and spontaneously involute without any complications. Larger segmental hemangiomas may be associated with systemic anomalies such as spinal dysraphism, GI or GU anomalies, or PHACES syndrome (Table 8-2).

A midline hemangioma of the lumbosacral, back, or nape area may be a hallmark for spinal dysraphism especially if seen in conjunction with other skin signs (pit, dimple, sinus, fibroma, lipoma, or hypertrichosis) or other malformations (imperforate anus, GI fistulae, skeletal, and renal abnormalities). An MRI can detect these underlying defects. Hemangiomas in this region have been associated with the LUMBAR and PELVIS syndromes as well (Table 8-2).

Ten to twenty-five percent of patients will have multiple hemangiomas, and numerous cutaneous hemangiomas can be a marker for internal involvement. A child with numerous cutaneous hemangiomas should be evaluated for the possibility of hemangiomas of the visceral organs, GI tract, liver, CNS, lungs, mucous membranes, or eyes. Complications include high-output cardiac failure, GI bleeding, hydrocephalus, visceral hemorrhage, and ocular abnormalities. Radiologic evaluation (ultrasound, CT, or MRI) may be helpful in determining the extent of internal involvement. Infants with large or multiple hemangiomas should also be screened for hypothyroidism due to overproduction of type III iodothyronine deiodinase.

MANAGEMENT

Treatment for the majority of simple hemangiomas is unnecessary because they are asymptomatic and self-resolve with a good cosmetic result.

Less than 2% of hemangiomas require intervention (for ulceration/bleeding, blocking facial structures or GI/GU tracts). Ulcerations can be managed with local wound care: saline soaks, topical antibiotics (mupirocin or metronidazole), and occlusive dressings. Pain associated with the ulcers can be alleviated with oral acetaminophen. Superinfected lesions may require a course of oral antibiotics (such as a first-generation cephalosporin).

Intralesional steroids can be used to treat small hemangiomas, but periocular injections can be complicated by ophthalmic artery occlusion and can lead to blindness. Topical steroids are safer, but their efficacy is unclear. Topical 5% imiquimod cream reportedly helps proliferating hemangiomas, but the cream can cause erosions as a complication.

Over the last decade, the use of systemic and topical beta blockers for the treatment of infantile hemangiomas has become increasingly prevalent for large, ulcerating, or high-risk hemangiomas. Systemic propranolol has been demonstrated to be effective and well-tolerated for the management of infantile hemangiomas. Dosing of 3 mg/kg/d of propranolol for 24 weeks has demonstrated efficacy in complete resolution of hemangiomas in the majority of patients; some may require a second or prolonged course. Doses of 1 to 3 mg/kg/d in divided doses have shown efficacy in smaller series. Adverse reactions associated with propranolol use include bradycardia, hypoglycemia, and bronchospasm. The use of topical beta blockers including timolol has also been explored for the management of infantile hemangiomas with promising results. Systemic steroids, such as prednisolone or prednisone, are used for life-threatening obstructive hemangiomas; 2 to 3 mg/kg/d is recommended until cessation of hemangioma growth or shrinking is achieved, followed by steroid taper. Adverse reactions to systemic steroid include cushingoid facies, irritability, GI symptoms, and decreased growth rate.

Systemic IFN-α (angiogenesis inhibitor) can be used for refractory, severe life-threatening hemangiomas at a dose of 1 to 3 million U/m²/d injected subcutaneously. Adverse effects include spastic diplegia, fever, irritability, diarrhea, neutropenia, elevated LFTs, and skin necrosis. Systemic vincristine is a chemotherapy approach for resistant life-threatening hemangiomas, but its effectiveness is unclear. Adverse effects include peripheral neuropathy, jaw pain, anemia, and leukopenia.