Vascular Birthmarks

Pediatric vascular anomalies are subdivided into vascular tumors and vascular malformations.

• Vascular tumors are characterized by cellular hyperplasia and disordered growth. Infantile hemangiomas are the most common vascular tumor of childhood; other examples include pyogenic granuloma, congenital hemangioma, kaposiform hemangioendothelioma, and tufted angioma.

• Vascular malformations are static abnormalities that derive from structures including capillaries, veins, arteries, and lymphatics. Although these malformations are congenital, they may not be visible at birth and enlarge over time without regression. Examples of vascular malformations include capillary and venous malformations. Some vascular malformations are associated with syndromes.

Nevus Simplex

Nevus simplex (also known as a salmon patch) is a benign capillary malformation found in 30% to 80% of neonates. It presents as a dull, pink-red patch, commonly located on midline locations of the glabella, forehead, posterior neck, upper eyelids, and back. “Nevus simplex complex” refers to multiple patches in an infant. Although nevus simplex is usually an isolated finding, it can be associated with syndromes (e.g., Beckwith-Wiedemann syndrome). Treatment is not necessary because the majority of these capillary birthmarks fade within 1 to 2 years. The exception is lesions located on the posterior neck, which tend to be persistent.

Subtle pink-red patches, commonly on the midline face. (Photograph courtesy of Carol Cheng, MD.)

Capillary Malformation

Capillary malformation (also known as port-wine stain or port-wine birthmark [PWB]) is a vascular malformation comprised of dermal capillaries. The estimated incidence is 3 to 5 per 1000 people and is generally congenital (rarely it may be acquired). PWB presents as a well-circumscribed pink-to-dark-red vascular patch, most often on the face. Unlike nevus simplex, PWB does not tend toward resolution and will darken over time. PWB may develop superficial vascular blebs and can have associated bone and soft tissue deformities of underlying structures.

(Source: The image on the left is from the Massachusetts Medical Society. The image on the right is from VisualDx.)

Treatment: The gold standard for treatment of capillary malformation is treatment with pulsed-dye laser. Repeated treatments are often required, and treatment in the first year of life results in better outcomes. For refractory cases, second-line treatments include neodymium:yttrium-aluminum-garnet (Nd:YAG) and alexandrite lasers, but these are associated with higher risk of scarring. See recent consensus statement on management and treatment.

Sturge-Weber syndrome is associated with PWB, although only a small percentage of patients with PWB have Sturge-Weber syndrome. The risk for Sturge-Weber syndrome in a patient with PWB is greater when the facial capillary malformation is present on the upper forehead and highest when the malformation is bilateral.

Characteristics of Sturge-Weber syndrome:

• facial capillary malformation

• ipsilateral ocular abnormality (e.g., diffuse choroidal hemangiomas, glaucoma, and anterior chamber malformations, all of which may impact vision)

• central nervous system abnormality

Representative photographs and magnetic resonance imaging (MRI) scans from study participants with the Sturge-Weber syndrome or isolated port-wine stains. (Source: Sturge-Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ. N Engl J Med 2013.)

Infantile Hemangiomas

Infantile hemangiomas (IH) are the most common vascular tumor of childhood, affecting an estimated 4% to 5% of infants. IH are distinguished from other vascular tumors and from vascular malformations by unique characteristics, including:

• development during the first weeks or months of life

• natural history of rapid growth followed by stabilization then involution by age 4 years

• unique immunohistochemical staining pattern on biopsy

The exact mechanism of IH formation is unclear but may be related to tissue hypoxia triggering growth of hemangioma endothelial cells.

Risk factors for the development of IH include:

• female sex

• multiple-gestation pregnancy

• preterm birth

• low birth weight

• white, non-Hispanic ethnicity

• prenatal complications (older maternal age, placenta previa, preeclampsia)

• family history of infantile hemangioma

Presentation: In most cases, IH present as a solitary lesion. However, as many as 20% to 30% of patients have multiple infantile hemangiomas. IH can be classified by both the depth of soft-tissue involvement and by the distribution of the IH.

• Classification based on the depth of soft-tissue involvement:

  • superficial

  • deep

  • combined (mixed)

A superficial hemangioma (formerly referred to as “strawberry” hemangioma). (Photo courtesy of Carol Cheng, MD.)

Deep infantile hemangioma present as a skin-colored-to-bluish nodule. Occasionally, lesions will have both superficial and deep features. (Photograph courtesy of Carol Cheng, MD.)

• Classification based on distribution:

  • focal (localized): discrete, arising from a single focus

  • segmental: covering a segment or regional area that is determined by embryonic neuroectodermal units

  • indeterminate: not easily classified as focal or segmental

  • multifocal: arising from multiple foci

A focal periocular hemangioma in an infant that resulted in astigmatism. (Source: Hemangiomas in Children. N Engl J Med 1999.)

The smaller hemangioma will probably resolve with virtually no scarring of the skin, whereas the large, exophytic lesion carries a risk of considerable fibrofatty residua. (Source: Hemangiomas in Children. N Engl J Med 1999.)

Natural history: Nearly all IHs are characterized by the following phases:

• proliferation

• stabilization

• slow involution

Many IH are diagnosed between ages 5 to 8 weeks with the most rapid growth during the first months of life. Growth of IH is completed by 3 months of age in 80% of infants, suggesting the need for early referral if treatment is desired.

Differential diagnosis for IH:

• capillary malformation

• congenital hemangioma

• kaposiform hemangioendothelioma

• tufted angioma

• subcutaneous tumor

• venous malformation

High-risk IH: In 2019 the American Academy of Pediatrics (AAP) released clinical practice guidelines to help providers recognize high-risk IH that may require further evaluation or early intervention. The AAP guidelines indicate that IHs are considered high risk if there is evidence of or potential for the following:

• life-threatening complications

• functional impairment or risk thereof

• ulceration or risk thereof

• structural anomalies

• permanent scarring or distortion of anatomic landmarks

The Infantile Hemangioma Referral Score (IH-Res score) is a scoring system to help clinicians determine which infants with IH should be referred to pediatric dermatology for further evaluation.

High-risk IHs on face and neck:

• IH on the eye may affect vision and cause disfigurement.

• IHs on the lip, neck, or diaper area are at increased risk for ulceration.

• IHs on nose and ears are at high risk for disfigurement or permanent distortion due to cartilage deformity.

• Facial segmental IH are at high risk of scarring and associated with structural anomalies (e.g., PHACE syndrome).

PHACE syndrome is a neurovascular syndrome that should be suspected in the presence of a large (>5 cm), segmental IH, particularly when located on the face, scalp, and neck. In a recent study, high-risk features associated with PHACE syndrome were IH that involved 3 or more locations and a surface area ≥25 cm².

PHACE syndrome is defined by the presence of a large, segmental hemangioma and one or more of the following congenital malformations:

• P — posterior fossa anomalies

• H — hemangioma

• A — arterial anomalies

• C — cardiac anomalies

• E — eye anomalies

• S — sternal anomalies, supraumbilical raphe

Beard distribution: IH in the beard distribution should be evaluated for airway hemangiomas.

High-risk IHs on trunk, extremities, and perineum:

• Segmental IHs in the extremities are at higher risk of ulceration and permanent skin changes.

• Perineum IHs are at high risk of ulceration.

• Multiple (≥5) cutaneous hemangiomas are associated with visceral hemangiomas, most commonly of the liver. Screening via abdominal ultrasound is recommended. Hypothyroidism, due to excessive iodothyronine deiodinase expression, may occur in patients with multiple or large and segmental infantile hemangiomas.

High-risk IHs involving the posterior trunk:

• Small lesions on torso are lower risk.

• Sequential lumbosacral or perineal IH are at higher risk of ulceration and may be associated with structural anomalies (e.g., LUMBAR syndrome).

LUMBAR syndrome refers to the association between large, segmental lower-body IH and underlying developmental abnormalities. MRI and renal ultrasound are recommended in infants and older children with a segmental hemangioma over the lumbosacral spine.

• L — lower-body IH and other cutaneous defects

• U — urogenital anomalies/ulceration

• M — myelopathy

• B — bony deformities

• A — anorectal malformations/arterial anomalies

• R — renal anomalies

Treatment: Although the majority of IHs will not require treatment, early referral (ideally within the first 8 weeks of life) to a specialist is paramount for high-risk hemangiomas.

• Propranolol

  • The systemic agent of choice for treatment of IH, a randomized, placebo-controlled study demonstrated the efficacy of propranolol for treatment of IH, with infrequent adverse effects.

  • This nonselective beta1 and beta2 antagonist is postulated to act through several mechanisms in the treatment of IH (including vasoconstriction, angiogenesis inhibition, induction of apoptosis, inhibition of nitric oxide production, regulation of the renin-angiotensin system).

  • Inpatient initiation of therapy is recommended for infants younger than 5 weeks, infants with cardiovascular or respiratory comorbidities, and those with poor social support.

  • Propranolol should be given with or shortly after feeding and should be withheld during times of poor oral intake to avoid hypoglycemia. Routine blood glucose monitoring is not required.

  • Adverse effects:

    • bradycardia

    • sleep disturbance

    • bronchial irritation

    • hypotension

    • cold extremities

• Topical timolol maleate

  • This nonselective beta-adrenergic-receptor inhibitor can be used to treat small focal thin superficial infantile hemangiomas

  • Although timolol is a topical treatment, it can be absorbed systemically and adverse events have been reported.

• Adjuvant treatments include:

  • systemic and intralesional steroids

  • pulsed-dye laser (PDL)

  • surgical excision