Capillary Malformation 

Updated: Nov 08, 2019
Author: Richard J Antaya, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Capillary malformation, usually referred to as a port-wine stain or nevus flammeus, is the most common type of vascular malformation. As a congenital malformation of the superficial dermal blood vessels, capillary malformation is present at birth and grows in size commensurate with the child; capillary malformations remain present for life and have no tendency toward involution. A rare form of capillary malformation that is not present at birth is referred to as an acquired capillary malformation; however, this article focuses on the more common congenital lesion.

Past nosology of this lesion has resulted in much confusion, and an excessive number of descriptive terms have been applied to it. Confusion originated from difficulty in differentiating vascular malformations from vascular proliferative lesions, such as hemangiomas, and from the use of wholly clinical descriptions in categorizing these lesions. According to the International Society for the Study of Vascular Anomalies (ISSVA) classification, vascular malformations are classified according to their predominant vessel type, such as arterial, venous, lymphatic, capillary, or complex (a combination of different vessels).[1]

Although some capillary malformations may be associated with other vessel malformations, most occur alone as venulocapillary malformations. Happle contends that the term capillary malformation should be used as a more generalized designation for several congenital disorders of dilated capillaries (eg, angiokeratomas, nevus anemicus, cutis marmorata telangiectatica congenita).[2] While this notion has merit, the accepted nomenclature is that capillary malformation be reserved for a patch of red-colored skin, historically referred to as a port-wine stain or a nevus flammeus.

Pathophysiology

Capillary malformations and other vascular malformations are the result of abnormal morphogenesis. Capillary malformations are characterized by ectatic papillary dermal capillaries and postcapillary venules in the upper reticular dermis, with some evidence of increased vessel density and no apparent proliferation of vessels. These ectatic vessels are lined by flat, benign-appearing endothelial cells, similar to the vessels of normal skin, with similar staining characteristics for endothelial antigens, including fibronectin, von Willebrand factor, and collagenous basement membrane proteins. The endothelial cells also exhibit cell turnover similar to normal vessels, supported by a paucity of mitoses or an uptake of tritiated thymidine. One study demonstrated a mean vessel depth of 0.46 mm in capillary malformations, suggesting that most of the vessels are superficial.

Evidence supports a neural role in both the development and progression of capillary malformations. Animal studies show that the sympathetic nervous system influences the composition and functional properties of the vessel wall during development.

Immunohistochemical studies of capillary malformations reveal a significantly decreased density of perivascular nervous tissue in lesional skin, suggesting that inadequate innervation may be in part responsible for decreased vascular tone and progressive vascular dilatation.[3] Confocal microscopic studies demonstrate an inverse correlation between nerve density and blood vessel diameter and evidence that capillary malformations with the lowest nerve density exhibit the highest blood vessel density and the poorest response to laser intervention.[4] The finding of increased vessel diameter and/or decreased nerve density may be secondary to other factors, such as local cytokine production or abnormal receptors; however, this has not been elucidated.

The potent endothelial cell mitogen vascular endothelial growth factor (VEGF)–A and its most active receptor VEGF-R2 expression are significantly increased in capillary malformation skin tissue compared with control skin.[5] This may suggest that VEGF and VEGF-R could contribute to the pathogenesis of capillary malformations by inducing vessel proliferation and/or vasodilatation. If this is indeed a pathogenic factor, antiangiogenic treatments using VEGF blocking agents may prove to be useful for capillary malformations. Conversely, one report describes expansion of a biopsy-proven capillary malformation following partial surgical excision in an adult in whom the newly expanded capillary malformation expressed marked elevations of both tyrosine kinase receptor (Tie2) and its ligand angiopoietin-1 and no increase in VEGF.[6] Tie2 and angiopoietin-1 are known regulators of vascular remodeling during angiogenesis, mutations of which have been demonstrated in familial venous malformations.

A somatic activating mutation encoding a p.Arg183Gln amino acid substitution in GNAQ, a q class of G-protein alpha subunits that mediates signals between G-protein–coupled receptors and their downstream effectors, has been shown to be the etiology of capillary malformations.[7] This specific mutation was found in both lesional skin of nonsyndromic capillary malformations and in the lesional skin and affected brain tissue of patients with Sturge-Weber syndrome (SWS). Additionally, the endothelial cells of capillary malformations possess a higher density of the GNAQ mutation than other cells in the affected tissue.[8] Other mutations in this G-protein have been identified in blue nevi, nevus of Ota, and in uveal melanoma. This helps explain the occurrence of both melanocytic nevi and capillary malformations co-localizing to the same area in phakomatosis pigmentovascularis. This G protein is in the MAP/MEK cell proliferation pathway. It has been posited that the timing of the mutation explains the tissue involvement and severity of the condition, with an earlier mutation occurring in SWS and a later one in nonsyndromic capillary malformations.

An inactivating mutation of RASA1 on 5q has been detected in some kindreds with multiple, small, round-to-oval, pink capillary malformations.[9] RASA1 encodes a GTPase-activating protein, which negatively regulates Ras activity. These kindreds all had members who also had arteriovenous malformations (AVMs) or arteriovenous fistulae (AVFs). This disease has been coined capillary malformation-AVM syndrome to denote the 2 types of vascular malformations observed in these kindreds. One kindred with a novel RASA1 -inactivating mutation included a member with a large lower extremity capillary malformation with associated ipsilateral limb enlargement[10] ; however, another large kindred has been identified that has only capillary malformations and no evidence of AVMs or AVFs, suggesting that RASA1 mutations may be implicated more often than previously believed.[11]

Use of transcutaneous videomicroscopy and handheld dermoscopy reveals two distinct patterns of vascular ectasia in capillary malformations. The type 1 abnormality is composed of superficial, tortuous, dilated end-capillary loops in the superficial papillary dermis. The type 2 abnormality consists of dilated, ectatic vessels in the superficial horizontal vascular plexus. Some patients exhibit a combination of both abnormal patterns. Evidence suggests that the type 1 abnormality has a better response to 585-nm flashlamp-pumped pulsed-dye laser (PDL) therapy than the type 2 abnormality.[12] Moreover, one study found a correlation between the depth and pattern of the capillary malformations and the location of the lesions, demonstrating improved responses to laser therapy with locations demonstrating a type 1 pattern (V3 region of the face, neck, and trunk).

Etiology

There is strong evidence associating postzygotic somatic activating mutations in the gene GNAQ to capillary malformations from both nonsyndromic capillary malformations and those associated with Sturge-Weber syndrome.[7] This may account for some of the observed mosaic and twin-spotting phenotypes.[13] Capillary malformations have also demonstrated a neural deficiency of sympathetic innervation of the superficial dermal blood vessels.[3]

Epidemiology

Frequency

United States

Capillary malformation occurs in 0.3-0.5% of newborns.

International

Worldwide, capillary malformation occurs in 0.1-2% of newborns.

Race

According to at least one survey, capillary malformations are more common in whites than in African Americans.[14]

Sex

The sex distribution of capillary malformations is equal.

Age

Capillary malformations are present at birth. Some lesions may not be readily observed at birth because of anemia or plethora. In certain lesions, some lightening of the lesions may occur during the first year of life; however, beyond that time, further lightening is generally not observed.

The very rare acquired port-wine stain can occur at any age after birth and is identical to congenital capillary malformations both clinically and histologically. The etiology of these lesions is unknown and most are idiopathic; however, trauma, chronic UV exposure, hormonal influences, infections, solid brain tumor, and various internal vascular disorders have been implicated.[15]

Prognosis

Isolated capillary malformations do not appear to cause an increase in mortality; however, psychosocial disability secondary to facial disfigurement can be overwhelming. Several studies demonstrate that patients with facial capillary malformations exhibit greater self-concern, ruminative self-doubt in interpersonal interactions, social inhibition, isolated and passive orientation in interpersonal relationships, stigmatization from society, and limitations of privileges and opportunities otherwise afforded to those without facial disfigurement. One study demonstrated that the psychosocial difficulties not only persisted but actually worsened in adulthood.[16]

Development of lobulated capillary hemangiomas (pyogenic granulomas) within capillary malformations often results in bleeding.[17, 18] The destruction of these lesions usually results in minor scarring of the skin.

Any morbidity involved with capillary malformations is associated with more extensive vascular malformations.

Patient Education

Patients and parents benefit from an organized, informative, multidisciplinary effort to address psychological, medical, and surgical needs for optimal outcomes from medical care, especially surgical or laser procedures.

In the author's experience, a frank discussion with the affected child's classmates early in the school year is most beneficial. A brief classroom discussion, which can be facilitated by the patient's parent or teacher, offers an opportunity to educate the child's classmates about the birthmark and to reassure them that it is neither painful nor contagious. Once the capillary malformation has been explained adequately and questions answered, most children cease to further question the child. This helps to alleviate some of the patient's psychological burden.

Buddy Booby's Birthmark, by Evan Ducker, a child with a capillary malformation, and his mother, Donna Cardenia Ducker, is a children's picture book depicting a baby booby bird on the Galapagos Islands that was born with a capillary malformation (birthmark) on his beak. It is the first children's book of its kind to depict the social stressors associated with facial capillary malformations. It is available for purchase at http://www.amazon.com/Buddy-Boobys-Birthmark-Donna-Ducker/dp/0979441315.

 

Presentation

History

Nearly all cases of capillary malformation can be diagnosed by taking a careful history and performing a physical examination.

Onset

Capillary malformations are always present at birth, but they may not be apparent early in life because of neonatal anemia or plethora.

Location

Of capillary malformations, most involve the head and the neck. Of facial capillary malformations, 45% are more or less restricted to 1 of the 3 areas supplied by the divisions of the fifth cranial nerve (CN). Of facial capillary malformations, 55% involve an area innervated by more than 1 division of the fifth CN, crossing the midline or occurring bilaterally.

Growth

Growth of the capillary malformation is commensurate with that of the child. Capillary malformations remain present for life. Capillary malformations show no tendency toward involution.

Evolution

Capillary malformations may change from pink in infancy to red in early adulthood to deep purple during middle age in some individuals. The surface may become thickened with a cobblestonelike contour. Approximately 65% of facial capillary malformations develop these changes during adulthood.[19]

Nodular vascular lesions may develop, usually in adulthood. Pyogenic granulomas (lobular capillary hemangiomas) with bleeding may develop in capillary malformations, even in childhood.[18]

Associations

Capillary malformation may coexist with other vascular malformations. Geographic (ie, well-circumscribed, sharply bordered) cutaneous lesions carry a much higher probability of associated lymphatic malformations than blotchy stains, especially in patients with Klippel-Trenaunay syndrome.[20]

Physical Examination

Early in life, the lesions appear as flat (macular), mostly well-circumscribed patches. The color varies from pink to red to purple. The color of the capillary malformation does not correlate with the capillary depth or diameter. Blanching with external pressure is variable. In infancy and childhood, the color darkens with crying, fever, or overheating. Capillary malformations are usually unilateral with fairly sharp midline cutoffs. The face is the most frequently affected site, followed by the upper part of the trunk.

Later in life, as the vasculature dilates, the capillary malformation may evolve into a raised, thickened plaque. The capillary malformation becomes deep-red to purple. Lesions may become studded with vascular papules, imparting a cobblestonelike appearance. Vascular papules often form and may be prone to bleeding. Skin and underlying soft tissue or bony hypertrophy may be present. Lobulated capillary hemangiomas (pyogenic granulomas) may form, especially with intraoral lesions.

Associated findings

Ocular and/or CNS involvement occurs in 9.5% of patients with facial capillary malformations. Involvement of V1 distribution seems to be a requirement. The highest incidence appears to be in patients in whom the capillary malformation involves the entire cutaneous distribution of V1, with 78% developing eye or CNS complications.[21]

Glaucoma occurs in approximately 10% of patients with facial capillary malformations, and no leptomeningeal involvement is present. Glaucoma affects 27-45% of patients when capillary malformations involve the skin supplied by both the ophthalmic (CN V1) and the maxillary (CN V2) divisions of the fifth CN, the trigeminal nerve. Glaucoma is less frequent when the face is involved in only 1 of these upper divisions of the trigeminal nerve or if it is affected solely below the eye; however, the prevalence is increased with eyelid involvement. The prevalence may not be correlated with increased vascularity of the choroid or the bulbar conjunctiva. Glaucoma may be due to increased episcleral venous pressure with resultant elevated intraocular pressure, and it can occur without leptomeningeal involvement (eg, in the absence of Sturge-Weber syndrome).

Although difficult to treat, glaucoma associated with periorbital capillary malformations can occur early in childhood; thus, early referral for high-risk patients is important.

Other types of vascular malformations (venous, lymphatic, arterial, or mixed) may be present.

Associated syndromes

Capillary malformation is a cutaneous finding of several syndromes.

Sturge-Weber syndrome

Sturge-Weber syndrome (encephalofacial or encephalotrigeminal angiomatosis) is characterized by the triad of capillary malformations involving the upper facial dermis, the ipsilateral leptomeninges, and the ipsilateral cerebral cortex. It is caused by a somatic activating mutation in the GNAQ gene.[22] Some authorities believe that only 2 features are necessary to make this diagnosis. The facial skin supplied by the ophthalmic branch (CN V1) of the trigeminal nerve must be involved with the capillary malformation for a patient to meet one of the criteria for Sturge-Weber syndrome.

Sturge-Weber syndrome occurs in less than 10% of patients with capillary malformations on the upper eyelid or the forehead. Involvement of areas on the face supplied by only CN V2 or CN V3 does not carry an increased risk for Sturge-Weber syndrome.

No relationship is apparent between the size of the facial capillary malformation and the severity of CNS involvement, and a small percentage of Sturge-Weber syndrome patients lack any cutaneous involvement.[23]

Typically, capillary malformations associated with Sturge-Weber syndrome are more extensive than isolated capillary malformations, and patients often have bilateral facial involvement. Complications include glaucoma, seizures, hemiplegia, mental retardation, cerebral calcifications, subdural hemorrhage, and an increased prevalence of underlying soft tissue hypertrophy. Large variability exists in the severity of associated symptoms.

Klippel-Trenaunay syndrome

Klippel-Trenaunay syndrome (KTS) (angio-osteohypertrophy syndrome) manifests as a triad of capillary malformation, congenital varicose veins, and hypertrophy of underlying tissues, particularly skeletal overgrowth. The sex distribution is equal. The lower limbs are involved in 95% of patients, and involvement is unilateral in 85%. Most patients are asymptomatic at birth, but many experience problems later in childhood. Complications include varicose veins with venous thrombosis and pulmonary embolism; bleeding from varices, the rectum, or the bladder; skin ulceration; increased sweating overlying the capillary malformation; leg circumference or length discrepancy with resultant scoliosis; edema; and recurrent infections.[24] Ultrasonographic measurement of the thigh arterial blood flow may be helpful in predicting future leg length discrepancies in patients with lower extremity capillary malformations.[25]

Parkes-Weber syndrome

With Parkes-Weber syndrome, the diagnostic criteria include an AVM in addition to those listed above for Klippel-Trenaunay syndrome. AVFs are usually diffuse and difficult to ablate. Almost all patients present in childhood with an enlarged, warm extremity. The prognosis is worse than that associated with Klippel-Trenaunay syndrome. A positive bradycardic reaction (Nicoladoni-Branham sign) portends a poorer prognosis. This test is performed by occluding the arterial inflow by compression with a blood pressure cuff. In a limb with a hemodynamically significant AVM, this maneuver leads to reflex bradycardia secondary to a sharp rise in blood pressure. Complications include ulceration and severe lymphedema.

Diffuse capillary malformation with overgrowth

This is a recently proposed designation, which describes patients with an extensive, diffuse, reticulate capillary malformation and variable, but proportionate, hypertrophy without any major complications.[26] A reticulate capillary malformation is defined as networklike, blotchy, nonuniform in color, and without distinct borders. This is in contradistinction to the darker "geographic" stains observed in KTS. These patients do not fit the diagnostic criteria of the other disorders marked by capillary malformations and overgrowth such as KTS or Parkes-Weber syndrome. Patients still require periodic evaluation to monitor for leg length discrepancy. They exhibit normal neurologic development and proportionate overgrowth rather than progressive, disproportionate asymmetry.

Cobb syndrome

In Cobb syndrome (cutaneomeningospinal angiomatosis), a cutaneous vascular lesion in the skin overlying the spine, is associated with vascular malformations (venous or arteriovenous) in the subjacent spinal meninges. Possible complications result from neurologic damage caused by mass effect on the spinal cord or nerves, bone erosion, and subarachnoid hemorrhage.

Wyburn-Mason syndrome

Wyburn-Mason syndrome (unilateral retinocephalic syndrome), also known as Bonnet-Dechaume-Blanc syndrome, manifests as facial capillary malformations associated with unilateral AVM of the retina and the intracranial optic pathway. Physical findings include monocular amblyopia, mild proptosis, and dilatation of conjunctival vessels. Capillary malformations may occur anywhere on the ipsilateral face (not just the eyelids or periorbitally), and they may have associated facial hypertrophy or occasional involvement of the optic chiasm, the hypothalamus, the midbrain, and the basal ganglia, with associated mental retardation or neurologic signs and symptoms.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome

CM-AVM syndrome is an autosomal dominant disorder caused by mutations in RASA1. Multifocal, small, round-to-oval, pinkish-to-red cutaneous capillary malformations are seen in over 90% of individuals with RASA1 mutations and pinpoint red macules with pale halos are seen in about 20% of patients with clinically diagnosed CM-AVM syndrome.[27] At least some of the capillary malformations may actually be cutaneous AVMs or overly subcutaneous AVMs. Hypotrichosis has been described within the capillary malformations, suggesting that hair follicle development may also be affected by the causative mutation.[28] These cutaneous capillary malformations can accompany an internal or cutaneous AVM or arteriovenous fistula (AVF). Intracerebral AVMs or AVFs have been reported in about 7% of patients with CM-AVM syndrome and can be associated cerebral vascular accidents.

PIK3CA-related overgrowth spectrum (PROS)

Several other mosaic disorders, caused by somatic activating mutations in the gene for PIK3CA, present with capillary malformations, in addition to other vascular malformations. PIK3CA is in the PI3K-AKT signaling pathway responsible for cell cycle/apoptosis regulation, metabolism, and angiogenesis. Among the syndromes included in the PROS, the most clinically significant include hemihyperplasia-multiple lipomatosis syndrome (HHML), CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome), and megaloencephaly-capillary malformation (MCAP).[29] MCAP, previously termed macrocephaly-cutis marmorata telangiectatica congenita, is a multisystemic disorder characterized by prenatal and postnatal overgrowth, somatic and cerebral asymmetry, megalencephaly with cortical brain abnormalities, specifically polymicrogyria, cardiac arrhythmias, thickened and doughy-feeling subcutaneous tissue, and syndactyly or polydactyly. It has been proposed that Klippel-Trenaunay syndrome may also result from mutations within this pathway as well, but confirmation is lacking.[30, 31]

Microcephaly-capillary malformation (MIC-CAP)syndrome

MIC-CAP syndrome is an autosomal recessive congenital neurocutaneous disorder severely affecting the central nervous system. It is characterized by marked microcephaly, seizures, psychomotor disability, and multiple cutaneous capillary malformations. Affected individuals have variable dysmorphic facial features and hypoplastic distal phalanges.[32] It is caused by mutations in the STAMBP gene, which encodes the deubiquitinating (DUB) isopeptidase, which plays a role in cell surface receptor‒mediated endocytosis and sorting.

Nevus vascularis mixtus

Nevus vascularis mixtus is the name given when a capillary malformation is paired with nevus anemicus, an example of didymosis or twin spotting.

Associated skeletal or neurologic anomalies

Capillary malformation overlying the lumbar spine may be a marker for an underlying primary skeletal or neurologic anomaly, such as spinal dysraphism, tethered spinal cord, lipomeningocele, or diastematomyelia. The prevalence of underlying defects is increased when multiple abnormalities are present in the lumbar skin. Skin markers include acrochordons (skin tags), an abnormal tuft of hair (fawn's tail), lipomas, an irregular (usually deviated) gluteal cleft, or a dermal sinus tract or sacral dimple that is large or superior to the gluteal fold.

Guggisberg et al found that none of 16 patients with an isolated capillary malformation showed occult spinal dysraphism, whereas 7 of 10 patients with capillary malformations in combination with other lumbar congenital anomalies did have an occult spinal dysraphism.[33] Conversely, Tubbs et al found that 21 (17.5%) of 120 patients with an isolated capillary malformation harbored an occult spinal dysraphism, and they recommended MRI for all patients who present with an isolated lumbar capillary malformation.[34]  This approach is not widely accepted, however.

Associated dermatologic anomalies

Phakomatosis pigmentovascularis

Phakomatosis pigmentovascularis refers to the presence of a capillary malformation with a melanocytic or other type of nevus. The histopathologic findings of a capillary malformation in phakomatosis pigmentovascularis are the same as those for isolated capillary malformations.

Four types of phakomatosis pigmentovascularis are described, as follows:

  • Type I is composed of capillary malformation and nevus pigmentosus et verrucosus or epidermal nevus.

  • Type II is a capillary malformation and dermal melanocytosis with or without nevus anemicus; this is the most common type. It also includes nevus of Ota (oculocutaneous melanosis) and can be associated with Sturge-Weber syndrome and Klippel-Trenaunay syndrome.

  • Type III is a capillary malformation and nevus spilus with or without nevus anemicus.

  • Type IV is a capillary malformation, nevus spilus, and dermal melanocytosis with or without nevus anemicus.

Subdivisions of each type include subtype a for cutaneous involvement only and subtype b for cutaneous and systemic involvement. No systemic involvement is reported for type I.

In 2005, another classification scheme for phakomatosis pigmentovascularis has been proposed by Happle. This includes 3 different distinct categories based on the type of associated lesion: phacomatosis cesioflammea (capillary malformation with bluish gray spots as observed with various lesions of dermal melanocytosis), phacomatosis spilorosea (pale pink telangiectatic capillary malformation associated with a nevus spilus), and phacomatosis cesiomarmorata (cutis marmorata telangiectatica congenita with blue spots). A final category includes others that cannot be included in one of the other 3 variants.[35]

Angiolipomas

Asymptomatic, noninfiltrating angiolipomas may be present underlying a capillary malformation in a small minority of patients. These are mostly found on the trunk and pelvic girdle skin and may be associated with laser-resistant capillary malformations.[36]

Complications

Occasionally capillary malformations are complicated by an overlying eczematous dermatitis. The mechanism for this is unknown but has been compared with stasis dermatitis, given the dilated dermal capillaries in each condition. The dermatitis is responsive to topical steroids or topical calcineurin inhibitors; however, it readily recurs shortly after discontinuation of treatment. Laser ablation of the underlying capillary malformation can treat this dermatitis; however, some capillary malformations can develop dermatitis even after laser ablation of the stain.[37]

 

DDx

Diagnostic Considerations

See the list below:

  • Early infantile hemangiomas: Consider a diagnosis of infantile hemangiomas before the onset of rapid proliferation. Infantile hemangiomas are easily differentiated from capillary malformations by the observation of rapid growth in the hemangiomas.

  • Abortive (telangiectatic) infantile hemangiomas: These usually are flat, pink patches with obvious telangiectases running throughout the lesion. These involute slowly over time, albeit slower than typical infantile hemangiomas.

  • Nevus flammeus neonatorum: Synonyms include salmon patch, stork bite, angel kiss, nevus simplex, nevus flammeus nuchae, medial or midline telangiectatic nevus, medial nevus flammeus, and physiologic capillary malformation. They occur on the midline glabella, the nose, the upper lip, the occipital scalp, or the eyelids. They are usually lighter pink than capillary malformations, with rates of 42% in white neonates and 31% in black neonates. In most cases, the anterior facial lesions lighten or resolve by the time the patient is aged 1-2 years; however, the occipital and lumbar lesions may persist throughout life.

  • Beckwith-Wiedemann syndrome

  • Coats disease: Retinal telangiectasia (usually unilateral) is rarely reported with an ipsilateral facial capillary malformation.

  • Cobb syndrome: See Physical Examination.

  • Parkes-Weber syndrome: See Physical Examination.

  • Phacomatosis pigmentovascularis

  • Roberts syndrome: This is characterized by facial capillary malformation, hypomelia, hypotrichosis, cleft lip, and growth retardation.

  • TAR syndrome: This is characterized by congenital thrombocytopenia, bilateral absence or hypoplasia of the radius, and capillary malformations.

  • Sturge-Weber syndrome: See Physical Examination.

  • von Hippel-Lindau disease

  • Wyburn-Mason syndrome: See Physical Examination.

Differential Diagnoses

 

Workup

Imaging Studies

Imaging studies should be performed if Sturge-Weber syndrome is suspected. MRI with gadolinium enhancement is the optimal diagnostic imaging technique for the screening of Sturge-Weber syndrome.

CT scan or MRI findings may be absent during the first few years, unless intravenous contrast is administered. However, even if intravenous contrast is used, some milder lesions may still not be detected. Positive findings include gyral enhancement, enlargement and enhancement of the ipsilateral choroid plexus, progressive cortical atrophy, and gyral calcification. Accelerated myelination in the involved hemisphere also may be an early diagnostic feature before age 6 months in some infants.

Cerebral angiography can detect parenchymal contrast stasis and abnormal cortical veins.

Debate continues regarding the need for and type of diagnostic imaging for patients who present with an isolated capillary malformation. Some authorities believe that in low-risk lesions such as an isolated capillary malformation, either no imaging or ultrasonography (age < 5 mo) is reasonable. Imaging studies should be performed in all patients who have a capillary malformation and another lumbosacral cutaneous anomaly, because the risk is much higher. Some authors recommend MRI for all children who present with an isolated lumbar capillary malformation.

Other Tests

An ophthalmologic evaluation with tonometry to exclude glaucoma in infants with CN V1 and CN V2 or eyelid involvement should be performed semiannually for the first 3 years of life and annually thereafter.

Histologic Findings

Histologically, the abnormal features are difficult to appreciate in tissue samples obtained from children younger than 10 years. With time, the affected vessels become progressively more ectatic and filled with erythrocytes. The ectasia appears to progress from the superficial dermis to the deeper dermis and subcutaneous tissues. The endothelial cells of a capillary malformation do not stain for GLUT-1, a specific marker for infantile hemangiomas.

See the image below.

Histopathologic features of a capillary malformati Histopathologic features of a capillary malformation (nevus flammeus) showing telangiectatic vessels lined by mature-appearing endothelial cells.
 

Treatment

Medical Care

Affected areas can be tattooed with a skin-colored pigment; however, this is not routinely performed.

Use of a cosmetic cover-up is an alternative. Opaque makeup, sold commercially without a prescription under brand names like Dermablend and Covermark, disguises capillary malformations but does not treat them.

At least one report describes partial clearing of a capillary malformation on the arm of a 59-year-old woman after the use of topical imiquimod under plastic wrap occlusion 5 times per week for 4 weeks. The authors attribute the response to antiangiogenic properties of imiquimod through the induction of tissue inhibitor of matrix metalloproteinase-1, an inhibitor of vascular tumor growth.[38] A prospective, controlled trial demonstrated that imiquimod application 3 times weekly for 8 weeks after pulsed-dye laser (PDL) therapy resulted in measurable objective improvement in lightening of the stain than PDL therapy followed by placebo.[39]

Surgical Care

Flashlamp-pumped pulsed-dye laser (PDL) surgery is the treatment of choice for capillary malformations.[40, 41, 42] It uses selective photothermolysis with ultrashort pulses of monochromatic yellow light (585-600 nm), which are preferentially absorbed by oxyhemoglobin in the abnormally dilated superficial dermal blood vessels. Flashlamp-pumped PDL causes selective destruction of these superficial target blood vessels, inducing intravascular coagulation and rupture of some smaller vessels, which later become absorbed and replaced by collagen. The ultrashort laser pulses are shorter than the thermal relaxation time of the vessels, thereby limiting adjacent dermal and epidermal heating and preventing subsequent damage. Kono et al published a thorough review of PDL therapy for capillary malformations,[43] which examines many of the idiosyncrasies of this treatment modality.

Despite few, high quality, randomized-controlled trials comparing the efficacy amongst various laser or light sources, PDL has proven to be effective for clinically relevant clearance of capillary malformations. A Cochrane review demonstrated overall greater than 25% reduction in redness after 1-3 treatments in over half of all subjects treated in these studies.[40]

Skin treated with a PDL immediately develops edema and purpura, the latter of which generally last 1-2 weeks. PDL surgery is repeated between 2 weeks and 3 months. Preliminary findings suggest that a 2-week interval between treatments is as safe and effective as a 3-month interval. The shorter interval serves to increase the treatments in early infancy, potentially avoiding general anesthesia later in childhood.[44] Flashlamp-pumped PDL is relatively safe; major risks include pigmentation alterations (hyperpigmentation, which is always transient, and potentially permanent hypopigmentation), crusting, and, rarely, scarring. Immediate adverse events associated with PDL therapy are pain (a hot snapping sensation that can increase with repeated pulses) and combustion (especially of hair-bearing areas and in the presence of increased ambient oxygen). PDL therapy can be performed on patients with skin types V and VI, but with a potentially higher risk of pigmentary complications.

Decreasing the time between treatments increases the number of treatments that can be delivered prior to age 6 months, thereby reducing the number of subsequent treatments needed under general anesthesia. The safety and efficacy of more frequent PDL treatments of capillary malformations in infancy was investigated in pilot, prospective, patient-controlled study of 10 patients. The entire capillary malformation was treated initially using a 595-nm (Vbeam) PDL, and then half the capillary malformation was randomly selected for 2-week interval PDL treatment and half to 3-month intervals for two additional PDL treatments. An independent, blinded dermatologist evaluated photographs of the capillary malformations taken 3 months after treatment. Nine infants finished the study. More improvement on the 2-week interval treated side was seen in 3 infants (33%), and more improvement was seen on the 3-month interval treated side in four infants (44%). No difference in the two sides was noted in two infants (22%). Treatments were well tolerated, with no complications reported. The study results suggest that 2-week interval PDL treatments of capillary malformations in infants younger than 6 months is effective and well tolerated, without adverse effects. The preliminary data suggested possible superior efficacy with the 3-month interval treatment; however, larger studies are warranted for stronger evidence. More frequent treatment of capillary malformations without general anesthesia should be investigated further to decrease the risk of repeated exposure to general anesthesia in young children.

Some authorities advocate treatment beginning as early as 7-14 days of life, yet the age at which laser treatment achieves maximal response is unknown. Some studies indicate a better response if treatment is commenced before the patient is aged 1 year, while others reveal no difference. From a psychosocial perspective, treatment commencing in infancy is most beneficial.

The response rate depends on several variables. The first is anatomical location, with rates in descending order of location from best to worst as follows: neck, torso, face, and hand and arm; and with rates in descending order of location from best to worst for facial capillary malformations as follows: forehead, lateral part of the face, temple, and central part of the face. The second variable is size; smaller lesions appear to have higher response rates. These variables are influenced by the histologic features of capillary malformations. In 2004, videodermoscopy was used to demonstrate that capillary malformations with smaller vessels deep in the dermis were the most difficult to eradicate with PDL.[45]

Investigations are ongoing to explore methods to improve the outcome of laser surgery, including adjunctive use of exogenous heat,[46] the topical application of the angiogenesis inhibitors rapamycin[47] or imiquimod[48] postoperatively, or intravenous porphyrin derivatives (photodynamic therapy)[49] prior to laser surgery. While the early observations are promising, these interventions are strictly experimental at this time.

See the images below.

Capillary malformation on the left preauricular as Capillary malformation on the left preauricular aspect of the cheek, the ear, and the neck in a neonate (same patient as in Media Files 3-4).
Same patient as in Media Files 2 and 4 immediately Same patient as in Media Files 2 and 4 immediately after test spots with the pulsed-dye laser at 585 nm. Note the purpuric macules where the laser impacted in a linear distribution on the preauricular aspect of the cheek.
Same patient as in Media Files 2-3 after 4 treatme Same patient as in Media Files 2-3 after 4 treatments with the pulsed-dye laser. Treatments were given at 2-month intervals in an outpatient setting using topical anesthetic.

Redarkening of capillary malformations can occur in patients treated by laser.[50] The exact percentage of patients in which this occurs is unknown, with estimates from 11-50%. Currently, no characteristics help predict which lesions will redarken. No capillary malformations darken to the degree they were prior to embarking on laser treatment. Fifty-nine percent of patients are satisfied with the overall treatment result.[51]

Earlier laser therapies that caused an unacceptably high rate of scarring are not recommended; these therapies include carbon dioxide laser, copper vapor laser, and argon laser. Other modalities, such as intense pulsed light devices,[52] alexandrite laser,[53] and the long-pulse[54] or frequency-doubled Nd:YAG laser,[55] are reported to be effective in certain instances, but they are generally considered to have higher complication rates than the PDL.

Previous nonlaser treatments determined unreliable or deleterious include surgical excision, radium implants, cryosurgery, electrocautery, sclerotherapy, and grenz ray radiotherapy.

Innovative methods such as laser speckle imaging[56] and photoacoustic imaging[57] to more accurately assess the vessel density, depth, and diameter and immediate efficacy of laser surgery are ongoing and represent the next frontiers toward improved treatment outcomes.

Consultations

Consult a pediatric dermatologist, a general dermatologist, or a specialist at a laser center or a vascular lesion center for evaluation and early intervention if indicated.

Consult an ophthalmologist for tonometry to exclude glaucoma in infants with CN V1 and CN V2 or eyelid involvement. An ophthalmologist can also evaluate for evidence of ocular capillary malformation in patients with Sturge-Weber syndrome.

Consult a radiologist or refer the patient to a vascular lesion center if underlying complicating vascular, neural, or skeletal malformations are suspected. If a leg-length discrepancy is apparent in a patient with a lower extremity capillary malformation, consult a pediatric orthopedic surgeon.

Consult a neurologist if Sturge-Weber syndrome is suspected.