Residency · Residency · Dermatology

Vascular Malformations in Children

Introduction

Vascular malformations are structural anomalies of blood vessels that arise from errors in vascular morphogenesis. Unlike infantile hemangiomas, vascular malformations are present at birth, grow commensurately with the child, never involute spontaneously, and are GLUT-1 negative. The ISSVA (International Society for the Study of Vascular Anomalies) classification system provides the framework for categorizing these lesions by flow characteristics and vessel type.

ISSVA Classification

Vascular malformations are divided into low-flow malformations, which include capillary (CM), venous (VM), lymphatic (LM), and combined forms, and high-flow malformations, which include arteriovenous malformations (AVM) and arteriovenous fistulae (AVF). Combined malformations involve multiple vessel types (CVM, CLM, CLVM, CAVM, and others). Malformations are further subclassified as simple (single vessel type), combined (multiple vessel types), or those associated with overgrowth syndromes.

Capillary Malformations

Port-Wine Stain (Nevus Flammeus)

Port-wine stains are present at birth as flat, pink-to-red patches that become progressively darker (violaceous) over decades and may develop nodular hypertrophy. Approximately 90% are caused by somatic activating mutations in GNAQ (R183Q). They do not blanch completely with pressure and grow proportionally with the child. When a facial CM involves the V1 distribution, evaluation for Sturge-Weber syndrome (SWS) is warranted, as this syndrome involves leptomeningeal and ocular (glaucoma) vascular malformations. Treatment with pulsed dye laser (PDL) at 585 to 595 nm is first-line, with earlier treatment in infancy yielding better results, though multiple sessions are required. Recurrence and resistance to PDL are common, and newer approaches include combination with topical rapamycin or anti-angiogenic agents.

Other Capillary Malformations

Salmon patch (nevus simplex) is a midline CM found on the forehead, glabella, eyelids, or nape of the neck, referred to as an "angel's kiss" or "stork bite," and fades spontaneously in most cases. Cutis marmorata telangiectatica congenita (CMTC) presents as a reticulated vascular network with phlebectasia and may be associated with limb asymmetry. CM-AVM syndrome features multifocal small CMs with a surrounding pale halo, caused by RASA1 or EPHB4 mutations, and requires evaluation for associated AVMs.

<image>Clinical photographs comparing a salmon patch (nevus simplex) on the glabella of a newborn with a port-wine stain capillary malformation on the lateral face showing progressive darkening from infancy to adulthood</image>

Venous Malformations

Venous malformations are the most common symptomatic vascular malformation and present as soft, compressible, blue-purple masses that enlarge with Valsalva maneuver or dependent positioning. Somatic activating mutations in the TEK (TIE2) gene have been identified in sporadic VM, while glomuvenous malformations harbor germline glomulin (GLMN) mutations. Phleboliths on imaging are pathognomonic. Venous malformations may cause pain from localized intravascular coagulopathy (LIC), characterized by elevated D-dimer and low fibrinogen, which is distinct from disseminated intravascular coagulation. MRI is the imaging modality of choice, showing T2-weighted hyperintensity with gadolinium enhancement and no flow voids. Treatment options include compression garments, sclerotherapy (sodium tetradecyl sulfate, polidocanol, ethanol), surgical resection, and sirolimus for extensive or refractory lesions. Low-dose aspirin or low-molecular-weight heparin may be used for symptomatic LIC.

Lymphatic Malformations

Previously termed "cystic hygromas" or "lymphangiomas," lymphatic malformations are classified as macrocystic, microcystic, or mixed. Most are located in the head and neck (75%) and axillae. They present as soft, transilluminant masses (macrocystic) or firm, non-transilluminant masses (microcystic). Acute enlargement may occur with upper respiratory infections or intralesional hemorrhage. Macrocystic lesions respond well to sclerotherapy using OK-432 (picibanil), doxycycline, or bleomycin, while microcystic lesions are more recalcitrant. Sirolimus has shown efficacy in complex, diffuse lymphatic malformations. Surgical excision is considered for localized, resectable lesions but carries high recurrence rates for infiltrative disease.

Arteriovenous Malformations

Arteriovenous malformations are high-flow lesions composed of abnormal connections between arteries and veins without an intervening capillary bed, forming a central nidus. They are present at birth but may not become clinically apparent until puberty, trauma, or hormonal changes trigger expansion. The Schobinger staging system describes their progression: Stage I (quiescent, with a warm pink patch and AV shunting on Doppler), Stage II (expansion, with pulsation, thrill, and bruit), Stage III (destruction, with pain, ulceration, bleeding, and dystrophic skin changes), and Stage IV (decompensation, with high-output cardiac failure). Somatic MAP2K1 mutations have been identified in some sporadic AVMs. MRI with MR angiography shows flow voids and enlarged feeding and draining vessels, while conventional angiography is used for treatment planning. Treatment involves embolization followed by surgical resection within 24 to 48 hours, as embolization alone often leads to recurrence through collateral recruitment. It is critical to never ligate feeding vessels, as this eliminates future embolization access and promotes collateral development.

<image>MRI and clinical image comparison showing a venous malformation (T2-bright, compressible blue mass) versus an arteriovenous malformation (flow voids on MRI, warm pulsatile mass with overlying skin changes)</image>

Vascular Malformation Syndromes

Sturge-Weber Syndrome

Sturge-Weber syndrome involves a capillary malformation in the V1 distribution with ipsilateral leptomeningeal and choroidal vascular malformations, caused by a somatic GNAQ mutation (the same as isolated port-wine stains). Complications include glaucoma (30 to 70%), seizures, hemiparesis, and intellectual disability. Management includes ophthalmologic screening, neuroimaging with contrast-enhanced MRI, antiepileptic medications, and PDL for the cutaneous CM.

Klippel-Trenaunay Syndrome (KTS)

Klippel-Trenaunay syndrome is defined by the triad of a capillary malformation, venous and/or lymphatic malformation, and soft tissue or bony overgrowth of an extremity. It is caused by somatic PIK3CA mutations and falls within the PIK3CA-related overgrowth spectrum (PROS). Complications include chronic pain, LIC and thrombosis, limb length discrepancy, and cellulitis. Alpelisib, a PIK3CA inhibitor, has been approved for PROS conditions.

Parkes Weber Syndrome

Parkes Weber syndrome features a CM with arteriovenous fistulae and limb overgrowth. It is distinguished from KTS by its high-flow component and is associated with RASA1 mutations.

<image>Diagram illustrating key vascular malformation syndromes: Sturge-Weber with V1 port-wine stain and brain MRI showing leptomeningeal enhancement, Klippel-Trenaunay with limb CM and overgrowth, and Parkes Weber with AV shunting on Doppler</image>

Key Clinical Pearls

Vascular malformations never involute. If a lesion appears to be shrinking, the diagnosis should be reconsidered, as it is likely a vascular tumor rather than a malformation. D-dimer elevation in a patient with a vascular anomaly suggests venous malformation with localized intravascular coagulopathy, not DIC. Port-wine stains in V1 warrant MRI of the brain and ophthalmologic evaluation for Sturge-Weber syndrome. Clinicians should always assess for underlying genetic syndromes (GNAQ, PIK3CA, RASA1, TEK) as targeted therapies are emerging. Sirolimus (mTOR inhibitor) has become a cornerstone for complex, low-flow vascular malformations refractory to conventional management.

References

1. Wassef M, Blei F, Adams D, et al. Vascular anomalies classification: recommendations from the International Society for the Study of Vascular Anomalies. Pediatrics. 2015;136(2):e203-e214.
2. Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):1971-1979.
3. Adams DM, Trenor CC, Hammill AM, et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics. 2016;137(2):e20153257.
4. Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Pharmacodynamic study of miransertib in individuals with Proteus syndrome. Am J Hum Genet. 2019;104(3):484-491.

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