Vascular lesions in the newborn

INTRODUCTION — Vascular lesions, including vascular neoplasms and vascular malformations, are common in newborns [1]. Although the majority of these lesions are benign and self-limited conditions, some may be part of complex syndromes or systemic disorders or may be associated with complications.

Vascular lesions presenting in the newborn will be reviewed here. Other neonatal skin lesions and inherited skin disorders are discussed separately.

●(See "Vesicular, pustular, and bullous lesions in the newborn and infant".)

●(See "Skin nodules in newborns and infants".)

●(See "Skin lesions in the newborn and infant".)

●(See "Congenital melanocytic nevi".)

●(See "The genodermatoses: An overview".)

CLASSIFICATION OF VASCULAR ANOMALIES — The 2018 classification of the International Society for the Study of Vascular Anomalies divides the vascular anomalies into the following broad categories [2]:

●Vascular tumors, including benign, borderline, and malignant tumors

●Simple malformations, including capillary malformations, lymphatic malformations, venous malformations, and arteriovenous fistula

●Combined vascular malformations, defined as two or more vascular malformations found in a single lesion

●Anomalies of major named vessels

●Vascular malformations associated with other anomalies, which include Sturge-Weber syndrome, Klippel-Trenaunay syndrome, macrocephaly-capillary malformation, Proteus syndrome, and CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies/scoliosis) syndrome

VASCULAR TUMORS

Infantile hemangiomas — Infantile hemangiomas are the most common benign tumors of infancy. The pathophysiology, clinical features, complications, evaluation, and management of infantile hemangiomas are discussed in detail separately. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Infantile hemangiomas: Evaluation and diagnosis" and "Infantile hemangiomas: Management".)

Congenital hemangiomas — Congenital hemangiomas are rare, benign vascular tumors that are present and fully grown at birth. They present as bossed plaques (picture 1) or exophytic masses (picture 2) located on the head, neck, or limbs. Based upon their natural history, two major subtypes have been recognized: rapidly involuting congenital hemangiomas (RICH) and noninvoluting congenital hemangiomas (NICH). There is also a partially involuting congenital hemangioma (PICH) that shares overlapping features seen in a RICH and NICH.

Congenital hemangiomas are reviewed separately. (See "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)".)

Tufted angioma and kaposiform hemangioendothelioma — Tufted angioma and kaposiform hemangioendothelioma (KHE) are rare vascular tumors that typically present during infancy or early childhood. They may be associated with the Kasabach-Merritt phenomenon, a life-threatening complication characterized by severe thrombocytopenia and coagulopathy.

Tufted angioma, KHE, and the Kasabach-Merritt phenomenon are discussed in detail separately. (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)

Pyogenic granuloma — Pyogenic granuloma or lobular capillary hemangioma is a benign vascular tumor of the skin or mucous membranes characterized by rapid growth and friable surface (picture 3). Although more common in infants older than four months and young children, pyogenic granuloma may occur in the newborn [3,4].

The pathogenesis, clinical manifestations, diagnosis, and treatment of pyogenic granuloma are discussed separately. (See "Pyogenic granuloma (lobular capillary hemangioma)".)

VASCULAR MALFORMATIONS — Vascular malformations are anomalies of vessel morphogenesis. Unlike neoplasms, endothelial turnover is normal. Depending upon the type of involved vessels and flow characteristics, vascular malformation can be divided into low flow (capillary, venous, lymphatic, or combination) and high flow (arterial, arteriovenous).

Vascular malformations are always present at birth but often are clinically subtle and become more apparent over time as they slowly expand in proportion to the infant's overall growth. In addition, there is progressive ectasia secondary to changes in blood or lymphatic flow, pressure associated with trauma, or hormonal changes such as at puberty. Vascular malformations are in most cases an isolated finding but may occur in the setting of complex inherited and congenital disorders.

Capillary malformations — Capillary malformations appear as pink-red macular lesions on the skin or mucosa. They are present at birth and generally persist throughout life, although some variants, such as nevus simplex, may fade and disappear during the first few years of life. Capillary malformations may be an isolated finding or occur in association with a wide range of cutaneous or systemic abnormalities in complex inherited or sporadic disorders. (See 'Vascular malformations associated with other anomalies' below and "Capillary malformations (port wine birthmarks) and associated syndromes".)

Nevus simplex (macular stain) — Nevus simplex (also called macular stain, salmon patch, stork bite, or angel kiss) presents as single or multiple blanchable, pink-red patches in newborn infants (picture 4A-C). These lesions occur in 40 to 60 percent of infants, most commonly on the eyelid, glabella, and midline of the nape of the neck. Less common sites of involvement include the scalp, nose, lip, and back [5]. Nevus simplex generally fades within one to two years, although lesions on the back of the neck may persist unchanged with little consequence [6].

Rarely, nevus simplex may be associated with extracutaneous disorders such as spinal dysraphism, Beckwith-Wiedemann syndrome, macrocephaly-capillary malformation syndrome, or other conditions [5]. (See "Beckwith-Wiedemann syndrome" and 'Cutis marmorata telangiectatica congenita' below.)

In patients with lumbosacral nevus simplex, imaging studies to evaluate for underlying spinal dysraphism are recommended when another lumbosacral abnormality such as a dermal sinus or pit, lipoma, patch of hypertrichosis, or deviated gluteal cleft is present [5]. It is unclear whether spinal imaging should be routinely performed in patients with isolated lumbosacral nevus simplex as the risk of underlying spinal abnormalities may be low in this group [7-10]. We typically do not image patients in the absence of other lumbosacral abnormalities. (See "Closed spinal dysraphism: Pathogenesis and types".)

Port wine birthmarks — Port wine birthmarks or nevus flammeus are low-flow vascular malformations of dermal capillaries and postcapillary venules. They are present at birth in 0.1 to 0.2 percent of newborns as blanchable pink to red patches on skin and/or mucosa and may be located anywhere on the body, typically with a unilateral or segmental distribution that respects the midline (picture 5A-C) [1]. Port wine birthmarks do not regress but grow in proportion to the child's growth and become thicker and darker in color during adulthood. Port wine birthmarks and associated syndromes are discussed separately. (See "Capillary malformations (port wine birthmarks) and associated syndromes".)

Lymphatic malformations — Lymphatic malformations (LM) are benign, slow-flow vascular lesions composed of dilated lymphatic channels or cysts lined by endothelial cells with a lymphatic phenotype [2]. They are classified as macrocystic (cystic hygroma), microcystic (lymphangioma circumscriptum), and mixed type.

Macrocystic lymphatic malformation (cystic hygroma) — Macrocystic lymphatic malformation, also referred to as cystic hygroma, is composed of collections of large, interconnected lymphatic cysts lined by a thin endothelium. It presents at birth as a large, poorly delimitated, translucent, soft mass covered by normal skin, most commonly located in the cervicofacial region, axilla, or lateral chest wall (picture 6). Cystic hygroma can be detected prenatally in the first trimester of pregnancy and, in approximately 50 percent cases, is associated with chromosomal abnormalities, such as Down syndrome, Turner syndrome, and Noonan syndrome. (See "Enlarged nuchal translucency and cystic hygroma".)

Microcystic lymphatic malformation (lymphangioma circumscriptum) — Lymphangioma circumscriptum is a type of microcystic lymphatic malformation that may be present at birth or appear in the first few years of life. The most frequent localizations are proximal extremities, trunk, axilla, and the oral cavity. Clinically, lymphangioma circumscriptum presents as a cluster of clear, translucent or hemorrhagic vesicles that may intermittently leak lymphatic fluid (picture 7). (See "Soft tissue lesions of the oral cavity in children", section on 'Lymphangiomas'.)

Venous malformations — Venous malformations are the most frequent low-flow vascular malformations [11]. They may involve the skin, mucosa, deep soft tissues, and internal organs. They result from inborn errors in the development of the venous network, leading to dilated and dysfunctional veins that are deficient in smooth muscle cells. Although inherited forms exist, more than 90 percent of venous malformations occur sporadically.

In the newborn, mucocutaneous venous malformations present as bluish, ill-defined, compressible lesions (picture 8). A thrill or bruit is absent on auscultation, and, on palpation, the involved skin is not warmer than the adjacent skin. Patients with extensive venous malformations develop a chronic localized intravascular coagulopathy with permanently elevated D-dimer levels that may result in thrombosis or bleeding [12].

The pathogenesis, clinical presentation, diagnosis, and management of venous malformations are discussed separately. (See "Venous malformations".)

Arteriovenous malformations — Arteriovenous malformations are fast-flow vascular malformations composed of abnormal arteries, veins, and capillaries, with direct arteriovenous communications resulting in arteriovenous shunting [2]. They may occur sporadically or in patients with hereditary hemorrhagic telangiectasia or capillary malformation-arteriovenous malformation.

In the newborn, arteriovenous malformations present as capillary malformation-like lesions (picture 9) or, less frequently, as purple-red swollen lesions (picture 10). Lesions are warm on palpation and may have an audible thrill or bruit. (See 'Capillary malformation-arteriovenous malformation syndrome' below.)

VASCULAR MALFORMATIONS ASSOCIATED WITH OTHER ANOMALIES

Sturge-Weber syndrome — Sturge-Weber syndrome is a rare congenital, but not hereditary, vascular disorder characterized by a facial capillary malformation involving the V1 +/- V2 dermatome and an associated leptomeningeal vascular malformation (picture 11A-B). These malformations may be associated with specific ocular (predominantly glaucoma) and neurologic abnormalities, including seizures, hemiparesis, intellectual disability, and behavior problems. Sturge-Weber syndrome is discussed in detail separately. (See "Sturge-Weber syndrome".)

Klippel-Trenaunay syndrome — Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the presence of capillary malformation, venous malformation or varicosities, and limb overgrowth, with or without lymphatic anomalies (picture 12) [2]. KTS is considered part of the PIK3CA-related overgrowth spectrum (PROS) [13]. The pathogenesis, clinical manifestations, diagnosis, and management of KTS are discussed in detail separately. (See "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management".)

Cutis marmorata telangiectatica congenita — Cutis marmorata telangiectatica congenita (CMTC; also called nevus vascularis reticularis and congenital livedo reticularis) is a vascular anomaly characterized by a generalized or localized reticulated cutaneous vascular network. No sex predominance has consistently been demonstrated [14,15].

Generalized CMTC can be a feature of Adams-Oliver syndrome (MIM #100300), a rare developmental disorder characterized by aplasia cuts congenita and limb defects. In a review of 78 patients with CMTC, CMTC was generalized in 17 patients (22 percent), and 15 of these (88 percent) met the criteria for the diagnosis of Adams-Oliver syndrome [16]. (See "Aplasia cutis congenita", section on 'Associated genetic syndromes or congenital anomalies'.)

Like cutis marmorata (picture 13), it may be accentuated by cold. However, unlike cutis marmorata, the cutaneous abnormalities do not usually resolve with rewarming and exhibit a coarser vasculature that may be associated with skin atrophy and ulceration (picture 14A-B). (See "Skin lesions in the newborn and infant", section on 'Cutis marmorata'.)

In more than two-thirds of cases, CMTC affects the limbs (especially the legs), which may become discrepant in size and shape in approximately half of the cases [14,17]. The face and trunk are less commonly affected. Lesions are unilateral in 65 percent of cases [14]. They usually fade or resolve spontaneously within two years but rarely may persist unchanged [15,18].

If limb length discrepancy is noted, standing leg-length radiographs are recommended at the age of 10 years for girls or 12 years for boys; if limb length discrepancy is >2 cm, orthopedic referral may be warranted [17]. Other cutaneous and extracutaneous features associated with CMTC include port wine birthmark, glaucoma (especially with facial involvement), localized aplasia cutis congenita, cleft palate, or other malformations [15,16,19-21].

Capillary malformation-arteriovenous malformation syndrome — Capillary malformation-arteriovenous malformation syndrome (CM-AVM, MIM #608354) is an autosomal dominant disorder caused by mutations in the RASA1 gene [22]. CM-AVM presents with multiple small capillary malformations associated with high-flow arteriovenous malformations and arteriovenous fistulas located in the soft tissues, bone, or central nervous system. Red punctate spots surrounded by pale halos, often with associated hypotrichosis, are frequent findings [23]. (See "Capillary malformations (port wine birthmarks) and associated syndromes", section on 'Capillary malformation-arteriovenous malformation syndrome'.)

Macrocephaly-capillary malformation syndrome — Macrocephaly-capillary malformation (M-CM) syndrome, previously named macrocephaly-cutis marmorata telangiectatica congenita (MIM #602501), is a genetic syndrome characterized by an enlarged head circumference and patchy, reticular capillary malformations that sometimes resemble CMTC, but with a finer, livedo-like pattern and no atrophy [24-26]. Other clinical features may include polydactyly/syndactyly, neonatal hypotonia, developmental delay, and structural brain abnormalities [24,27,28]. The vascular lesions often fade during the first few years of life. (See "Capillary malformations (port wine birthmarks) and associated syndromes", section on 'Microcephaly-capillary malformation syndrome'.)

Phakomatosis pigmentovascularis — Phakomatosis pigmentovascularis (PPV) is a rare syndrome characterized by the association of a capillary malformation with dermal melanocytosis (Mongolian spot, nevus of Ota), nevus spilus, or epidermal nevus. The etiology is thought to be a developmental abnormality of the vasomotor nerves and melanocytes, both derived from neural crest [29]. All ethnic groups may be affected [30]. Five types of PPV have been identified (table 1), the most common being type II or phakomatosis cesioflammea (port wine birthmark plus blue spots such as nevus of Ota or Mongolian spots), formerly known as PPV types IIa and IIb [31,32]. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Dermal melanocytoses' and "Epidermal nevus and epidermal nevus syndrome".)

Capillary malformation is present in most PPV types and is usually extensive. In one series of 15 PPV cases, all had facial capillary malformations, and 80 percent had additional capillary malformations in other areas [31]. As many as half of patients have other associated cutaneous lesions, most commonly nevus anemicus and café-au-lait spots [31].

It has been estimated that approximately 50 percent of patients have systemic involvement; neurologic, ocular, and skeletal abnormalities occur most frequently [31,33]. Neurologic abnormalities usually present in the first few months of life and include psychomotor retardation, seizures, intracranial calcifications, or cerebral atrophy [34]. Ocular involvement, such as blue-gray scleral discoloration, is also common. Management and outcome depend upon the presence of other associated conditions.

Proteus syndrome — Proteus syndrome is an extremely rare disorder caused by somatic activating mutations in the AKT1 oncogene and characterized by asymmetric and disproportionate progressive overgrowth of body parts (picture 15) [35]. Cutaneous findings are present in approximately 40 percent of neonates and include capillary, lymphatic, or venous malformations; epidermal nevi; connective tissue nevi; lipomas; and café au lait macules. The vascular malformations are usually extensive, covering a large portion of the body, and may be associated with visceral vascular malformations. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome", section on 'Proteus-like syndrome'.)

CLOVES syndrome — CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies/scoliosis) syndrome (MIM #6129180) is a rare disorder caused by somatic mosaicism for postzygotic activating mutations in the PIK3CA gene on chromosome 3q26 [36]. The term PIK3CA-related overgrowth spectrum (PROS) is used to encompass multiple clinical syndromes with segmental tissue and/or vascular overgrowth associated with somatic PIK3CA mutations, including CLOVES, M-CM syndrome, fibroadipose overgrowth, and KTS [37,38]. (See "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management", section on 'CLOVES syndrome'.)

Patients with CLOVES syndrome present at birth with truncal, lipomatous masses of various sizes infiltrating the adjacent tissues; combined vascular malformations, including capillary, lymphatic, venous (phlebectasias), and arteriovenous malformations (geographic stains); hand and feet deformities (macrodactyly, "sandal gap" toe deformity); and scoliosis [39]. In contrast with Proteus syndrome, the overgrowth present at birth is nonprogressive.

Patients with CLOVES syndrome have an increased risk of developing Wilms tumor (WT). In a review of 122 patients with CLOVES syndrome, 4 (3.3 percent) developed WT by the age of two years [40]. This incidence was significantly higher than that observed in the general population (1 in 10,000 births).

Maffucci syndrome — Maffucci syndrome is a rare developmental disorder characterized by venous vascular malformations that may be present at birth and multiple enchondromas in early childhood [41]. Maffucci syndrome is caused by somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 and is associated with a substantial risk of malignant transformation of enchondroma to chondrosarcoma later in life [42]. (See "Venous malformations", section on 'Maffucci syndrome'.)

OTHER VASCULAR LESIONS

Nevus anemicus — Nevus anemicus is a vascular anomaly presenting at birth as a pale area of the skin of various size and shape, usually located on the trunk (picture 16). It is caused by a localized, increased vascular sensitivity to endogenous catecholamines resulting in persistent vasoconstriction. On diascopy, which consists in applying pressure to the lesion and adjacent normal skin with a glass slide, nevus anemicus is indistinguishable from the surrounding skin.

Nevus anemicus is in most cases an isolated finding but may occur in association with several genetic syndromes, including phakomatosis pigmentovascularis, neurofibromatosis, and tuberous sclerosis complex [43-46]. (See 'Phakomatosis pigmentovascularis' above and "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis" and "Tuberous sclerosis complex: Clinical features".)

STING-associated vasculopathy with onset in infancy — Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI; MIM #615934) is an autoinflammatory disease caused by gain-of-function heterozygous mutations in the gene encoding STING (TMEM173, transmembrane protein 173, on chromosome 5q31.2), resulting in the upregulation of type 1 interferon signaling and elevated levels of interferon-induced cytokines in the peripheral blood [47]. Patients presents in early infancy with a hyperinflammatory state, severe cutaneous vasculopathy, and interstitial lung disease. (See "Autoinflammatory diseases mediated by interferon production and signaling (interferonopathies)", section on 'STING-associated vasculopathy with onset in infancy (SAVI)'.)

Cutaneous lesions include purple-red telangiectatic plaques, pustules, and blisters involving the cheeks, helix and lobule of the ears, tip of the nose, and dorsal side of the hands, fingers, and toes [47,48]. These lesions worsen with cold weather and may ulcerate, leading to tissue loss and severe scarring. Skin biopsy reveals microthrombotic vascular changes and a dense pericapillary lymphocytic and neutrophilic infiltrate with nuclear dust.

SUMMARY AND RECOMMENDATIONS

●Classification – Vascular lesions are common in newborns. They are classified into vascular tumors, simple malformations, combined malformations, anomalies of major named vessels, and malformations associated with other anomalies. (See 'Classification of vascular anomalies' above.)

●Vascular tumors – Infantile hemangiomas are the most common benign tumors of infancy. Rare vascular tumors of the newborn include congenital hemangioma, tufted angioma and kaposiform hemangioendothelioma, and pyogenic granuloma. These tumors are discussed in detail separately. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)" and "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)

●Vascular malformations – Vascular malformations are anomalies of vessel morphogenesis. Depending upon the type of involved vessels and flow characteristics, vascular malformation can be divided into low flow (capillary, venous, lymphatic, or combination) and high flow (arterial, arteriovenous). They may occur in isolation or in the setting of complex inherited and congenital disorders. (See 'Vascular malformations' above.)

•Capillary malformations appear as pink-red macular lesions on the skin or mucosa (picture 17). They are present at birth and generally persist throughout life, although some variants, such as nevus simplex, may fade and disappear during the first few years of life. Capillary malformations may be an isolated finding or occur in association with other cutaneous or systemic abnormalities in complex inherited or sporadic disorders. (See 'Capillary malformations' above and "Capillary malformations (port wine birthmarks) and associated syndromes".)

•Lymphatic malformations (LM) are benign, slow-flow vascular lesions composed of dilated lymphatic channels or cysts lined by endothelial cells with a lymphatic phenotype. They are classified as macrocystic (cystic hygroma) (picture 6), microcystic (lymphangioma circumscriptum) (picture 7), and mixed type. (See 'Lymphatic malformations' above.)

•Venous malformations are low-flow vascular malformations presenting as bluish, ill-defined, compressible nodules or masses (picture 8). They may involve the skin, mucosa, deep soft tissues, and internal organs. Large lesions may develop a chronic localized intravascular coagulopathy that results in thrombosis or bleeding. Venous malformations are discussed in detail separately. (See "Venous malformations".)

•Arteriovenous malformations are composed of abnormal arteries, veins, and capillaries, with direct arteriovenous communications resulting in arteriovenous shunting. The may present clinically as capillary malformation-like lesions (picture 9) or purple-red, warm, painful lesions that may become ulcerated and bleed (picture 10).

●Vascular malformations associated with other anomalies – Vascular malformations associated with other anomalies include Sturge-Weber syndrome, Klippel-Trenaunay syndrome, macrocephaly-capillary malformation, Proteus syndrome, and CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies/scoliosis) syndrome. (See 'Vascular malformations associated with other anomalies' above.)

●Nevus anemicus – Nevus anemicus is a vascular anomaly presenting at birth as a pale area of the skin of various size and shape, usually located on the trunk (picture 16). It is caused by a localized increased vascular sensitivity to endogenous catecholamines resulting in persistent vasoconstriction. Nevus anemicus is in most cases an isolated finding but may occur in association with phakomatosis pigmentovascularis, neurofibromatosis, or tuberous sclerosis complex. (See 'Nevus anemicus' above.)

●STING-associated vasculopathy with onset in infancy – STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease presenting in early infancy with a hyperinflammatory state, severe cutaneous vasculopathy, and interstitial lung disease. Vascular lesions include telangiectatic plaques, pustules, and blisters involving the cheeks, ears, tip of the nose, and dorsal side of the hands, fingers, and toes. (See 'STING-associated vasculopathy with onset in infancy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Josie A Pielop, MD, who contributed to an earlier version of this topic review.