On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.1 Rio de Janeiro Jan./Feb. 2004
CONTINUING MEDICAL EDUCATION
Bernardo GontijoI; Luciana Baptista PereiraII; Cláudia Márcia Resende SilvaIII
Professor of Dermatology, UFMG Faculty of Medicine. Ph.D. in Medicine, UFMG.
Coordinator of the Pediatric Dermatology Ambulatory Clinic, Dermatology Service,
Hospital das Clinicas, UFMG
IIAssistant Professor of Dermatology, UFMG Faculty of Medicine. Master's Degree in Medicine, UFMG. Lecturer at the Pediatric Dermatology Ambulatory Clinic, Dermatology Service, Hospital das Clinicas, UFMG
IIIMaster's Degree in Dermatology, UFMG. M.D. and Tutor at the Pediatric Dermatology Ambulatory Clinic, Dermatology Service, Hospital das Clinicas, UFMG
As a result of increased knowledge on angiogenesis, vascular anomalies have been separated into tumors and vascular malformations. Vascular malformations, the subject of this review, are classified either by the nature of the vessels (capillary, arterial, venous or lymphatic), type of flow (high or low) or even by distribution (localized or diffuse). Furthermore there are the complex-combined malformations, a feature present in most vascular syndromes. A review of the clinical aspects, diagnosis and treatment of vascular malformations is presented in this paper.
Key words: classification; diagnosis; vascular diseases/complications; vascular diseases/congenital; vascular diseases/therapy.
Vascular lesions present classification difficulties, confusion and overlapping. After many attempts at making the classification more accurate, better understanding of angiogenesis led Mulliken and Glowacki in 1982 to suggest that vascular anomalies be divided into two categories: hemangiomas and vascular malformations.1 These manifestations are differentiated based on their cellular characteristics, clinical appearance and natural history. Hemangiomas are characterized by the proliferation of endothelial cells. They are present at birth in only 40 % of cases (generally as precursor lesions). Their post-nascent growth is rapid, followed by slow and spontaneous progression; the female-to-male ratio is 5:1. Vascular malformations show a normal cycle of endothelial cells. Their lesions, of which 90% are recognized at birth, show a proportional growth to a child's and do not show spontaneous involution. The female-to-male ratio is 1:1.1
In 1996 this classification was adopted, with modifications, by the International Society for the Study of Vascular Anomalies. As such, vascular lesions were divided into tumors (hemangioma and other tumors) and vascular malformations (capillary, venous, lymphocytic, arterial and combined).2 This dichotomy is not absolute. There may be coexistence of tumors and malformations.3 Vascular tumors (hemangioma of infancy and other tumors) were the subject of an article in Continuing Medical Education in Dermatology, published in the previous issue of the Brazilian Annals of Dermatology. The present review focuses on vascular malformations.
Vascular malformations are categorized in accordance with the nature of vascular channels (capillary, arterial, venous or lymphatic). It must be emphasized that the coexistence of different vessels in a single lesion is common. In addition, various affections show characteristics, distribution patterns and associations with other common morphological alterations. This is why they are referred to as syndromes and are usually denoted with eponyms.
Vascular malformations may be divided into two categories: either high or low flow. High flow malformations include arterial malformation (AM), arteriovenous fistula (AVF) or arteriovenous malformation (AVM). Low flow vascular malformations include venous malformation (VM), lymphatic malformation (LM) and capillary malformation (CM). In addition, there are combined complex malformations in which most syndromes with eponyms are filed: lymphatic capillary (LCM), capillary venous (CVM), venous lymphatic (VLM), capillary arterial (CAM), venous-lymphatic capillary (VLCM), venous arterial capillary (VACM), and lymphatic venous arterial capillary malformations (LVACM). Vascular malformation may also be classified as localized or diffuse. With respect to prognosis, they may be inconclusive, causing cosmetic or functional problems, or even threatening the patient's life. The diagnosis is clinical in most cases, but radiological studies may be useful to delimit the malformation, detect associated anomalies and define treatment.4 The multidisciplinary approach is required not only for diagnosis, but also for treating vascular malformations.5-7 (Chart 1).
Although usually sporadic, vascular malformations may eventually be familial and genetically determined.8 In four autosomal dominant vascular disorders (hereditary hemorrhagic telangiectasia, familial glomangiomatosis, familial cerebral venous malformations, and cutaneous venous malformations and multiple mucosas), the defective gene has already been localized. Mutant genes are also known for two recessive disorders: ataxia/telangiectasis and Fabry's disease.2
CAPILLARY VASCULAR MALFORMATIONS
Port-wine stain, misnamed as flat hemangioma, is frequently referred to as nevus flammeus, though this expression is also used as a synonym of salmon patch. As these two lesions have distinct significance and prognoses, the term nevus flammeus must be dropped. Port-wine stain is a congenital vascular malformation that shows no tendency toward involution. It is frequently unilateral and segmentary, and usually respects the medial line. It increases in proportion to the child's growth, and may be present on any area of the body. The face and cervical regions are the most common sites (Figures 1A and 1B). The lesions may be pink during infancy, but tend to become wine-colored with age. From the outset port-wine stains are totally macular, but with age and especially after the fourth decade of life, they may show an irregular, thick and nodular surface.9 In few children, the lesion may become lighter with age, but total remission is unusual.10 The lesion turns slightly pale to when pressed with the fingers. Its color is intensified with a child's tears. Microscopically, port-wine stain consists of dilated and mature capillaries in the dermis without any evidence of cellular proliferation. The etiology of the lesion is not known. There is speculation as to fragility in the capillary walls and a deficit in the number of perivascular nerves leading to a neuromodulation deficiency of the vascular flow at the lesion site.11 In two studies performed, port-wine stain was found in 0.36%12 and 1.2%13 of NR.
There are case reports of familial,14 acquired15,16 and bilateral and symmetrical port-wine stains.17
The therapy of choice is Pulsed-Dye Laser. The treatment must take place at the earliest possible time, given that the youngest children usually require a fewer sessions and show more favorable therapeutic results. Also, the result is better in localized lesions on the face and trunk in relation to those found on the extremities. Hypertrophy of the soft tissues does not respond to the laser, and surgical correction may be necessary.6,18-20
Sturge-Weber Syndrome is characterized by the presence of port-wine stains on the first branch region of the trigeminal nerve, with ipsilateral vascular anomalies on the leptomeninges. One or more of the following signs or symptoms may be present: epilepsy, hemiparesis or hemiplegia, intracranial calcifications, cerebral atrophy and vascular lesions of the ipsilateral carotid in association with glaucoma. It is worth emphasizing that only 10% of the carriers of port-wine stain appearing in the area innervated by the ophthalmic branch show this syndrome.2
Patients showing port-wine stain on the face and glaucoma without meningeal anomalies, or meningeal angiomas without port-wine stain on the face do not satisfy the criteria to be considered carriers of Sturge-Weber syndrome.21 Patients whose vascular stains are distributed only along the maxillary sensory branch and mandible regions do not present a risk of neuro-ocular disease. However, repeated ophthalmologic assessment and computerized tomography of the cranium are indicated only for patients with port-wine stain on the ophthalmic area.21
The risk of glaucoma grows when there is joint affliction of the ophthalmic and maxillary branches, which may occur in 45% of patients. In 50% of patients intracranial lesion symptoms emerge in the first year of life but very rarely is there onset after age 20 years. Convulsions, which may occur in 80% of cases, are usually premature, with onset in the first three months of life. Hemiplegia is reported in up to 30% of cases, and mental retardation in 60%. Lesions in the oral mucosa may be present.22
Phacomatosis pigmentovascularis is a syndrome combining port-wine stain and other cutaneous lesions, such as epidermal or melanocytic nevus (type 1), dermal melanocytosis with or without anemic nevus (type II), nevus spilus with or without anemic nevus (type III), or dermal melanocytosis and nevus spilus with or without anemic nevus (type IV). The letter A is appended when involvement is merely cutaneous; letter B when systemic involvement is associated (hypoplastic larynx, subglottic stenosis, calcifications in the central nervous system, cerebral atrophy, and scoliosis).6,23,24
Beckwith-Wiedemann syndrome includes a capillary malformation on the central region of the forehead or upper eyebrows. It resembles persistent salmon patch in association with a somatic and visceral overgrowth, with macroglossia, enlarged kidneys and exomphalos.25
Robert's syndrome is characterized by severe tetraphocomelia, leporine lip and palatine fissure, mental retardation and few possibilities for survival. Medial facial capillary malformation is usually present.26
Salmon patch was first reported by French physicians in 1881 under the term tache sanguine. But it was Unna, the German dermatologist, who first gave it a detailed description in 1884. Various names are used, such as capillary telangiectasis, telangiectasia nevus of the nape of neck, Unna nevus, erythema of the nape of neck, hemangioma of the nape of neck and wine-stained nape of neck. Lesions found on the eyebrows and forehead are commonly known as 'angel's kiss'. The occipital lesions are considered to be the marks of a stork's bite.27 A genetic component, possibly autosomal dominant, is thought to be involved in the etiology of salmon patch.
It is clinically characterized by flat pink or reddish lesions that often have telangiectasias localized on the occipital region, neck, glabella, forehead, upper eyebrows and nasolabial regions (Figure 2A). Lesions usually project when the child cries and may disappear totally when compressed. They presumably consist of ecstatic dermal capillaries, which represent persistent fetal circulation patterns in the skin. They are usually localized on the medial line, except with eyebrow lesions. And they must be differentiated from port-wine stain, which tends to be unilateral and more wine-like. Salmon patch is usually present on more than one site in the same newborn.27,28
The frequency reported in the literature varies from 1.5% to 74%. The most affected regions are the nape of the neck (37.1%), glabella (19.6%), eyebrows (15.4%), nose (1.5%) and upper lip (0.5%).27 Eyebrow lesions appear to regress more rapidly than those of the glabella, and the latter more rapidly than those localized on the nape.27,29 Most lesions disappear by age six. Those localized on the eyebrows and glabella disappear during the first year of life. The persistence of the stain on the occipital region in adults is frequent and occurs in up to 50% of individuals.30
Sacral medial telangiectatic vascular stain
As we have already seen, port-wine stain is characterized by being unilateral and it persists unaltered during the course of one's lifetime. By contrast, salmon patch is often localized on the medial line (except for the localization on the eyebrows) and shows spontaneous involution (except for the localization on the occipital region, which persists in adult life for roughly 50% of patients).
Angiomatous spots localized on the medial line of the sacral region, usually in a butterfly shape that tends to persist during one's entire lifetime, can be seen in newborns. They are not usually classified as port-wine stains or salmon patches (Figure 2B). These lesions appear to be associated with bifid spine, spinal dysraphism, intraspinal masses, imperforated anus, and kidney or genital abnormalities as occur with sacral hemangiomas. They show very similar characteristics and progression to salmon patches on the nape. Some authors prefer using the term sacral telangiectatic vascular nevus for these lesions. Others have already included them among salmon patches.31
Essential telangiectasia (localized or generalized) is a vascular alteration frequently found in women. It is typically localized on the lower limbs. Onset occurs during or after puberty. It may present as irregular fine lines, or as dot- or star-like macules either with or without an anemic halo.5,6
Unilateral nevoid telangiectasia occurs predominantly in women. Onset occurs during puberty and may intensify with pregnancy. A high number of estrogen and progesterone receptors has been demonstrated in the skin areas involved.6
Benign hereditary telangiectasia is a family disorder characterized by the presence of cutaneous and labial telangiectasias. As opposed to Rendu-Osler-Weber syndrome, it does not show any visceral hemorrhaging.6
Generalized essential telangiectasis is another syndrome appearing sporadically in adult females.6
Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome) is an autosomal dominant disorder manifested during infancy or adolescence with telangiectasias on the face, tongue, lips, nose, conjunctiva, fingers, ungual bed, liver, lungs, spleen, pancreas and brain.5 Bleeding in the mucouses (recurrent epistaxis with onset during infancy and aggravation in adulthood) and in the visceras (bleeding in the upper and lower gastrointestinal tract) may cause anemia. Hereditary hemorrhagic telangiectasia is characterized by genetic heterogeneity with variable phenotypes. Two defective genes have already been found (9q33-34 and 12q). Electrodissection, Laser (Nd: YAG, carbon dioxide or argon), and sclerotherapy have been used to stanch the hemorrhaging.2,6
Ataxia/telangiectasia (Louis-Bar syndrome) is a recessive autosomal disorder that is usually fatal for patients up to their twenties. Cerebellar ataxia (cerebellar degeneration with progressive motor degeneration) is associated with the presence of ocular telangiectasias (mainly in the bulbar conjunctiva, close to the corner of the eye). Cutaneous telangiectasia may also occur on the face, throat and dorsal aspect of the hands and feet. Humoral immunodeficiencies (IgA and IgG-2 deficiency) and cellular ones (lymphopenia and reduction of CD4+) in association with repeated respiratory infections are characteristic. Telangiectasia usually emerges at three years of age, and cerebellar ataxia in the second decade of life. Endocrinologic dysfunction (insulin-resistant diabetes, gonadal insufficiency and growth retardation), premature aging, ephelides and loss of subcutaneous tissue are also observed. Syndrome carriers show a risk of cancer 61 to 184 times higher than in the general population (mainly lymphomas, leukemias and carcinomas). These neoplasias represent the main cause of death. The genetic defect is found in chromosome 11q22-23.2,5,6
Congenital telangiectatic cutis marmorata
Congenital telangiectatic cutis marmorata (van Lohuizen Syndrome) is a reticulated vascular lesion with a blue-violet color. It is usually present at birth. As opposed to reticular livedo it is always visible and may also be accentuated with cold weather (Figure 3). Cutaneous lesions tend to improve spontaneously, above all in the first two years of life. They may be localized (89% of cases) or more extensive (11%). But there are no reports on generalized forms.32 Its pathogenesis is not known, but autosomal dominant inheritance with variable penetrance, or the presence of a lethal gene, which survives due to the phenomenon of mosaicism,, are among the hypotheses formulated.32 A functional defect of vascular sympathetic innervation (neurogenic tonus) may explain cutaneous lesions.33 Associated anomalies include body asymmetry, other vascular anomalies, glaucoma, congenital cutaneous aplasia, palatine fissure, mental or psychomotor retardation, cutaneous atrophies, and ulcerations.32,33 The pulsed-eyed laser may be used to treat residual cutaneous lesions.6
Adams-Oliver syndrome, with autosomal dominant inheritance, is formed by congenital telangiectatic cutis marmorata in association with multiple lesions of cutaneous aplasia on the scalp, either with or without underlying bone defects and defects in the limbs.6
LYMPHATIC VASCULAR MALFORMATIONS
Lymphatic malformations are present congenitally in 60% of cases. They become apparent by the second year of life in 90% of patients. Usually, they do no regress spontaneously, and their volume may increase with hemorrhages, liquid build-up or inflammation.5,6
Macrocystic lymphatic malformations (cystic hygroma) are characterized as large, soft lesions with a smooth surface and translucent with normal skin or blue with overlying skin. They are localized typically in the rear triangle of the throat. Onset may occur in the popliteal space, and retroperitoneal and virilian areas. They are caused by a communication defect between the lymphatic system and the fetal venous which, if it is reestablished later, may result in the regression of hygroma and improvement of peripheral edema. Cystic hygroma must be differentiated from the other cranial-cervical masses, such as encephaloceles and cystic teratoma. Studies show an increase in a-phetoprotein in the amniotic liquid during the pre-natal period. This lymphatic malformation may be associated to fetal hydrops, which reduce the child's probability of survival.5,6,34
Microcystic lymphatic anomalies (circumscribed lymphangioma) are characterized by the small vessel grouped in plaques, on the skin or in mucouses. They have a translucent content or are slightly hemorrhagic. They predominantly affect the cervical-facial region, axillae, thorax and extremities (Figure 4). There might be hypertrichosis on the site.5,6
Histopathologically, microcystic lymphatic malformations are characterized by fine vessel walls with no blood within. They are localized in the dermis, which may or may not have lymphocytes around. The presence of blood within the vessels may indicate recent hemorrhaging or a combined, usually venous or lymphatic, malformation. With macrocystic lesions, large cisterns are found which do no communicate directly with the lymphatic system. In mixed lymphatic malformations (macro- and microcystic), the deep muscular cisterns communicate with the superficial dermis by means of a complex network of anastomoses.6
If the clinical diagnosis leaves any doubts about the lesion's lymphatic origin, the following techniques may be used: ultrasound to demonstrate anechoic or hypoechoic and homogenic cysts; computerized tomography to reveal hypodense cysts; and magnetic resonance to show hypointense cystic spaces on T1. A puncture of the lesion may be carried out directly to show the presence of a clear liquid.6 The lymphatic and vena malformations show patterns similar to magnetic resonance. As opposed to other lesions, no vessel or lobular architecture is demonstrated. The contrast medium may be useful, because lymphatic malformations do not intensify with the contrast. The main role of magnetic resonance is to determine the extension and infiltration of the deep tissues and assist in the differential diagnosis with other soft tissue tumors.35
Treating lymphatic malformations is difficult. Lesions that end up obstructing the respiratory tract require excision, aspiration, tracheostomy and sounding to maintain patient feeding. Infections must be treated with antibiotics. Surgical removal is indicated when the lesion interferes with the function, causes aesthetic problems or gets easily infected. For localized lesions, complete excision is possible. In diffuse forms usually associated with normal tissues, such as nerves, more careful excision becomes necessary, usually in several sessions. As for benign lesions, there is no indication whatsoever to excise nerves or muscles. Treatment may also be attempted with sclerosing agents, such as bleomycin, OK-432, also known as picibanil (a dead fungus of the Streptococcus pyogenes bacteria group), a solution of sodium tetradecyl sulphate, with a potential risk of recurrence and/or infection.5,7,34,36,37
Turner's syndrome is defined as a gonadal dysgenesis due to chromosome X being absent or defective (46XO). It is frequently associated with congenital lymphatic malformations, such as hypoplasic lymphatic vessels, which are responsible for the presence of lymphedema in the lower limbs at birth; in most cases these disappear within a few months or years. Other malformations, such as cystic hygroma, fetal hydrops and ascites, may be detected from the second trimester on by ultrasound. Phenotypically, it is also characterized by physical features such as short stature, large thorax with a wide space between the nipples, short webbed neck (pterygium colli), ogival palate, hypoplastic nails, malformed ears and multiple melanocytic nevi.34
Noonan's syndrome is phenotypically similar to Turner's syndrome, but the cariotype is normal (46XY or 46XX). It is characterized by physical features such as short stature, a short and thick throat, hypertelorism, epicanthis, low hair line and micrognathia. As opposed to what occurs in Turner's syndrome, the lymphedema is usually persistent in adult life, either in a stationary or slowly progressive form. Aplasia or hypoplasia of the lymphatic vessels and lymphangiectasis can also be observed. The thick neck can be explained by the regression of cystic hygromas with collateral formation of lymphatic channels. Questions remain as to whether autosomal dominant inheritance characterizes this syndrome.34
VENOUS VASCULAR MALFORMATIONS
Venous vascular malformations span over a wide spectrum, varying from isolated cutaneous ectasias to voluminous lesions involving manifold tissues and organs. They are soft and compressible, and show no alteration in skin temperature, thrill or bruits. They are frequent and wrongly called cavernous hemangiomas. Pure venous malformations usually exhibit blue coloration on the skin or in the overlying mucosa, while combined venous capillaries exhibit a hue that ranges from dark-red to violet.5,6
The venous malformations are hemodynamically inactive, with a low flow. Their volume increases when the person is standing or doing physical efforts. They are present at birth, and worsen progressively during infancy, and, to a lesser degree, during adulthood. Their volume may also increase with pregnancy or trauma.2,38 They do not usually involve only the skin, but also underlying structures, such as muscles and fascia. There is no overgrowth of the limbs, which differs from combined vascular malformations, such as Klippel-Trenaunay syndrome. There may be refinement, demineralization, hypoplasia or lytic changes in the underlying bones in up to 71% of cases.2
The diagnosis is clinical for most cases, but a simple radiography may reveal phleboliths (calcified thrombi) already at age two or three years. These round calcifications are pathognomic of venous vascular lesions. Simple radiography can also be useful to assess bone distortions. Magnetic resonance is the best examination to delimit vascular malformation.6
Venous thrombosis is a regular complication, and the thrombi may be palpated at the point of pain. Another possible complication is the development of consumption coagulopathy for stasis in the ecstatic vascular canals. With stasis there is formation of microthrombi and, secondly, consumption coagulation factors. Platelet numbers are moderately low (usually around 100,000/mm3). However these are higher than what is observed in Kasabach-Merritt syndrome. Similar alterations may occur in lymphatic or combined (venous lymphatic) malformations. Treatment is carried out with low-molecular-weight heparin. The possibility of consumption coagulopathy must be investigated prior to undertaking any invasive procedures.2,5,39
Venous vascular malformations cannot be eradicated completely. The usual treatment is sclerotherapy, with a local injection of sclerosing solutions, like 95% alcohol or sodium tetradecyl sulfur 1% for small lesions. Surgical resection may be performed after successful obliteration by sclerotherapy. The embolization of arteries sustaining the malformation is counter-indicated since it may provoke tissue necrosis. Photocoagulation by laser may obstruct small superficial vessels. Surgical excision is the definitive therapy, often rendered impossible however by anatomic, esthetic and functional limitations.5,40
Familial cerebral venous malformations constitute an autosomal dominant disorder. But the gene carriers may remain free of symptoms. Patients may suffer fainting, cerebral hemorrhaging, and neurological or cephalic deficits. Magnetic resonance demonstrates venous malformations found on the skin and retina as well. There is probably a genetic heterogeneity, but with a defective gene involved. A defective gene was already found on chromosome 7q 11-22. It was mapped in several families with this syndrome, but was absent in others.2
Cutaneous venous malformations and multiple familial mucouses are dominant autosomal diseases consisting of cutaneous-mucosa venous malformations whose defect is found in chromosome 9p. The cutaneous lesions resemble blue rubber bleb nevus syndrome lesions, but there is no involvement of the gastrointestinal tract.2,6
In blue rubber bleb nevus (Bean's syndrome), vascular malformations are present on the skin and in the vessels. The cutaneous lesions are characterized by blue nodules, isolated or in groups. They are soft, and can either be painful or not. Cases exist in which the violet color is absent or the lesions resemble an elastic nipple (rubber bleb). Visceral lesions mainly afflict the gastrointestinal tract (esophagus, stomach, small or large intestines, anus, and mesentery). There is usually recurrent bleeding, ferroprive anemia and, more rarely, hypovolemic shock. The oral cavity, nasopharynges, genitalia, bladder, brain, spinal medulla, liver, spleen, lungs, bones and muscles may also be affected.6
Histologically, the lesions show a network of vascular lakes, delineated by flattened endothelial cells and absence of glomic cells.6
Cutaneous vascular lesions may be treated with sclerotherapy, excision, cryosurgery and Nd: YAG laser. Visceral lesions with bleeding might require photocoagulation or surgical resection.6
ARTERIAL VASCULAR MALFORMATIONS
Arterial malformations (atresia, ectasia, aneurysm or coarctation), arteriovenous malformations (diffuse or localized conglomeration of arteries and vessels with microscopic vascular fistulas) and arteriovenous fistulas (shunts between the arterial branch to neighboring veins) are high-flow vascular anomalies characterized by increased local temperature, thrill and bruit.5,38 Pure arterial vascular malformations, such as aneurysm, stenosis and ectasias, rarely occur on the skin as symptomatic lesions. When the skin is involved, as opposed to the brain, an arteriovenous fistula is usually the result of trauma.6
COMBINED VASCULAR MALFORMATIONS
Vascular anomalies may occur jointly with other errors of morphogenesis in related mesenchymal structures, such as those of the bone tissue. Many of these disorders are better known by their eponyms.
Arteriovenous Malformations (AVM)
Arteriovenous fistulas show an epicenter called nidus consisting of arteries that feed and increase vein volumes. They may be present at birth or become evident in early infancy. They never regress spontaneously. Puberty or trauma may trigger their growth. They are clinically characterized by a mass that is covered over with normal or angiomatous skin, which is usually tense or shiny with increased heat, thrill and bruit on the site. With AVM progression, drainage veins become more evident, tortuous and distended (Figure 5). The hemorrhage is an important complication that can put the patient's life at risk.
Doppler ultrasound may be useful as a screening method, because it is a non-invasive examination capable of diagnosing a vascular lesion and differentiating it from a solid tumor mass. In addition, it allows us to distinguish vascular malformations consisting of arterial vessels, such as (high flow) AVM, from others whose arterial flow is absent (low flow).41 Magnetic resonance better shows lesion extension as well as differentiates the AVM from a hemangioma, and venous or lymphatic malformation.6 Invasive examinations of the venous system (venography) and of the arterial system (arteriography) are carried out only by planning and performing the treatment.7
As for prognosis, arteriovenous fistula is the most predictable vascular malformation. It can cause the destruction of local tissues and systemic effects. Partial excision or linking of the feeder artery may set off lesion growth and considerably worsen the prognosis. Alterations of a Kaposi pseudo-sarcoma type may be initiated on the skin at the region affected by the arteriovenous fistula.6
The arteriovenous fistula is not usually treated in its quiescent phase. Premature embolization or surgical treatment in these phases are controversial and must only be indicated when it can be performed easily. Linking or proximal embolization of the feeder arteries are counter-indicated, because the neighboring arteries grow and increase the lesion volume. The treatment must be conducted only by experienced individuals, preferentially in a multidisciplinary approach.7 The following therapeutic resources may be employed: transcatheter embolization of the nest, accompanied by pulsed-dye laser for residual skin lesions; superselective arterial embolization of the nest and surgical resection usually performed 24 to 72 hours after arterial embolization.6,42
Wyburn-Mason syndrome (Bonnet-Dechaune-Blanc syndrome)
Components of this unilateral retinoic arteriovenous malformation syndrome involve the optic and orbital nerves, ipsilateral arteriovenous malformation of the brain and ipsilateral vascular cutaneous malformation (usually with increased local temperature and thickness). This cutaneous vascular malformation does not accompany the trigeminal nerve, thereby differentiating it from port-wine stain.6
This does not show a retinoic arteriovenous fistula, but exhibits vascular anomalies in the conjunctiva, ipsilateral thalamo-encephalic AVM and angiomatous patch in the contra-lateral frontal region.6
Also called cutaneous-meningeal-spinal angiomatosis, this syndrome consists of cutaneous AVM and in the spinal medulla localized on the corresponding segment of the dermatome involved.6,22
This syndrome associates port-wine stain, venous malformations and limb hypotrophy (venous or deep arterial hypotrophy).6
This is the expression used to describe an angio-osteo-hypertrophic condition whose etiology is not known and phenotype, highly variable. The combination of a port-wine stain (capillary VM), tissue edema (lymphatic and venous VM) and bone overgrowth is called Klippel-Trenaunay syndrome. Later, Parkes-Weber described the syndrome as having a presence of arteriovenous anastomosis on the affected limb. They thus had their names added to the eponym. The bone overgrowth seems to be secondary to an embrionary defect of the mesoderm that would also be responsible for vascular anomalies. The other hypothesis suggests that the bone hypertrophy would be due to increased osteogenic function. Some of the veins (the lateral marginal thigh vein) may represent persistent embrionary veins. In family studies, only one monozygotic twin is affected, which suggests somatic mutation in premature embrionary development.6
The typical triad is macromelia, varicosities and port-wine stain, with unilateral affection and presence of the latter since infancy.34 The most common localization is the anterolateral region of the thigh in a geographic pattern. Clear and hemorrhagic lymphatic vessels may be present on the surface and there is an inadequate venous return (Figure 6).6 When there are arteriovenous fistulas along the affect limb, heat, thrill and bruit are encountered mainly at the level of the joints. There is a description in the literature of the presence of this syndrome on the face.43
Complications like increased limb size, lytic bone lesions, pathological fractures, cutaneous ulceration, cutaneous alterations of a Kaposi's pseudosarcoma type, and a rapid heart beat with congestive cardiac insufficiency may occur. Vascular anomalies associated with the trunk and abdomen may provoke hematuria, intestinal bleeding, protein-losing enteropathy and hemothorax.6
The treatment is conservative. The lymphedema and venous edema must be cared for by using palliative measures, such as elastic compresses. On the other hand, it should only be permitted when a Doppler assessment confirms adequate functioning of the deep veins. Frequent lymphatic draining (massage) is useful to minimize the lymphedema. Varicose veins may be treated surgically. Aggressive surgical procedures may cause fibrosis and worsen the lymphedema. If there is an intense discrepancy in limb size, corrective shoes must be used to prevent scoliosis. If the difference is greater than 8 cm, epiphysis surgery must done, preferable when the child is between ages 11 and 13 years. The port-wine stain may be reduced with the use of the pulsed-dye laser. Bleeding may be treated with electrocoagulation or with Nd YAG Laser.6,34
Proteus syndrome was recognized for the first time as a distinct nosological entity in 1979 by Cohen and Hayden. They described it as a new hamartomatous syndrome.44 In 1983, Wiedman suggested the name Proteus syndrome for the disease. He described four cases with the following characteristics: partial gigantism of the hands and feet, pigmented nevus, hemi-hypertrophy, subcutaneous tumors, macrocephaly and other cranial and visceral anomalies. The name derives from the Greek god Proteus who was able to transform himself so as to avoid being captured. Coining this term was timely given that the syndrome is characterized by large morphological variations in appearance and progression. The most famous patient was Joseph Merrick, whose story was told in a book and film entitled The Elephant Man. Initially considered to be a carrier of neurofibromatosis, the diagnosis of Proteus syndrome was accepted by 1988 in the wake of Cohen's studies.44
The disease is thought to be a congenital hamartomatosis affecting three embryo layers, resulting in excessive tissue growth. Palmar and plantar cerebriform hyperplasia is one of the characteristics of the syndrome (Figure 7A). Another typical finding relates to cutaneous tumors that exhibit a wide histological variety (verrucous epidermal nevus, lipomas, collagenomas).2-45
Vascular malformations are rather constant in Proteus syndrome: Port-wine stain (Figure 7B), macrocystic and microcystic type lymphatic malformations, combined vascular malformations of the limbs, such as Klippel-Trenaunay syndrome (low flow capillary and venous malformations and lymphatic malformations with gigantism of the affected limb). No observations have yet been made of high flow vascular malformations, like the arteriovenous fistula of Parkes-Weber syndrome.2
In Maffuci syndrome there is coexistence of vascular anomalies (lymphatic and venous) associated with bone and exostoses and enchondromas. It is a rare condition that seems not to have a hereditary character. It is usually not detected at birth, with bone lesions appearing in the first years of life. Vascular lesions appear later, either uni- or bilaterally. These patients may develop fusiform cell hemangioendotheliomas (today considered reactive vascular proliferation, which is secondary to a preexistent vascular malformation, more than a real tumor). The malignant transformation, usually chondrosarcoma, occurs in 20 to 30% of patients.37
This is a familial syndrome consisting of multiple subcutaneous vascular malformations, pseudopapilledema and macrocephaly.5
Solomon's syndrome includes capillary vascular and venous anomalies in any localization on the skin, arteriovenous malformation of the central nervous system in association with skeletal abnormalities (bone hypertrophy), and epidermal nevus.5
This is an autosomal dominant disease in which a mutation occurs on chromosome 10 (10q23). It clinically resembles Cowden's syndrome. The major clinical characteristics are macrocephaly, multiple lipomas (capsular or diffuse and infiltrating), polyps on the distal ileus and colon, Hashimoto thyroiditis, pigmented macules on the glans penis and vascular malformations that may be capillary, venous, lymphatic and possibly arteriovenous.24-37
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Rua Domingos Vieira, 300 - Conj. 505 - Sta. Efigênia
Belo Horizonte MG 30150-240
Tel/Fax: (31) 3241-1185 / 3241-6691
in December, 05rd of 2003
Approved by the Editorial Council and accepted for publication in December 10th of 2003
* Work done at tthe Pediatric Dermatology Ambulatory Clinic, Dermatology Service, Hospital das Clinicas, UFMG.
Questions and Answers to Questions
1. Em relação aos hemangiomas e malformações vasculares, assinale a alternativa incorreta.
a) A relação de freqüência no sexo feminino e no masculino das malformações vasculares é de 1:1, enquanto nos hemangiomas é de 5:1.
b) As malformações vasculares apresentam proliferação das células endoteliais nos primeiros anos de vida, o que explica seu aumento proporcional ao crescimento da criança.
c) Cerca de 90% das malformações vasculares são reconhecidas ao nascimento.
d) Os hemangiomas apresentam crescimento rápido pós-nascimento, seguido de involução espontânea lenta.
2. As alternativas abaixo representam malformações vasculares de baixo fluxo, exceto:
a) blue rubber bleb nevus;
b) higroma cístico;
c) síndrome de Parkes-Weber;
d) síndrome de Rendu-Osler-Weber.
3. Em relação à síndrome de Sturge-Weber, assinale a alternativa incorreta.
a) Epilepsia, hemiparesia, hemiplegia, atrofia cerebral são manifestações neurológicas da síndrome.
b) Lesões na mucosa oral podem estar presentes.
c) O risco de glaucoma aumenta quando há acometimento dos ramos oftálmico e maxilar em conjunto.
d) Os pacientes com mancha em vinho do Porto na área de inervação do nervo oftálmico apresentam risco de 90% para a síndrome de Sturge-Weber.
4. Em relação às malformações vasculares capilares, assinale a alternativa incorreta.
a) A cútis marmórea telangiectásica congênita desaparece em praticamente todas as crianças, de forma total ou parcial.
b) A mancha salmão presente na região occipital persiste em até 50% dos adultos.
c) A mancha vascular telangiectásia medial sacral, geralmente em forma de borboleta, associa-se freqüentemente com malformações do sistema nervoso central, principalmente com a espinha bífida.
d) A síndrome de Louis-Bar geralmente associa telangiectasias, ataxia cerebelar e imunodeficiências.
5. As alternativas abaixo descrevem características da telangiectasia hemorrágica hereditária (síndrome de Rendu-Osler-Weber), exceto:
a) as lesões já estão presentes ao nascimento, ocor rendo a maioria das mortes no período neonatal;
b) é doença autossômica dominante, já tendo sido encontrados dois genes defeituosos (9q33-34 e 12q);
c) sangramento do trato gastrointestinal, epistaxes e hemoptises podem causar anemia;
d) sangramentos nas mucosas pela presença de telangiectasias na face, língua, lábios, nariz e conjuntiva caracterizam a síndrome.
6. Em relação às malformações vasculares linfáticas, assinale a alternativa correta.
a) A dosagem de alfa-fetoproteína no líquido amniótico no período pré-natal está aumentada nas malformações linfáticas microcísticas.
b) As malformações linfáticas estão presentes ao nascimento, nunca involuem com o crescimento e podem aumentar de volume por hemorragia, acúmulo de líquidos ou inflamação.
c) Na síndrome de Noonan há uma alteração cro-mossômica, e a maioria das crianças acometidas apresenta o genótipo 46XO
d) O uso de agentes esclerosantes, como o OK-432, está indicado em algumas formas de malformações linfáticas.
7. Em relação às malformações vasculares linfáticas, assinale a alternativa incorreta.
a) A punctura direta da lesão pode ser útil para diagnosticar uma malformação vascular linfática pelo extravasamento de líquido claro.
b) A ressonância magnética sempre diferencia uma malformação vascular linfática de uma venosa, apesar de as duas serem malformações vasculares de baixo fluxo.
c) As malformações vasculares linfáticas macrocísticas geralmente associam-se com hidropisia fetal e ascite, aumentando as possibilidades de morte neonatal.
d) O pterygium colli é provavelmente secundário a um higroma cístico que apresentou regressão e formou uma membrana residual ligando a cabeça ao pescoço.
8. Em relação às malformações vasculares venosas, assinale a alternativa incorreta.
a) A radiografia simples pode ser diagnóstica quando se encontram flebólitos.
b) São hemodinamicamente inativas, de baixo fluxo, seu tamanho não se alterando com a posição do paciente ou com esforços físicos.
c) Pode haver desmineralização, hipoplasia ou alterações líticas nos ossos subjacentes em torno de 70% dos casos
d) Podem apresentar piora com o avançar da idade, durante gravidez ou com traumas.
9. As alternativas abaixo descrevem possíveis complicações das malformações vasculares venosas, exceto:
a) hemorragias cerebrais e retinianas;
b) sangramentos com anemia ferropriva e, mais rara mente, choque hipovolêmico;
c) síndrome de Kasabach-Merritt com plaquetas abaixo de 100.000/mm3 e outros distúrbios da coagulação;
d) trombose venosa profunda.
10. As alternativas abaixo relacionam características das malformações vasculares arteriais, exceto:
a) seu tamanho altera-se facilmente com a compressão manual;
b) geralmente seu tamanho não varia de acordo com a posição do paciente;
c) a pele sobrejacente é lisa, brilhante e apresenta aumento da temperatura local;
d) presença de frêmito e sopro.
11. Assinale a alternativa incorreta em relação às malformações arteriovenosas.
a) A ligação da artéria nutridora é o tratamento de escolha por impedir o crescimento progressivo da lesão.
b) A ressonância magnética delimita melhor a extensão da lesão do que a ultra-sonografia, apesar de essa representar um ótimo exame de screening.
c) A ultra-sonografia com Doppler diferencia uma mal formação vascular de alto fluxo de uma de baixo fluxo.
d) Exames invasivos, como a venografia ou arteriografia, estão indicados para o planejamento do tratamento.
12. Em relação à síndrome de Klippel-Trenaunay-Parkes-Weber, assinale a alternativa incorreta.
a) Caracteriza-se pela tríade clássica: macromelia, varicosidades e mancha em vinho do Porto.
b) A escoliose pode ser uma complicação dessa síndrome.
c) O acometimento é geralmente unilateral, localizado em apenas um membro e presente desde a infância.
d) O uso de meias elásticas compressivas está sempre indicado no tratamento dessa síndrome.
13. Em relação à síndrome de Proteus, assinale a alternativa incorreta.
a) A hiperplasia cerebriforme palmar e plantar é um dos sinais característicos da síndrome.
b) É considerada uma hamartomatose congênita que afeta os três folhetos embrionários e tem como resultado o crescimento excessivo dos tecidos.
c) É freqüente nessa síndrome a presença de fístula arteriovenosa, à semelhança da síndrome de Parkes-Weber.
d) Mancha em vinho do Porto e malformações vasculares combinadas semelhantes às que ocorrem na síndrome de Klippel-Trenaunay são comuns nessa entidade.
14. As características relacionadas a seguir são próprias da síndrome de Maffuci, exceto:
a) anomalias vasculares linfáticas e venosas;
b) caráter genético, recessiva, ligada ao cromossoma X;
c) encondromas e exostoses ósseas;
d) transformação maligna em proporção que varia de 20 a 30% dos casos, geralmente para condrossarcomas.
15. Assinale a associação incorreta.
a) Malformações venosas cutâneas e mucosas familiares múltiplas: assemelham-se à síndrome blue rubber bleb nevus, porém sem acometimento do trato gastrointestinal.
b) Síndrome de Bannayan-Riley-Ruvalcaba: macrocefalia, lipomas múltiplos, malformações vasculares.
c) Síndrome de Cobb: angiomatose cutâneo-meningo-espinhal com malformação vascular na medula espi nhal e cutânea no segmento correspondente ao dermátomo envolvido.
d) Síndrome de Wyburn-Mason: malformação vascular retiniana e facial, acompanhando a inervação do trigêmeo como na síndrome de Sturge-Weber.
Hemangioma da infância 2003; 78(6): 651-673
1 - d 9 - c
2 - a 10-e
3 - e 11 - e
4 - c 12 - c
5 - d 13 - e
6 - b 14 - e
7 - b 15 - d
8 - e