Capillary Vascular Malformations Research Articles

Surgery for Port-Wine Stains: A Systematic Review.

Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective-systematic score of evaluation. Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result.

Developmental expression of the Sturge-Weber syndrome-associated genetic mutation in Gnaq: a formal test of Happle's paradominant inheritance hypothesis.

Sturge-Weber Syndrome (SWS) is a sporadic (non-inherited) syndrome characterized by capillary vascular malformations in the facial skin, leptomeninges, or the choroid. A hallmark feature is the mosaic nature of the phenotype. SWS is caused by a somatic mosaic mutation in the GNAQ gene (p.R183Q), leading to activation of the G protein, Gαq. Decades ago, Rudolf Happle hypothesized SWS as an example of "paradominant inheritance", that is, a "lethal gene (mutation) surviving by mosaicism". He predicted that the "presence of the mutation in the zygote will lead to death of the embryo at an early stage of development". We have created a mouse model for SWS using gene targeting to conditionally express the GNAQ p.R183Q mutation. We have employed two different Cre-drivers to examine the phenotypic effects of expression of this mutation at different levels and stages of development. As predicted by Happle, global, ubiquitous expression of this mutation in the blastocyst stage results in 100% embryonic death. The majority of these developing embryos show vascular defects consistent with the human vascular phenotype. By contrast, global but mosaic expression of the mutation enables a fraction of the embryos to survive, but those that survive to birth and beyond do not exhibit obvious vascular defects. These data validate Happle's paradominant inheritance hypothesis for SWS and suggest the requirement of a tight temporal and developmental window of mutation expression for the generation of the vascular phenotype. Furthermore, these engineered murine alleles provide the template for the development of a mouse model of SWS that acquires the somatic mutation during embryonic development, but permits the embryo to progress to live birth and beyond, so that postnatal phenotypes can also be investigated. These mice could then also be employed in pre-clinical studies of novel therapies.

Sturge-Weber syndrome: Clinico-neuroradiological features and treatment profile

Introduction: Sturge Weber syndrome (SWS) is a rare, nonhereditary genetic disorder. SWS belongs to a diverse group of Neurocutaneous disorders. A somatic mutation in the early development of cells in SWS patients causes the formation of a congenital capillary vascular malformation. SWS is characterized by nevus flammeus on the face (also called Port-Wine Birthmark), brain (leptomeningeal angioma), and eyes (glaucoma). Methods and Materials: We present three patients diagnosed with Sturge Weber syndrome who attended a teaching hospital between 2013 to 2016. The clinical, neuroradiological features and treatment of SWS patients were reviewed retrospectively from medical records. Results: Two males and females with SWS were reviewed. The facial nevus flammeus was unilateral in one patient and bilateral in two patients. The extensive nevus flammeus including the face, trunk, and upper limb was found in one patient. Epilepsy, neurodevelopmental delay, and intellectual disability were the most common presentation in the series. Episodic hemiparesis was manifested in one patient. Levetiracetam and oxcarbazepine, either single or combined, were used in every SWS patient (n=3). Six months seizure-free was obtained in a patient with SWS with combined anticonvulsant therapy. Conclusion: Drug-refractory and early-age epilepsy is associated with lower intelligence level that consequently affects poor social skill and quality of life in the patients with SWS. Sudden or gradual loss of vision is also a threat for SWS patients. Diagnosis at birth or during early age, multidisciplinary intervention, and follow-up is a must to improve absolute outcomes in the patients with SWS.

Cutaneous Nevi in Down Syndrome Patients: Prospective study

Background: Down Syndrome (DS) has been described in association with various dermatoses,however, there is scanty information in the literature regarding the frequency of cutaneous nevi among Down syndrome patients. The objective of the study: To define the frequency of different cutaneousnevi in DS patients, andto precise their different phenotypes. Patients and methods: we prospectively examined 180 Down syndrome patients. All patients underwent full body skin examination noting the type, number, size, and distribution of different nevi. Results: Different types of nevi were noted among Down syndrome patients; café au lait macules, melanocytic nevocellular nevi, and Mongolian spot were the most frequent ones. Juvenile elastoma, Becker’s nevus, nevus spilus, labial melanocytic macule, and capillary vascular malformation were also seen. Conclusion: Various types of cutaneous nevi not previously described in Down syndrome, was observed in our patients such as Becker’s nevus, nevus spilus and Juvenile elastoma.

Facomatosis pigmentovascular tipo cesioflamea: a propósito de un caso

La facomatosis pigmentovascular tipo cesioflamea se caracteriza por la presencia de una malformación vascular capilar superficial, que coexiste en la misma superficie cutánea con una melanocitosis dérmica o un nevo anémico. A su vez, esta entidad puede estar asociada a alteraciones de índole sistémico, especialmente del sistema nervioso central. Su incidencia y prevalencia son desconocidas por su baja frecuencia; sin embargo, reviste de gran importancia para los profesionales de la salud relacionados con la atención de recién nacidos. A continuación, se describe el caso de un neonato a término de 5 días de vida, que nació con una mácula azul-grisácea de gran extensión, superpuesta a una mácula eritematoviolácea, que afectaba al tronco y a las extremidades, respetando la cara, las palmas y las plantas. El diagnóstico final se hizo con base en la clínica y los paraclínicos ordenados, donde se descartó compromiso extracutáneo por medio de resonancia magnética cerebral y de columna total contrastada, fundoscopia y ecografía ocular.

Facomatosis pigmentovascular cesioflammea asociada a epilepsia focal mioclónica: Primer caso reportado en el Perú

La facomatosis pigmentovascular es un síndrome congénito muy poco frecuente, caracterizado por la presentación simultánea de una malformación vascular capilar y una lesión cutánea pigmentaria, con o sin compromiso extracutáneo. Se presenta el caso de una adolescente con epilepsia que cursa con crisis mioclónicas focales no controladas por un tratamiento farmacológico irregular, y que muestra además lesiones cutáneas compatibles con nevus flammeus y melanosis dérmica, ocular y palatina, presentes desde el nacimiento. Se trata del primer reporte en el país, de un síndrome neurocutáneo poco frecuente y de su asociación clínica con epilepsia, resaltándose además la importancia de una evaluación integral de esta entidad.

Notch Signaling in Familial Cerebral Cavernous Malformations and Immunohistochemical Detection of Cleaved Notch1 Intracellular Domain.

Cerebral cavernous malformations (CCM) or cavernomas are slow-flow capillary vascular malformations with a mulberry-like appearance, which are predominantly located in the central nervous system. CCM can occur in a sporadic or a familial form. The latter is inherited in an autosomal dominant manner, and in the majority of the fragile lesions, mutations in the genes CCM1 (KRIT1), CCM2 (OSM), or CCM3 (PDCD10) can be detected. Loss of these genes leads to numerous alterations in endothelial cell signaling resulting in a disturbed vessel architecture and function. Lower activity of Notch signaling occurs upon loss of CCM1, CCM3, or the CCM1-interacting protein ICAP1 in cell culture and animal models. Notch signaling in endothelial cells is an essential regulator of angiogenesis, arterial-venous differentiation, vascular permeability and stability, mural cell recruitment, and flux of metabolites across the vessel wall. The purpose of this chapter is to briefly summarize the current understanding of Notch signaling in familial CCM and to provide a protocol for detecting cleaved Notch1 receptor proteins on paraformaldehyde-fixed paraffin-embedded mouse tissue.

Vascular malformation in a bicuspid aortic valve

We report here a case of capillary vascular malformation developed in a bicuspid aortic valve incidentally detected during valve replacement in a 67-year-old male patient. The International Society for the Study of Vascular Anomalies (ISSVA) classification was used to classify this vascular lesion instead of using the term hemangioma. The differential diagnosis and the literature are reviewed.

PHACOMATOSIS PIGMENTOVASCULARIS TYPE IIA – A CASE REPORT

Phacomatosis pigmentovascularis (PPV) is a rare syndrome characterized by capillary vascular malformation and pigmentary nevus but with a wide variability in clinical presentation. A case of a 9-month-old patient is reported, who presented with capillary malformation and hemihypertrophy. These features typically are seen in Klippel–Trenaunay (KT) syndrome, a syndromic type of congenital vascular malformation. However, in addition, this child had large persistent Mongolian spots, the presence of which allowed us to classify this case as PPV, type II. This is a condition with a clinical course not always benign as KT syndrome. Key words: Mongolian spots, Nevus flammeus, Vascular malformations

Neurovascular Manifestations of Hereditary Hemorrhagic Telangiectasia: A Consecutive Series of 376 Patients during 15 Years.

Hereditary hemorrhagic telangiectasia is associated with a wide range of neurovascular abnormalities. The aim of this study was to characterize the spectrum of cerebrovascular lesions, including brain arteriovenous malformations, in patients with hereditary hemorrhagic telangiectasia and to study associations between brain arteriovenous malformations and demographic variables, genetic mutations, and the presence of AVMs in other organs. Consecutive patients with definite hereditary hemorrhagic telangiectasia who underwent brain MR imaging/MRA, CTA, or DSA at our institution from 2001 to 2015 were included. All studies were re-evaluated by 2 senior neuroradiologists for the presence, characteristics, location, and number of brain arteriovenous malformations, intracranial aneurysms, and nonshunting lesions. Brain arteriovenous malformations were categorized as high-flow pial fistulas, nidus-type brain AVMs, and capillary vascular malformations and were assigned a Spetzler-Martin score. We examined the association between baseline clinical and genetic mutational status and the presence/multiplicity of brain arteriovenous malformations. Three hundred seventy-six patients with definite hereditary hemorrhagic telangiectasia were included. One hundred ten brain arteriovenous malformations were noted in 48 patients (12.8%), with multiple brain arteriovenous malformations in 26 patients. These included 51 nidal brain arteriovenous malformations (46.4%), 58 capillary vascular malformations (52.7%), and 1 pial arteriovenous fistula (0.9%). Five patients (10.4%) with single nidal brain arteriovenous malformation presented with hemorrhage. Of brain arteriovenous malformations, 88.9% (88/99) had a Spetzler-Martin score of ≤2. Patients with brain arteriovenous malformations were more likely to be female (75.0% versus 57.6%, P = .01) and have a family history of hereditary hemorrhagic telangiectasia (95.8% versus 84.8%, P = .04). The prevalence of brain arteriovenous malformation was 19.7% in endoglin (ENG) mutations and 12.5% in activin receptor-like kinase (1ACVRL1) mutations. Our study of 376 patients with hereditary hemorrhagic telangiectasia demonstrated a high prevalence of brain arteriovenous malformations. Nidal brain arteriovenous malformations and capillary vascular malformations occurred in roughly equal numbers.

Topical anaesthetic effects on skin vasculature with potential implications for laser treatment

Laser treatment of vascular lesions is affected by parameters including the diameter and depth of the vessels and flow within the vessels. Topical anaesthetics are in common use prior to laser treatment but may have effects on vessel parameters and, subsequently, the efficacy of laser treatment. Eleven patients with capillary vascular malformations were investigated for vessel diameter before and after elective application of a topical anaesthetic, Eutectic Mixture of Local Anaesthetics (EMLA) (AstraZeneca) or Ametop (S&N Health), prior to pulsed dye laser treatment. EMLA contains 2.5% lidocaine ad 2.5% prilocaine, and Ametop gel contains 4% tetracaine. Patients' capillary malformations were assessed using confocal laser scanning microscopy (CLSM) (Vivascope 1500 Mavig GmbH, Munich). Six of the 11 patients recruited had EMLA topical anaesthetic, and five had Ametop. Four hundred twenty-one diameters were measured. The mean vessel diameter was 50.87 μm. Previous laser treatments undergone by each patient were noted to exclude this as a confounding variable, and no significant difference was found between topical anaesthetic groups. Statistical calculations were made using GenStat and Minitab. There is no evidence that Ametop affects mean diameter (p value is 0.361). EMLA reduces the mean diameter of vessels (p = 0.002), with a 27% reduction in post-EMLA diameter. This study demonstrates that the use of EMLA cream has a statistically significant reduction vessel diameter. As it is known that vessel diameter is important for the response of laser treatment, the use of EMLA may affect outcome.

A novel approach to port-wine stains.

ORIGINAL ARTICLE, p 669 Port‐wine stains (PWSs) are capillary vascular malformations that occur in 3 per 1000 live births. Selective photothermolysis of PWS blood vessels with the pulsed‐dye laser (PDL) is considered the gold standard of treatment. PDL is very effective at PWS clearance, with a low incidence of side‐effects.1 However, multiple treatments are required in part due to the body's normal wound healing response, which results in revascularization and regeneration of PWS blood vessels following laser exposure.2 PDL‐induced angiogenesis makes it very difficult to achieve complete clearance of PWSs. This has prompted investigation into combination therapy with antiangiogenic agents after laser irradiation to modulate the neovascularization skin response to laser damage and enhance the effects of laser therapy. Rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), was initially investigated as a potential adjuvant therapy after laser irradiation. Rapamycin is thought to have antiangiogenic properties through downregulation of hypoxia‐inducible factor (HIF)‐1α, which leads to a decrease in vascular endothelial growth factor (VEGF) production and reduction in the stimulation of VEGF by vascular endothelial cells.3 4 Both systemic and topical formulations of rapamycin have shown promising inhibition of neovascularization in the skin after laser treatment.5 6 Topical formulations are preferable in order to obviate systemic side‐effects, assuming that an appropriate depth of penetration is achievable. Initial studies with rapamycin have led to the investigation of other antiangiogenic agents such as imiquimod, which activates toll‐like receptor 7 leading to activation of antiangiogenic cytokines and reduction of angiogenic stimulators.7

Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations.

Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that presents in 10%-20% of patients with various brain vascular malformations. We aimed to report the radiologic features (phenotype) and the genotype-phenotype correlations of brain vascular malformations in hereditary hemorrhagic telangiectasia. Demographic, clinical, genotypic, and imaging information of 75 patients with hereditary hemorrhagic telangiectasia with brain arteriovenous malformations enrolled in the Brain Vascular Malformation Consortium from 2010 to 2012 were reviewed. Nonshunting, small, superficially located conglomerates of enhancing vessels without enlarged feeding arteries or draining veins called "capillary vascular malformations" were the most commonly observed lesion (46 of 75 patients; 61%), followed by shunting "nidus-type" brain AVMs that were typically located superficially with a low Spetzler-Martin Grade and a small size (32 of 75 patients; 43%). Direct high-flow fistulous arteriovenous shunts were present in 9 patients (12%). Other types of vascular malformations (dural AVF and developmental venous anomalies) were present in 1 patient each. Multiplicity of vascular malformations was seen in 33 cases (44%). No statistically significant correlation was observed between hereditary hemorrhagic telangiectasia gene mutation and lesion type or lesion multiplicity. Depending on their imaging features, brain vascular malformations in hereditary hemorrhagic telangiectasia can be subdivided into brain AVF, nidus-type AVM, and capillary vascular malformations, with the latter being the most common phenotype in hereditary hemorrhagic telangiectasia. No genotype-phenotype correlation was observed among patients with this condition.

Can we predict the outcome of 595-nm wavelength pulsed dye laser therapy on capillary vascular malformations from the first beginning: a pilot study of efficacy co-related factors in 686 Chinese patients.

Currently, there are no standardized, objective, and clinically applicable methods to predict the outcome of pulsed dye laser (PDL) therapy on capillary vascular malformation (CVM) patients. The introduction of a method that can predict the outcome prior to treatment will be valuable for both the patients and the doctors. In this study, the authors treated CVM with 595-nm wavelength PDL in Chinese patients (n = 686) and analyzed the efficacy of treatment and complications retrospectively in a 5-year period. Nearly 18 % of patients (n = 122) had 76 % or more clearing of lesions; over 52 % of patients (n = 360) had more than 50 % of clearing. The lesions in head and neck region had the best effective rate (58.3 %), followed by trunk (42.9 %) and extremities (35.6 %). The efficacy of PDL therapy is related to age, type, and location of lesions. Fifty-seven patients (8.3 %) had complications, including 2.0 % blistering (n = 14), 4.5 % hyperpigmentation (n = 31), 1.3 % hypopigmentation (n = 9), and 0.4 % hypertrophic scarring (n = 3). Based on these preliminary data, the authors established a standardized, objective, and clinically applicable equation that may be applied to predict the efficacy of 595 nm PDL therapy on a newly diagnosed Chinese CVM patients based on the age, type, and location of lesions.

Topical rapamycin combined with pulsed dye laser in the treatment of capillary vascular malformations in Sturge-Weber syndrome: Phase II, randomized, double-blind, intraindividual placebo-controlled clinical trial

Sturge-Weber syndrome (SWS) is characterized by port-wine stains (PWS) affecting the face, eyes, and central nervous system. Pulsed dye laser (PDL) is the standard treatment for PWS. Unfortunately, recurrence is frequent because of reformation and reperfusion of blood vessels. We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS. We conducted a phase II, randomized, double-blind, intraindividual placebo-controlled, clinical trial. We recruited 23 patients with SWS and facial PWS (12 women; median age 33 years, age range 17-65 years) from the University Clinic of Navarra, Spain. Four interventions were evaluated: placebo, PDL + placebo, rapamycin, and PDL + rapamycin. Clinical and histologic responses were evaluated using a chromatographic computerized system, spectrometry, and histologic analyses at 6, 12, and 18 weeks after the intervention. PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis, and showed a statistically significant improvement compared with the other interventions. The treatment was generally well tolerated. PDL was only applied to the lateral parts of the PWS area. Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS.

Gingival tissue alterations in 2 patients with port wine stain

Nevus flammeus, which is also known as port-wine stain (PWS), is one of the vascular birthmarks. PWS occurs in 0.3% of the newborns in both genders. It is a capillary vascular malformation, characterized by a pink or red stain and may involve skin, soft tissue and/or bone. There are a very limited number of reports regarding intraoral involvement of PWS. We report 2 female patients with PWS from date of birth. The first patient was an 11-year-old female who applied to our clinics for the treatment of her non-aesthetic and deviated intraoral view and discoloration of her gingiva, and the second patient was a 56-year-old female who applied for the extraction of her wisdom tooth. Extraoral examination in both patients revealed a diffuse PWS on the right side of their face over the cheek, extending from the midline. While the first patient had reddish skin, gingiva on right site her both jaws and lips, the second patient had only her upper jaw and lip. Because of the first patient' age, the treatment postponed to her 20', and the second patient did not accept any treatment. PWS is a rare and non-fatal condition; however, the unique appearance of these patients can lead to psychological problems especially in early ages.

Vascular malformation and common keratinocytic nevus of the soft type: phacomatosis pigmentovascularis revisited.

Phacomatosis pigmentovascularis is a rare syndrome characterized by the coexistence of a pigmented nevus and a cutaneous vascular malformation. We report a 5-year-old boy with all the typical findings of phacomatosis pigmentovascularis type Ia. Although its existence according to the traditional classification has been questioned, this case represents a very rare association of a capillary vascular malformation and a common keratinocytic nevus of the soft type.

Solitary Osseous Capillary-type Vascular Malformation of the Distal Humerus in a Child

Vascular malformations are abnormal proliferations of the endothelial lining of the blood vessels that are most commonly found in skin and can penetrate the local soft tissue and muscle. Only 1% of all vascular malformations are found in the bone. Skeletal vascular malformations of the long bones, including the humerus, are extremely rare entities that are particularly uncommon in children. Only 4 reports involving the humerus have been described in children previously. We present the case of an intraosseous capillary vascular malformation of the right distal humerus in a 3-year-old boy. Definitive treatment was successful with a single operation using curettage and intramedullary decompression with grafting of an osteoconductive calcium sulfate pellet filler and autogenous bone graft. This is, to our knowledge, the youngest reported case of a solitary intraosseous capillary vascular malformation involving the distal humerus.

Laser Treatment in the Management of Infantile Hemangiomas and Capillary Vascular Malformations

Vascular lesions encountered in dermatology can be divided into vascular malformations and vascular tumors, namely infantile hemangiomas (IH). Vascular malformations can further be subdivided by their flow characteristics and vessel type. Slow, or low-flow lesions are either capillary vascular malformations (CVMs), venous malformations, or lymphatic malformations. Fast, or high-flow lesions include an arterial component, and are categorized as arteriovenous malformations. IH and CVMs are among the most common benign vascular lesions seen and treated in dermatology. CVMs are present at birth and grow as the individual does, whereas IH usually appear days to weeks later and may rapidly enlarge for a period of months to a year before gradually involuting. As the technology has evolved, early and often laser treatment with the pulsed dye 595-nm laser has become our standard therapy of choice. More recently, we have started more patients on combination therapy for IH with the topical beta blocker timolol. If left untreated, CVMs darken and thicken, making them increasingly difficult to successfully treat with lasers. IH involute, sometimes resulting in fibrofatty, atrophic plaques. These individuals can undergo ablative fractional resurfacing with a fractional CO2 laser to improve the texture and appearance of these lesions.

Terminal Deletion 2q37.3 in a Patient with Klippel-Trenaunay-Weber Syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder, characterized by capillary, venous and lymphatic vascular malformations in association with bone and soft tissue hypertrophy. We report a KTWS patient with extensive hemangiomatosis of the right lower limb, trunk and upper limbs; bone and soft tissue hypertrophy of upper limbs, scapular girdle and right lower limb; and muscle atrophy on left lower limb with marked body asymmetry, scoliosis and toe malformations. These pathological features are associated with moderate mental retardation, mild renal and hepatic abnormalities. We identified by array CGH (Comparative Genomic Hybridization) a submicroscopic deletion 2q37.3 that could be related to impaired cognitive function. To our knowledge this is the first reported 2q37.3 microdeletion in a patient with KTWS.