Cutaneous Capillary Malformations Research Articles

Klippel-Trénaunay Syndrome and Angiokeratoma: Case Report of a Rare Condition

Introduction: Klippel-Trénaunay syndrome is a rare congenital vascular disorder characterized by a triad of cutaneous capillary malformations, varicosities and hypertrophy of soft tissues and overgrowth bones. Among the cutaneous malformations are angiokeratomas, which appear as a papule from 2 to 10 mm in diameter, usually dark red in color, although they may be blue or black, and their surface is keratotic on palpation. Angiokeratomas pose a therapeutic challenge, especially in cases of multiple or extensive lesions. Laser modalities have demonstrated efficacy and may be successful treatment options. Clinical Case: A 13-year-old male patient with a clinical history of Klippel-Trénaunay syndrome diagnosed at birth. He came to the outpatient services because he presented dermal nodular lesions at the inguinal region, painful on palpation, with a duration of one week. In addition, he had an increase in diameter of the left lower limb with multiple varicose veins, ochre dermatitis on the inner side of his left leg. On the right lower limb there are violaceous patches with the presence of euchromic papules grouped together, of hard consistency at the left knee region. He also presents multiple violaceous keratotic papules on the scrotum, thigh and left knee bleeding on manipulation and trauma. Skin excision was performed in the right inguinal region for biopsy, which reported macroscopically fibrous, multinodular element measuring 0.7x0.5x0.3cm, whitish surface of firm consistency and whitish heterogeneous surface upon sectioning. Microscopic inspection was carried out with hematoxylin and eosin technique, which reported skin with epidermis showing acanthosis, hyperkeratosis, papillary dermis with congestive dilated vessels, negative for malignancy and compatible with angiokeratoma. Among the treatment options, it was decided to initiate CO2 laser therapy with satisfactory results. Conclusions: Klippel-Trénaunay syndrome is an extremely rare vascular pathology ........

Sturge-Weber syndrome: an update for the pediatrician.

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by the simultaneous presence of both cutaneous and extracutaneous capillary malformations. SWS usually presents as a facial port-wine birthmark, with a varying presence of leptomeningeal capillary malformations and ocular vascular abnormalities. The latter may lead to significant neurological and ocular morbidity such as epilepsy and glaucoma. SWS is most often caused by a somatic mutation involving the G protein subunit alpha Q or G protein subunit alpha 11 gene causing various alterations in downstream signaling pathways. We specifically conducted a comprehensive review focusing on the current knowledge of clinical practices, the latest pathophysiological insights, and the potential novel therapeutic avenues they provide. A narrative, non-systematic review of the literature was conducted, combining expert opinion with a balanced review of the available literature. A search of PubMed, Google Scholar and Embase was conducted, using keywords "Sturge-Weber Syndrome" OR "SWS", "Capillary malformations", "G protein subunit alpha 11" OR "G protein subunit alpha Q". One of the hallmark features of SWS is the presence of a port-wine birthmarkat birth, andforehead involvement is most indicative for SWS. The most common ocular manifestations of SWS areglaucoma andchoroidal hemangioma.Glaucomapresentsin either in infancy (0-3years of age) or later in life.Neurological complications are common in SWS, occurring in about 70%-80% of patients, with seizures being the most common one.SWS significantly impacts the quality of life for patients and their families, and requires a multidisciplinary approach for diagnosis and treatment. Currently, no disease-modifying therapies exist, andtreatment is mostly focused on symptoms or complications as they arise. CONCLUSIONS: SWS remains a complex and heterogeneous disorder. Further research is needed to optimize diagnostic and therapeutic strategies, and to translate insights from molecular pathogenesis to clinical practice.

A Neonate Diagnosed with Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome with PIK3CA Mutation

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare genetic disorder characterized by megalencephaly, polymicrogyria, body overgrowth, and cutaneous capillary malformations. It has been reported recently that MCAP is related to a somatic mosaic mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (<i>PIK3CA</i>) gene. We report a case of hemimegalencephaly with polymicrogyria and cutaneous capillary malformations diagnosed by genetic evaluation of MCAP in the neonatal period. The <i>PIK3CA</i> mutation [c.1635G>T (p. Glu545Asp)] was determined by Sanger sequencing. The patient was treated with a ventriculoperitoneal shunt for progressive hydrocephalus. Because of the dynamic, progressive clinical manifestations and tumor-prone traits of MCAP, early diagnosis is important. Moreover, since the phosphoinositide 3-kinase (PI3K)-specific inhibitor, a targeted therapy for the PI3K/AKT/mTOR signaling pathway is emerging as a new therapy, early genetic diagnosis is becoming increasingly important.

Mapping port wine stain in vivo by optical coherence tomography angiography and multi-metric characterization.

Port wine stain (PWS) is a congenital cutaneous capillary malformation composed of ecstatic vessels, while the microstructure of these vessels remains largely unknown. Optical coherence tomography angiography (OCTA) serves as a non-invasive, label-free and high-resolution tool to visualize the 3D tissue microvasculature. However, even as the 3D vessel images of PWS become readily accessible, quantitative analysis algorithms for their organization have mainly remained limited to analysis of 2D images. Especially, 3D orientations of vasculature in PWS have not yet been resolved at a voxel-wise basis. In this study, we employed the inverse signal-to-noise ratio (iSNR)-decorrelation (D) OCTA (ID-OCTA) to acquire 3D blood vessel images in vivo from PWS patients, and used the mean-subtraction method for de-shadowing to correct the tail artifacts. We developed algorithms which mapped blood vessels in spatial-angular hyperspace in a 3D context, and obtained orientation-derived metrics including directional variance and waviness for the characterization of vessel alignment and crimping level, respectively. Combining with thickness and local density measures, our method served as a multi-parametric analysis platform which covered a variety of morphological and organizational characteristics at a voxel-wise basis. We found that blood vessels were thicker, denser and less aligned in lesion skin in contrast to normal skin (symmetrical parts of skin lesions on the cheek), and complementary insights from these metrics led to a classification accuracy of ∼90% in identifying PWS. An improvement in sensitivity of 3D analysis was validated over 2D analysis. Our imaging and analysis system provides a clear picture of the microstructure of blood vessels within PWS tissues, which leads to a better understanding of this capillary malformation disease and facilitates improvements in diagnosis and treatment of PWS.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension concomitant with Klippel–Trenaunay–Weber syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder characterized by cutaneous capillary malformations, bone hypertrophy, and multiple venous or lymphatic malformations. KTWS is associated with chronic thromboembolic pulmonary hypertension (CTEPH), presumably due to thromboembolism from multiple vascular malformations. Here, we report the first case series of patients with KTWS-CTEPH who underwent balloon pulmonary angioplasty (BPA). Both patients are alive 20 years and 1 year after the initial diagnosis of CTEPH, respectively, and are stable with improved hemodynamics. BPA may be an effective treatment option for patients with KTWS-CTEPH.

Early-onset hypertension associated with extensive cutaneous capillary malformations harboring postzygotic variants in GNAQ and GNA11.

Cutaneous capillary malformations (CMs) describe a group of vascular birthmarks with heterogeneous presentations. CMs may present as an isolated finding or with other associations, including glaucoma and leptomeningeal angiomatosis (i.e., Sturge-Weber syndrome) or pigmentary birthmarks (i.e., phakomatosis pigmentovascularis). The use of targeted genetic sequencing has revealed that postzygotic somatic variations in GNAQ and GNA11 at codon 183 are associated with CMs. We report five patients with early-onset hypertension and discuss possible pathogenesis of hypertension. Twenty-nine patients with CMs, confirmed GNAQ/11 postzygotic variants, and documented past medical history were identified from a multi-institutional vascular anomalies study. Early-onset hypertension was defined as hypertension before the age of 55 years. Clinical data were reviewed for evidence of hypertension, such as documentation of diagnosis or elevated blood pressure measurements. Five of the 29 patients identified as having GNAQ/11 postzygotic variants had documented early-onset hypertension. Three individuals harbored a GNAQ p.R183Q variant, and two individuals harbored a GNA11 p.R183C variant. All individuals had extensive cutaneous CMs involving the trunk and covering 9%-56% of their body surface area. The median age of hypertension diagnosis was 15 years (range 11-24 years), with three individuals having renal abnormalities on imaging. Early-onset hypertension is associated with extensive CMs harboring somatic variations in GNAQ/11. Here, we expand on the GNAQ/11 phenotype and hypothesize potential mechanisms driving hypertension. We recommend serial blood pressure measurements in patients with extensive CMs on the trunk and extremities to screen for early-onset hypertension.

Capillary Malformation - Arteriovenous Malformation Type 2: Case Report and Review.

Capillary malformation - Arteriovenous malformation syndrome (CM-AVM) is a rare genodermatosis with cutaneous capillary malformations (CMs) and a risk of associated fast-flow malformations. A four-generation family with a novel heterozygous pathogenic variant in the EPHB4-gene (NM_004444.5 (EPHB4): c.2224G>C, p.(Ala742Pro)) is presented. Based on a review of literature we retrieved 127 CM-AVM2 patients with confirmed variants in EPHB4. Multiple CMs were present in 114 (89,76 %) patients and 12 (9,44 %) patients had a solitary CM. arteriovenous malformations/fistulas were present in 23 (18,1 %) patients and located within CNS in five (3,9 %) patients. Not all included papers included description of epistaxis. Telangiectasias were reported in 28 (22 %) patients and Bier spots described in 20 (15,7 %) patients. The clinical characteristics of CM-AVM2 are diverse and often discrete which makes it difficult to distinguish CM-AVM2 from HHT.

Proteus Syndrome: A Rare Case in An Adult Ward.

Proteus syndrome is an extremely rare disorder that manifests as an asymmetric, disproportionate overgrowth of any connective tissue.The diagnosis can be difficult because the phenotypes are variable.It is important to keep in mind the importance of anticoagulation because patients are at risk of developing deep vein thrombosis and pulmonary embolism.

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

1544 Klippel-Trenaunay-Weber: Rare Congenital Syndrome Causing Persistent Rectal Bleeding

INTRODUCTION: Klippel-Trenaunay Weber syndrome (KTS) is a rare congenital disorder characterized by a triad of cutaneous capillary malformation (port-wine stain), venous malformations and limb hypertrophy. Diffuse vascular malformations of the gut in KTS can lead to gastrointestinal (GI) bleeding ranging from minor to life threatening hemorrhage necessitating surgical intervention. We describe a case of persistent rectal bleeding and iron dependent anemia in a patient with KTS. CASE DESCRIPTION/METHODS: A 32-year-old female with previous diagnosis of KTS was seen for recurrent hematochezia and iron deficiency anemia. A recent colonoscopy demonstrated non-bleeding arteriovenous malformations (Figure 1), presumed to be the source for the recurrent rectal bleeding episodes. On exam, she appeared pale, had a right hip deep purple telangiectasia, right posterior thigh palpable mass without visible varicosities and no limb hypertrophy. Her laboratory tests revealed: Hb: 9 g/dl, mean corpuscular volume: 75.0 fl, ferritin: 3 ng/ml and serum iron: 22 mcg/dl. CT abdomen/pelvis showed diffuse thickening of the rectum and sigmoid colon with scattered mural calcifications. A repeat colonoscopy demonstrated non-bleeding large circumferential vascular malformation extending from the dentate line to about 20 cm in the rectum (Figure 2) and multiple soft, pale lymphatic blebs in the colon and rectum (Figure 3). Her iron deficiency anemia from chronic blood loss was treated with oral and IV iron therapy. Despite conservative therapy, patient continues to bleed intermittently but has decided against surgical intervention at this time. DISCUSSION: GI hemorrhage occurring in association with KTS is an uncommon cause of rectal bleeding but is the most common symptom and potentially life-threatening emergency of KTS involving the gut. Investigation should begin with visualization of the entire GI tract for localization and extension of the disease. Angiography remains the gold standard and carries the advantage of allowing therapeutic interventions to control bleeding. The management of GI vascular malformations in KTS depends on the frequency and severity of blood loss requiring transfusions. Conservative management and iron supplements may be sufficient in the patient who presents with occasional non-debilitating bleeding. Transfusion dependency and life-threatening bleeding episodes necessitate definitive surgical therapy which involves resection of the diseased bowel.

LASER SURGERY FOR CUTANEOUS SIMPLE CAPILLARY MALFORMATIONS IN CHILDREN

There are presented data on the epidemiology, pathogenesis, and diagnosis of cutaneous simple capillary malformations, described as Nevus simplex and Nevus flammeus (NF) in the Classification of Vascular Anomalies in a revision on May 2108. There are compared the efficacy and side effects of an application of laser irradiation of different wavelengths for the laser surgical treatment of NF in patients of various ages. There are described features of morphometry and angioarchitecture of the vascular bed of NF at the early and advanced stages of the disease. In order to substantiate the choice of the preferred laser irradiation settings, the peculiarities of absorption of the laser irradiation with different wavelengths by main cutaneous photothermophores (chromophores) are compared in children of various ages. For the first time, there are presented data on the age-related features of the absorption coefficient and the relevant absorption index for laser irradiation of different wavelengths. The maximum values of the absorption coefficients and the index of the relevance of the absorption of laser radiation with a wavelength of 578 nm by the main skin photothermophores indicate the greatest efficiency of the domestic copper vapor laser for the surgical treatment of NF in children of different ages.

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum–maximum 26–50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Mutation ephb4 responsable de malformation anévrysmale de la veine de Galien

Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all pediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients who presented this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of EPHB4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, wich is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild type but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation–arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

Klippel-Trenaunay Weber syndrome

Klippel–Trenaunay–Weber syndrome (KTWS) is a rare congenital malformation, characterized by constellation of arteriovenous malformation, cutaneous capillary malformation, and skeletal or soft-tissue hypertrophy. The exact cause of KTWS is unknown. We present a case of a 1 ½-year-old boy with multiple swellings over the right lower extremity since birth which increased in size in proportion to his general growth. He was diagnosed clinically as Klippel–Trenaunay syndrome (KTS) which on Doppler imaging and on histopathology showed the presence of a multichanneled slow-flowing arteriovenous malformation. KTWS should be distinguished from KTS since clinical features, management, and prognosis of these two entities are distinctly different. Although the diagnosis is primarily clinical, confirmation requires laboratory and imaging studies. The present case is being reported as an interesting case which highlights the fact that distinction between KTWS and KTS may sometimes be difficult.

Periodontal Manifestations and Unusual Radiographic Features in a Patient with Sturge-Weber Syndrome: A Case Report

The Sturge-Weber syndrome or encephalotrigeminal angiomatosis is a rare neurological and congenital disorder with a frequency of 1 in 50,000 births. This syndrome is a nonhereditary developmental condition and is characterized by the presence of congenital capillary malformation and a hamartomatous vascular proliferation involving the face (port-wine stain or facial birthmark), sometimes skull and the tissues of brain, jaws, oral soft and hard tissues and rarely other body organs. Seizures, mental retardation, and cortical calcification (tram-tracks) and congenital glaucoma may be seen in this syndrome. We report here a 40-year-old female with Sturge-Weber syndrome associated with bilateral cutaneous capillary malformation on her face, neck, hands and feet and also gingival enlargement.

Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report.

IntroductionKlippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues.AimsTo report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome.MethodsOn presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report.ResultsA 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months.ConclusionThis case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further.Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180–183.

Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation.

See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

A case of disseminated intravascular coagulation developed after surgical management of corpus luteal hemorrhage in a patient with Klippel-Trenaunay syndrome

Klippel-Trenaunay syndrome (KTS) is a complex congenital disorder characterized by a triad of varicose veins, cutaneous capillary malformation, and hypertrophy of bone and/or soft tissue. KTS may be associated with massive hemorrhage or coagulopathy that be a life-threatening situation. Although women in reproductive age are at risk of ruptured corpus luteum with active arterial bleeding, if it managed properly, the development of serious complications, such as disseminated intravascular coagulation (DIC) rarely develops. However, in case of patient with vascular malformation, there is possibility of unexpected complication occurrence such as DIC. The authors report a case of a 29-year-old female with KTS who presented with corpus luteal hemorrhage and which lead to DIC, despite adequate surgical and medical treatment.

First report of microcephaly-capillary malformations syndrome in Russia

BackgroundMicrocephaly-capillary malformation (MIC-CAP) syndrome is a newly described autosomal recessive syndrome characterized by microcephaly, multiple cutaneous capillary malformations, intractable epilepsy and profound developmental delay. We present the first description of MIC-CAP syndrome in Russia. PatientWe describe a 6-month-old girl with severe congenital microcephaly, intractable epilepsy (infantile spasms), multiple cutaneous capillary malformations and facial abnormalities. Genetic studies revealed the presence of new STAMPB gene mutations in the compound heterozygous state: c.273delA and the intron replacement c.204-5 C>G. ConclusionsThis report presents a case of MIC-CAP syndrome with earlier unreported new mutations of the STAMPB gene.

Prospective pilot study on combined use of pulsed dye laser and 1% topical rapamycin for treatment of nonfacial cutaneous capillary malformation

Background: The regeneration or revascularization of blood vessels after pulsed dye laser (PDL) treatment is one of the causes of treatment failures of cutaneous capillary malformations (CM). Recently, topical administration of rapamycin was introduced as a possible adjunctive therapeutic option to minimize postlaser revascularization in facial CM.Objectives: We evaluated the effect of combined use of 1% topical rapamycin with PDL compared to PDL alone in cutaneous CM of trunk or extremities and tried to identify the optimal duration of topical rapamycin application.Methods: Three adjacent areas of cutaneous CM that had never been treated before were selected in each patient and underwent the following regimens: (A) PDL + vehicle for 8 weeks post-PDL; (B) PDL + topical rapamycin for 1-week post-PDL and (C) PDL + topical rapamycin for 8 weeks post-PDL. Each test site was treated by PDL for two sessions with 8 weeks interval.Results: Only one of six patients showed clinical improvement with combined rapamycin treatment. Overall, there was no statistically significant difference in erythema and blanching rate among PDL alone and combined rapamycin regimens.Conclusion: One percent topical rapamycin does not seem to be effective as a treatment modality for cutaneous CM of trunk or extremities.