Background Skin disorders in neonates can be regarded as determining concepts for prognosis and genetic counseling. Few studies have so far been conducted on determining and recording the relative frequency of skin disorders. The present study was therefore conducted to investigate skin manifestations and their relationship with other variables in the neonates hospitalized in the neonatal intensive care unit (NICU). Methods The present cross-sectional study was conducted on 403 neonates, hospitalized in the NICU of Rasoul Akram Hospital in 2014 and selected using convenience sampling. The data collected from

Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.

No abstract

We found mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. -encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

No abstract

Juvenile hemangiomas are the most common tumors of infancy, occurring in as many as 10% of all births. These benign vascular lesions enlarge rapidly during the first year of life by hyperplasia of endothelial cells and attendant pericytes and then spontaneously involute over a period of years, leaving loose fibrofatty tissue. Several hypotheses have been put forth concerning hemangiogenesis, including the possibility that the tumor is the result of somatic mutation in one or more components of critical vascular growth-regulatory pathways. To test this hypothesis, we obtained 15 proliferative-phase hemangiomas after surgical resection and dissected them to enrich for the lesional (endothelial and pericytic) components of each specimen. To determine whether hemangiomas represent a clonal expansion from a single progenitor cell, we assayed X-inactivation patterns for each lesion by using the polymorphic X-linked human androgen receptor gene. Twelve of 14 informative hemangiomas showed a significant degree of allelic loss after methylation-based and transcription-based polymerase chain reaction clonality assays, suggesting a nonrandom X-inactivation pattern and, thus, a monoclonal origin. We then sequenced genes encoding the receptors of the vascular endothelial growth factors (VEGFs) as candidates for potential somatic mutation. Mutations were found in two of the 15 hemangioma specimens: a missense mutation (P1147S) in the kinase domain of the VEGFR2 (FLK1/KDR) gene in one specimen and a missense mutation (P954S) in the kinase insert of the VEGFR3 (FLT4) gene in another specimen. In each case, the mutation was detected in tumor tissue but not in adjacent normal tissue. These results suggest that one potential mechanism involved in hemangioma formation is the alteration of the VEGF signaling pathway in endothelial and/or pericytic cells.