Lower socioeconomic status is associated with delayed access to care for infantile hemangioma: A cohort study.

BACKGROUND: Early specialist evaluation during rapid proliferative growth of complicated infantile hemangiomas (IHs) is crucial. Health disparities and barriers of access to care for children with IHs have not been examined. OBJECTIVE: To investigate whether socioeconomic status (SES) is associated with age at presentation to a subspecialist for IH evaluation. METHOD: A retrospective cohort study of 804 children presenting to a large academic hospital. The primary outcome was age at initial presentation. Covariates included demographic, socioeconomic, geographic, and clinical characteristics. Medicaid and the Children's Health Insurance Program were proxies for lower SES. Analysis of covariance, chi-square tests, and generalized ordered logistic regressions were performed. RESULTS: Children with lower SES had higher odds of presenting after 3 months of age (odds ratio, 2.11; 95% confidence interval, 1.31-3.38). In the subset that qualified for the institutional care management program (ICMP), no risk factors were associated with delayed presentation. LIMITATIONS: Use of insurance and economic distress as proxies for SES; exclusion of uninsured children, which may have resulted in underestimation of racioethnic effects; and examination of a single academic center, which may limit generalizability. CONCLUSIONS: Children with IHs and lower SES were more likely to present later to specialists, but those enrolled in an ICMP were not, suggesting that integrated ICMPs may mitigate disparities and delayed access to care for IHs among lower-SES populations.

Incidence and clinical factors associated with ulceration in infantile hemangiomas.

BACKGROUND: Ulceration is an important complication in infantile hemangiomas (IHs). Prior to the use of ß-blockers, the estimated incidence of this complication in a referral population was between 15% and 30%. The incidence and factors associated with ulceration have not been systematically studied since the emergence of ß-blocker therapy. OBJECTIVE: Examine the incidence and clinical predictors for ulceration in IHs. METHODS: Retrospective study at tertiary referral centers. RESULTS: Compared with a previous large pre-propranolol cohort study, ulceration occurred at a significantly lower incidence of 11.4%. Clinical factors associated with ulceration included partial segmental morphology, location in the diaper area, and size greater than 5 cm. Higher risk of ulceration in Black patients was observed, suggesting barriers to care including delayed diagnosis and referral to specialty care. LIMITATIONS: Retrospective design at tertiary referral centers. CONCLUSION: Compared with reports before the use of ß-blockers became widespread, the incidence of ulceration in IHs has decreased. However, it continues to be a relatively frequent complication of IH.

Anatomic Distribution of Cherry Angiomas in the General Population.

BACKGROUND: Cherry angiomas are common benign vascular skin lesions of unknown aetiology, found largely on the trunk. However, their exact anatomic distribution besides their truncal predisposition, and how they manifest in the general population, has not been characterised. METHODS: Three-dimensional (3D) total body imaging was obtained from 163 adult participants of a general population cohort study in Brisbane, Australia. Demographic, phenotypic, and sun behaviour characteristics were collected using a standard questionnaire along with history of melanoma and keratinocyte cancers. Cherry angiomas were identified using an automated classification algorithm with a sensitivity of 87% and a specificity of 99%, developed specifically for this study population. RESULTS: The 3D total body images of 163 participants were analysed. Participants had a median age of 57 years and 61% were male. On average, males had more angiomas than females (median of 16 vs. 12) and the number and size of cherry angiomas increased with age. In addition to male sex and age, an increase in angiomas was associated with Caucasian ancestry other than British/Irish only, fair skin colour opposed to medium/olive, having green/hazel eyes compared to blue/grey, and personal history of melanoma. The most common site for cherry angiomas was the front trunk, followed by the back. Interestingly, although males had more angiomas overall, females had more angiomas on the legs. CONCLUSION: Describing the distribution of cherry angiomas by body site is an important step towards further understanding of the aetiology of angiomas. While personal history of melanoma is associated with an increased number of cherry angiomas, whether this association is prognostic, co-occurs with development of melanoma, or is merely fortuitous requires further investigation.

Intracranial capillary hemangiomas: literature review in pediatric and adult population.

Capillary hemangiomas (CHs) of the central nervous system represent a rare diagnosed pathology. CHs are benign vascular tumors whose most common manifestations are dermal and mucous and mainly occur during childhood or adolescence, while the involvement of the central nervous system can occur in a wider age range. We conducted a PubMed research on literature published until March 2020. We only enrolled cases with histological documented presence of intracranial CH. For every case collected, we analyzed age, sex, localization, neuroimaging studies performed, the presence of extracranial CHs, symptoms, neurological deficits, extent of surgical resection (biopsy, partial or gross total), adjunct treatment received (radiotherapy, chemotherapy, Trans-Arterial Embolization TAE), and outcome. Up to March 2020, the literature review identified 52 cases to which we added the case of our personal experience. The mean age was 26 with slightly female prevalence (28 F, 25 M). The most common presenting symptom was headache (21 cases, 40%). The surgical treatment consisted of biopsy in 7 cases (13%), partial resection in 10 cases (19%), gross total resection in 31 cases (58.5%), biopsy followed by total resection in 2 cases (3%), and partial resection followed by total resection in 1 case (1.5%), and the diagnosis was obtained from an autopsy sample in 1 case (1.5%). For symptomatic lesions, surgery is a valid option to obtain histological characterization, neurological improvement, and where possible a total resection. Stereotactic radiotherapy can be used if the lesion is not surgically approachable or as an adjuvant treatment in case of partial resection, having shown good results in terms of long-term disease control.

Persistent Nasal Infantile Hemangioma: A Surgical Treatment Algorithm.

Treatment of infantile hemangioma is usually medical. The nose is one of the most important aesthetic and functional units of the face; therefore, surgical management is preferred in persistent lesions (fibro-fatty tissue component) that do not respond to medical treatment. Herein, the authors analyze the results of surgical nasal hemangioma treatment in their center, a literature review and propose an algorithm for surgical management. A retrospective analysis of 23 persistent nasal hemangioma operated between 1996 and 2014 at our institution was made. The authors recollected the following demographic and clinical data: hemangioma subtype, phase of evolution, affected aesthetic nasal subunit, previous treatment, surgery type, complications and follow-up period. The Strasser scale was chosen for assessment of postoperative photographic results. Surgical treatment was performed. Age average was 6.8 years old (range 2-19). Mixed hemangioma was the most common subtype (83%). Surgery was mainly performed in the involution phase (87%). The most affected aesthetic subunit was nasal tip (44%). All lesions received previous medical treatment. The most common surgical technique was open rhinoplasty approach. Follow-up was an average of 26.6 months. Aesthetic results according to the Strasser method included: 3 excellent scores, 15 good, 5 regular, and none poor. Surgery was performed on patients in order to correct nasal persistent hemangiomas sequel. The nose has serious psychosocial impact and mixed infantile hemangiomas appear to have a higher rate of persistent hemangioma requiring surgery, but further studies are needed. Aesthetic outcome with surgical procedures chosen were acceptable and no complications were reported.

Clinical features and treatment outcomes of vasoproliferative tumors in Indian participants.

PURPOSE: The aim of the study was to describe the clinical features and treatment outcomes of vasoproliferative tumors (VPT) in Indian participants. METHODS: This study design was a retrospective case series in a tertiary eye care center. Case records of patients diagnosed with VPT from 2011 to 2015 were reviewed, and their demographic details, clinical presentation, and treatment outcomes were documented. Baseline and follow-up visual acuity and tumor dimensions were statistically compared by applying paired t-test. Statistical analysis used SPSS version 14. RESULTS: Twenty-two tumors from 19 eyes of 17 patients were included. Mean age at presentation was 43.5 years (range: 15-68 years). Mean presenting best-corrected visual acuity (BCVA) was + 1.10 logMAR. Sixty-eight percent eyes had secondary tumors. Most common association of secondary VPT was Coats disease followed by retinal vasculitis, polypoidal choroidal vasculopathy, familial exudative vitreoretinopathy, and traumatic chorioretinopathy. Ten tumors (45%) involved the inferior quadrant. Tumor-associated features were intra/subretinal exudates, vitritis, subretinal fluid, vitreous hemorrhage, preretinal fibrosis, epiretinal membrane, and subretinal blood. Treatment included cryotherapy, intravitreal or oral steroids, laser photocoagulation, cryotherapy with encirclage, cryotherapy with anti-vascular endothelial growth factor, and observation. Complications included tumor recurrence, retinal detachment, raised intraocular pressure, neovascularization of iris, and cataract. Ninety-five percent VPT regressed at mean 21 months (Median: 17 months; Range: 3-64 months). Mean final BCVA was + 1.21 logMAR. CONCLUSION: VPTs are commonly unilateral, unifocal, and located anterior to equator in inferior fundus. Secondary tumors are more common than primary tumors. Treatment achieves tumor regression in majority of cases.

Use of the Hemangioma Severity Scale to facilitate treatment decisions for infantile hemangiomas.

BACKGROUND: The Hemangioma Severity Scale (HSS) assesses the severity of an infantile hemangioma (IH). OBJECTIVE: First, to compare HSS scores between patients with IH for whom propranolol treatment was indicated at their first visit and those who were not treated. Second, to assess suitable cutoff values for the need for propranolol treatment. METHOD: All patients with IH who attended our tertiary referral center since 2008 and were 0 to 6 months of age at their first visit were included. They were divided into propranolol and no-propranolol groups on the basis of choice of treatment at their first visit. HSS scores were assessed, and median scores were compared. RESULTS: A total of 657 children (342 in the propranolol group) were included. The median HSS score (25th-75th percentile) in the propranolol group was 10 (range, 8-14) compared with 7 (range, 4-9) in the no-propranolol group (P < .001). Cutoff values of 6 or lower (no indication for treatment) and 11 or higher (indication for treatment) resulted in 94% sensitivity and 89% specificity, respectively. LIMITATIONS: HSS scoring was not completely blinded. CONCLUSION: The HSS with cutoff values of 6 or lower and 11 or higher could be used as a triage tool for propranolol treatment. Patient age, IH type, and parental preference may also contribute to treatment decisions.

Inheritance Patterns of Infantile Hemangioma.

BACKGROUND AND OBJECTIVE: Infantile hemangioma (IH) includes, among its other risk factors, familial clustering, but a definitive understanding of IH's inheritance model and genetic basis is lacking. Our objective was to collect IH pedigrees in Finland, to study the inheritance patterns of IH within these families, and to analyze the characteristics of familial IHs. METHODS: We identified 185 patients with IH who visited our vascular anomaly clinic between 2004 and 2007. Based on hospital records and a questionnaire sent to these patients and their families, IH characteristics and family history of IH were studied. We compared characteristics between patients with positive (familial) and negative (sporadic) IH family history. Families with positive IH family history were further interviewed for extended pedigree data. RESULTS: One-third of our IH cohort's families reported a family history positive for IH, with IH characteristics and perinatal data between the familial and sporadic cases being similar. IH patients with affected first-degree relatives reported higher long-term discomfort rates than the sporadic cases. Of the 40 families interviewed, 11 included ≥4 IH-affected family members; these were most commonly first-degree relatives (63%). Segregation patterns match with autosomal dominant inheritance with an incomplete penetrance or maternal transmission. We also present a case of monozygotic twins that manifest identical IHs. CONCLUSIONS: Based on this large number of IH pedigrees, we suggest at least 2 possible mechanisms of inheritance: autosomal dominant and maternal transmission. This study highlights the need for additional genetic studies to define inheritance of this common disease.

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

Human herpesvirus 8 (HHV8) has been hypothesized to be a potential cofactor for the development of diverse cutaneous vascular proliferative lesions, including eruptive cherry angiomas. Recent reports evidenced the influence of killer cell immunoglobulin-like receptor (KIR) gene diversity in defining the susceptibility to symptomatic herpesvirus infections. In this study, skin samples from vascular lesions and healthy controls were characterized simultaneously for the presence of HHV8 and for the KIR genotype, focusing upon the presence of the KIR2DL2/DS2 and KIR2DL3 genes, which have been associated to herpesvirus susceptibility. The results showed that about 64 % of the vascular lesions resulted positive for the presence of HHV8, whereas no control healthy skin samples harbored HHV8 DNA. HHV8-positive patients had a significantly increased frequency of KIR2DL2/DS2 homozigosity and a concomitant decrease of the homozygous KIR2DL3 genotype, compared to healthy controls or HHV8-negative patients. Notably, the simultaneous presence of KIR2DL2/DS2 homozygosity and HHV8 infection resulted in a significantly increased risk to develop cutaneous lesions (OR 5.7) compared to the individual factors alone, suggesting that specific KIR genotypes might predispose to HHV8 symptomatic infection, allowing the virus to exert its angioproliferative activity at skin level.

Anatomical patterns of infantile hemangioma (IH) of the extremities (IHE).

BACKGROUND: From 18% to 30% of infantile hemangiomas (IH) are located on the extremities (IHE). They can be divided into localized, segmental, and minimal or arrested growth (IH-MAG) subtypes. OBJECTIVE: We sought to correlate localization of IHE with the anatomy of the arterial vascular supply. METHODS: All children with segmental IHE and IH-MAG presenting to our department of pediatric dermatology from 2002 to 2015 were evaluated. Hemangiomas were mapped and their patterns were analyzed. RESULTS: Most IHE were unilateral (105/109). Two thirds (68/109) were located on the upper, and one third (41/109) on the lower extremities. Distal locations were more frequently affected. Segmental IHE were more common (upper extremities 83.8%; lower extremities 56.1%) than IH-MAG (16.2% and 43.9%, respectively). Ulceration occurred in 5.5%. Localization of IHE was found to correspond to supply areas of embryonic arterial variants. LIMITATIONS: This was a retrospective study. Only segmental IHE and IH-MAG were evaluated. Angiographic studies were not performed. CONCLUSION: The location of IHE may be related to variant anatomy of arterial supply during embryo fetal development. We hypothesize that this contributes to temporary regional tissue hypoxia during early fetal development, which is a known stimulus for the proliferation of hemangioma stem cells.

Increasing incidence of infantile hemangiomas (IH) over the past 35 years: Correlation with decreasing gestational age at birth and birth weight.

BACKGROUND: Infantile hemangiomas (IH) are the most common soft-tissue tumors of infancy, but little is known regarding their true incidence. OBJECTIVES: We sought to determine the current incidence of IH and examine trends in incidence, demographics, and lesion characteristics over 3 decades. METHODS: The Rochester Epidemiology Project was used to identify infants residing in Olmsted County, Minnesota, who were given a diagnosis of IH between January 1, 1976, and December 31, 2010. RESULTS: In all, 999 infants were given a diagnosis of IH. Incidence increased over the 3-decade study period from 0.97 to 1.97 per 100 person-years (P < .001). Average gestational age at birth and birth weight for infants with IH decreased over the study period (39.2-38.3 weeks, P < .001 and 3383-3185 g, P = .003, respectively). The overall age- and sex-adjusted incidence of IH was 1.64 per 100 person-years (95% confidence interval 1.54-1.75). LIMITATIONS: The population of Olmsted County, Minnesota, is predominantly non-Hispanic white, limiting our ability to report racial differences in incidence. This was a retrospective study. CONCLUSIONS: This study provides a longitudinal, population-based incidence of IH. Incidence has increased steadily over the past 3 decades, correlating significantly with decreasing gestational age at birth and birth weight in affected infants.

Impact of Screening for Hepatic Hemangiomas in Patients with Multiple Cutaneous Infantile Hemangiomas.

OBJECTIVES: Hepatic hemangiomas are often found in association with multiple cutaneous infantile hemangiomas. Screening abdominal ultrasonography has been recommended for patients with five or more cutaneous lesions. We sought to determine whether hemangiomas found through screening had improved clinical outcomes. METHODS: Patients entered into our hepatic hemangioma registry between 1995 and 2012 were reviewed. RESULTS: Seventy-two patients with multiple cutaneous and hepatic hemangiomas were identified; 43 (60%) were detected through screening. The median age at diagnosis was 41 days for screened patients and 53 days for those not screened. Screening detected 40 (93%) multifocal and 3 (7%) diffuse hemangiomas, compared to 18 (62%) and 11 (38%), respectively, in the nonscreened group. Patients identified by screening had lower incidences of congestive heart failure and hypothyroidism and were less likely to receive treatment for their hemangiomas. The mortality rate in the children not screened was 28% (n = 8). None of the patients found by screening died (p < 0.001). Multivariate analysis of treated patients demonstrated that screening was a significant predictor of reduced mortality (p = 0.04). CONCLUSION: Hepatic hemangiomas found through screening ultrasonography are less likely to develop serious clinical sequelae. Although the reasons for this may include detection of hemangiomas that are less likely to progress to symptomatic disease, it appears that it also allows for earlier intervention for more concerning (e.g. diffuse) subtypes. Screening may allow for closer surveillance and earlier treatment before life-threatening progression in a subset of infants with liver hemangiomas, preventing complications and reducing mortality.

Hemangiomas and the eye.

Infantile hemangiomas are a common vascular birthmark with heterogeneous presentations and unique growth characteristics with early rapid growth and eventual self-involution. Hemangiomas that develop around the eye have the potential for inducing amblyopia by several mechanisms and may eventually result in permanent visual impairment in otherwise healthy infants. Segmental periocular hemangiomas carry the additional risk of associated structural anomalies and PHACE syndrome. In recent years, the treatment of periocular hemangiomas has been revolutionized by the serendipitous discovery of the effectiveness of beta-blockers (systemic and topical), with most experts viewing these as first-line therapies. The management of periocular hemangiomas should involve a close partnership between an ophthalmologist and dermatologist or other relevant specialists familiar with the unique clinical features, differential diagnosis, treatment approaches, and potential complications.

Maternal and Perinatal Factors of Importance for Occurrence and Severity of Infantile Haemangioma.

To determine which patient and maternal factors are associated with the occurrence and the severity of infantile haemangioma (IH), a single-centre retrospective observational study was conducted with 96 haemangioma patients and 143 age-matched control babies, born in the same hospital between March 2012 and March 2013. The IH patients were selected according to diagnosis from dermatologists, either consulted from the department of paediatrics or in outpatient setting. Unplanned female children whose mothers smoked and/or consumed alcohol when pregnant was more likely to have IH (p < 0.0.05). The higher the birth weight, the more superficial the haemangioma (p = 0.023), and localised lesions were more common in singleton babies (p = 0.023) and babies conceived by normal fertilisation (p = 0.002). The occurrence and severity of IH is not only influenced by patient factors but also by maternal factors especially care during pregnancy period. By controlling these factors, the incidence and severity of IH may be lowered.

Intramuscular capillary-type hemangioma: radiologic-pathologic correlation.

BACKGROUND: Infantile hemangiomas demonstrate a pattern of proliferative growth in infancy followed by a slow phase of involution. In contrast a rare type of vascular tumor, intramuscular capillary-type hemangioma, usually presents beyond the period of infancy with nonspecific symptoms and no evidence of involution. OBJECTIVE: The purpose of this study was to characterize the clinical, imaging, histopathological characteristics and management of intramuscular capillary-type hemangioma. MATERIALS AND METHODS: We performed a retrospective review of a 20-year period to identify children diagnosed with intramuscular capillary-type hemangioma. Patient demographics, imaging and histopathological findings were recorded. RESULTS: We included 18 children (10 boys, 8 girls) with histologically proven intramuscular capillary-type hemangioma - and adequate imaging. The mean age at presentation was 8.1 years (range 1 day to 19 years). Twelve lesions involved muscles of the extremities, 4 were located in the trunk and 2 were in the head and neck. MRI had been performed in all children and demonstrated a soft-tissue mass with flow voids, consistent with fast flow. The lesion was well-circumscribed in 16 children and intralesional fat was seen in 14. Doppler US demonstrated a heterogeneous lesion, predominantly isoechoic to surrounding muscle, with enlarged arterial feeders. Enlarged feeding arteries, inhomogeneous blush and lack of arteriovenous shunting were noted on angiography (n = 5). The most common histopathological findings were lobules of capillaries with plump endothelium and at least some adipose tissue. The lesions were excised in six children. Two children were lost to follow-up. In the remaining 10, follow-up MRI studies ranging from 3 months to 10 years showed that the lesion enlarged in proportion to the child (n = 7), demonstrated slow growth (n = 2) or remained stable (n = 1). There was no change in imaging characteristics on follow-up. CONCLUSION: Intramuscular capillary-type hemangioma is a rare benign vascular tumor of skeletal muscle. The most typical imaging features show a heterogeneous intramuscular mass with fast flow, and intralesional fat. Although the lesion is relatively stable in appearance over time, imaging does not obviate the need for a biopsy to rule out sarcoma. The diagnosis can usually be established by typical findings on histopathology.

Vascular tumors have increased p70 S6-kinase activation and are inhibited by topical rapamycin.

Vascular tumors are endothelial cell neoplasms whose cellular and molecular mechanisms, leading to tumor formation, are poorly understood, and current therapies have limited efficacy with significant side effects. We have investigated mechanistic (mammalian) target of rapamycin (mTOR) signaling in benign and malignant vascular tumors, and the effects of mTOR kinase inhibitor as a potential therapy for these lesions. Human vascular tumors (infantile hemangioma and angiosarcoma) were analyzed by immunohistochemical stains and western blot for the phosphorylation of p70 S6-kinase (S6K) and S6 ribosomal protein (S6), which are activated downstream of mTOR complex-1 (mTORC1). To assess the function of S6K, tumor cells with genetic knockdown of S6K were analyzed for cell proliferation and migration. The effects of topical rapamycin, an mTOR inhibitor, on mTORC1 and mTOR complex-2 (mTORC2) activities, as well as on tumor growth and migration, were determined. Vascular tumors showed increased activation of S6K and S6. Genetic knockdown of S6K resulted in reduced tumor cell proliferation and migration. Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCα, in vascular tumor cells. Rapamycin significantly reduced vascular tumor growth in vitro and in vivo. As a potential localized therapy for cutaneous vascular tumors, topically applied rapamycin effectively reduced tumor growth with limited systemic drug absorption. These findings reveal the importance of mTOR signaling pathways in benign and malignant vascular tumors. The mTOR pathway is an important therapeutic target in vascular tumors, and topical mTOR inhibitors may provide an alternative and well-tolerated therapy for the treatment of cutaneous vascular lesions.

Hemangioma of the scrotal septum: a rare entity in infants with review of the literature.

Hemagiomas are most common tumors in infancy; however, scrotal septum hemangiomas are very rare with only 45 cases reported in the literature. We report a case of a 6-month-old child who presented with a scrotal mass at birth which had increased in size with age. A scrotal ultrasound with color doppler analysis, revealed a soft tissue mass with diffusely increased blood flow. Scrotal mass excision was performed and the pathology confirmed a capillary hemangioma.