Revisiting classic MRI findings of venous malformations: Changes in protocols may lead to potential misdiagnosis.

Introduction Magnetic resonance imaging (MRI) is most sensitive and specific for characterizing venous malformations (VMs). VMs typically demonstrate central enhancement on delayed-contrast imaging. Fluid-fluid levels (FFLs) are uncommon in VMs and common in lymphatic malformations (LMs). Technology has advanced since the initial description of these findings. Rates of detection of these MRI findings in VMs may have changed as MRI technology and techniques have evolved. Methods and methods A prospectively maintained database from a multidisciplinary vascular anomalies clinic was reviewed to identify patients with final diagnosis of VM or LM. Patients with reviewable contrast-enhanced MRIs were selected, reviewing the oldest MRI studies in the database against the newest MRI studies to identify equal numbers of patients from the temporal extremes. Imaging was reviewed to assess for presence of FFLs. Enhancement was quantified by measuring signal in the same location of the lesion both on pre- and postcontrast sequences Results Forty patients were identified for analysis. Twenty studies with sufficient archived imaging for review were performed between 1995 and 2006; 20 such studies were performed between 2011 and 2012. The new imaging cohort had higher rates of FFL visualization ( p = 0.001). Correlation was found between time to imaging following contrast and degree of enhancement ( p < 0.001). Inverse correlation was found between scan date and time to contrast ( p = 0.001) and scan date and enhancement ( p = 0.021). Conclusion FFLs should no longer be considered exclusionary for the diagnosis of VMs. Timing following contrast administration should be maximized to increase degree of enhancement to confirm the diagnosis of VMs.

Development of an international core outcome set for peripheral vascular malformations: the OVAMA project.

BACKGROUND: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. OBJECTIVES: To reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS. METHODS: Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re-evaluated in an online consensus meeting. RESULTS: 167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately. CONCLUSIONS: Our recommendation is that therapeutic-efficacy studies on peripheral vascular malformations should measure at least these core outcome domains.

Infantile hemangiomas with minimal or arrested growth associated with soft tissue hypertrophy: a case series of 10 patients.

BACKGROUND: Infantile hemangiomas with minimal or arrested growth (IH-MAGs) are characterized by a proliferative component of <25% of its surface area. The co-occurrence of IH-MAGs and soft tissue anomalies is rare, and case series of this association are lacking. OBJECTIVE: We present 10 cases of IH-MAGs associated with soft tissue hypertrophy and describe their clinical features. METHODS: We reviewed all infantile hemangiomas with minimal or arrested growth seen between 2009 and 2016 in the dermatology clinic department at Hospital Santa Creu i Sant Pau, Barcelona. To collect more patients, we also requested cases from the Hemangioma Investigator Group and members of the Spanish Society of Vascular Anomalies. RESULTS: Ten patients had IH-MAGs associated with soft tissue hypertrophy; seven involving the arm and three involving the leg. All displayed a segmental pattern, a doughy and puffy texture and prominent surface veins. No significant asymmetries in limbs and no other visceral anomalies were observed at follow-up (range 15 months to 7 years). One patient reported coldness in the limb with infantile hemangioma, but RMI-angiography did not disclose a vascular malformation underneath the lesion. Ulceration was observed in three patients. The proliferative component in all IH-MAGs had faded at 1-year follow-up, while soft tissue hypertrophy and prominent vessels remained unchanged. CONCLUSIONS: In this first case series of IH-MAGS associated with soft tissue hypertrophy, soft tissue hypertrophy was not progressive and remained unchanged over time, unlike the proliferative component of classic infantile hemangioma. The origin of the prominent vessels and the higher ulceration risk are unknown; however, these findings are probably related to a minor disruption of local vessels not detected in imaging tests.

Haemangioma: clinical course, complications and management.

Despite their high incidence, most infantile haemangiomas (IH) do not require treatment as they regress spontaneously and most do not leave significant sequelae. For the subset of haemangiomas that require treatment, indications for intervention can be divided into three main categories: ulceration, disfigurement and impairment of function or vital structures. In addition, certain IH have a risk of associated structural anomalies. Given the wide heterogeneity of haemangiomas, deciding which haemangiomas need intervention and when to intervene requires a detailed knowledge of natural history and clinical indicators of increased risk.

X Chromosome-Inactivation Patterns in 31 Individuals with PHACE Syndrome.

Segmental hemangiomas of the head and neck can be associated with multiple congenital anomalies in the disorder known as PHACE syndrome (OMIM 606519) (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, and eye anomalies). All reported cases of PHACE syndrome to date have been sporadic, and the genetic basis of this disorder has not yet been established. PHACE syndrome has a striking female predominance which has raised the question of X-linked inheritance. In this study, the X chromosome-inactivation (XCI) patterns of 31 females with PHACE syndrome and their mothers were analyzed using blood-derived DNA and X-chromosome locus methylation assay. This study was performed to test the hypothesis that some cases of PHACE syndrome are due to X-linked inheritance and favorable skewing in the mothers may protect against a severe phenotype, but the clinical phenotype may be unmasked in daughters with a random pattern of X-inactivation. XCI analysis was informative in 27/31 mothers. Our results identified skewed XCI in 5 of 27 (19%) informative mothers, which is not statistically significant with a p value of 0.41. None of the mothers reported significant medical problems, although a full PHACE work-up has not been performed in these individuals. Skewed XCI in the mothers of children with PHACE was identified in only a minority of cases. Based on these results, genetic heterogeneity is likely in PHACE syndrome, although it is possible a subset of cases are caused by a mutation in an X-linked gene.

Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome.

BACKGROUND: The RASopathies are a class of human genetic syndromes that are caused by germline mutations in genes which encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Cardiofaciocutaneous (CFC) syndrome is characterized by distinctive craniofacial features, congenital heart defects, and abnormalities of the skin and hair. OBJECTIVES: Systematically to characterize the spectrum of dermatological findings in mutation-positive individuals with CFC syndrome. METHODS: Dermatological surveys were designed by the authors and distributed to the study participants through CFC International or directly by the authors (K.A.R. and D.H.S.) between July 2006 and August 2009. A second follow-up survey was collected between December 2007 and August 2009. When available, digital images and medical records of the participants were obtained. Study participants included individuals with CFC syndrome who have a mutation in BRAF, MAP2K1, MAP2K2 or KRAS. RESULTS: Individuals with CFC syndrome have a variety of dermatological manifestations caused by dysregulation of the MAPK pathway in development. Numerous acquired melanocytic naevi were one of the most striking features: more than 50 naevi were reported by 23% (14/61) of participants and of those, more than 100 naevi were reported by 36% (5/14). Keratosis pilaris was reported in 80% (49/61) of cases. Ulerythema ophryogenes was common, occurring in 90% (55/61). Infantile haemangiomas occurred at a greater frequency, 26% (16/61), as compared with the general population. CONCLUSIONS: CFC syndrome has a complex dermatological phenotype with many cutaneous features, some of which allow it to be differentiated from the other Ras/MAPK pathway syndromes. Multiple café-au-lait macules and papillomas were not identified in this CFC cohort, helping to distinguish CFC from other RASopathies such as neurofibromatosis type 1 and Costello syndrome.

Cervical and intracranial arterial anomalies in 70 patients with PHACE syndrome.

BACKGROUND AND PURPOSE: Cerebral and cervical arterial abnormalities are the most common non-cutaneous anomaly in PHACE syndrome, but the location and type of arterial lesions that occur have not been systematically assessed in a large cohort. Our aim was to characterize the phenotypic spectrum of arteriopathy, assess the frequency with which different arteries are involved, and evaluate spatial relationships between arteriopathy, brain structural lesions, and hemangiomas in PHACE syndrome. MATERIALS AND METHODS: Intracranial MRA and/or CTA images from 70 children and accompanying brain MR images in 59 patients with arteriopathy and PHACE syndrome were reviewed to identify the type and location of arterial lesions and brain abnormalities. Five categories of arteriopathy were identified and used for classification: dysgenesis, narrowing, nonvisualization, primitive embryonic carotid-vertebrobasilar connections, and anomalous arterial course or origin. Univariate logistic regression analyses were performed to test for associations between arteriopathy location, hemangiomas, and brain abnormalities. RESULTS: By study design, all patients had arterial abnormalities, and 57% had >1 form of arteriopathy. Dysgenesis was the most common abnormality (56%), followed by anomalous course and/or origin (47%), narrowing (39%), and nonvisualization (20%). Primitive embryonic carotid-vertebrobasilar connections were present in 20% of children. Hemangiomas were ipsilateral to arteriopathy in all but 1 case. The frontotemporal and/or mandibular facial segments were involved in 97% of cases, but no other specific associations between arteriopathy location and hemangioma sites were detected. All cases with posterior fossa anomalies had either ICA anomalies or persistent embryonic carotid-basilar connections. CONCLUSIONS: The arteriopathy of PHACE syndrome commonly involves the ICA and its embryonic branches, ipsilateral to the cutaneous hemangioma, with dysgenesis and abnormal arterial course the most commonly noted abnormalities. Brain abnormalities are also typically ipsilateral.

Segmental pigmentation disorder.

BACKGROUND: There is little published information about segmental hypo- and hyperpigmentation pigmentation disorder (SegPD) although it is a relatively common problem in paediatric dermatology. OBJECTIVES: To define the spectrum of disease, clinical presentation and associations in cases of SegPD and to clarify further the terminology in defining patterned hypo- and hyperpigmentation in children. METHODS: This was a retrospective review of cases in an academic paediatric dermatology practice. Thirty-nine patients referred for dermatological evaluation were diagnosed with SegPD. Demographic and clinical features, and distribution and frequency of extracutaneous abnormalities were measured. RESULTS: Twenty female and 19 male patients were included in the study; 33 out of the 39 were referred specifically for a pigmentation abnormality. The mean age at onset was 3·4 months (median age 0·25 months). Family history was positive in two patients. Most (30/39; 77%) had segmental hyperpigmentation whereas nine of 39 (23%) had hypopigmentation. Patches were more often delineated at the ventral midline (32/39) than on the dorsal midline (7/39). The distribution of lesions was as follows: areas of the torso were most often affected (77%) and when the face, neck, arms and legs were affected pigmentation usually extended onto the torso; six patients had SegPD localized to the face. Only three of the 39 patients had extracutaneous abnormalities - atrial septal defect, strabismus with retinal hypopigmentation and a bronchogenic cyst - but the relationship to SegPD was uncertain and none had neurological abnormalities. CONCLUSIONS: SegPD is a relatively common pigmentary anomaly and most affected individuals are otherwise healthy. We propose reviving the term 'segmental pigmentation disorder' coined by Metzker and colleagues to describe children with segmental and block-like hypo-/hyperpigmentation with midline demarcation.

Infantile hemangiomas: a look back and future directions.

Over the past 10 years, there have been significant advancements in our understanding of the biology and natural history of infantile hemangiomas (IH). Research into their pathogenesis has led to many new discoveries including the first mouse model recapitulating hemangioma growth and genes such as the vascular Endothelial Growth Factor Receptor (VEGFR) which may be intimately involved in their proliferation. Large prospective studies have born out important data on the natural history, complications and structural associations of these fascinating vascular tumors. In addition, new therapies have emerged which appear to be very effective. In the following article, a summary of major contributions over the past decade is outlined.

A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications.

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "segmental" hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

Corticosteroid treatment of periorbital haemangioma of infancy: a review of the evidence.

AIM: To systematically review the literature for corticosteroid treatment of periorbital haemangioma of infancy (HOI) and determine the relative efficacy and safety of oral, topical and intralesional corticosteroids. METHODS: PubMed and the Cochrane Library were queried using keywords, and further articles were obtained by reviewing bibliographies. Inclusion and exclusion criteria were applied to create a subset of literature for analysis. RESULTS: Systematic review revealed 81 original reports of periorbital HOI cases treated with steroids. Most studies and case series failed to document refractive error or visual acuity before and after treatment. Of cases meeting inclusion criteria, five patients received topical steroids and 25 patients received intralesional steroids. Patients receiving intralesional injections tended to demonstrate reduced astigmatism at follow up after treatment (21 of 28). The lack of studies with relevant objective ophthalmological end points prevented statistical meta-analysis. CONCLUSION: Intralesional injections may reduce refractive error, while the efficacy of topical steroids is unclear. Studies measuring objective ophthalmic data before and after treatment are sparse, and more studies are needed to determine the relative efficacy of different steroids. There are insufficient data to estimate the incidence of steroid side effects in patients treated with steroids for periorbital HOI or complications of intralesional injections in particular.

Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma.

BACKGROUND: Infantile hemangiomas are common tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution-and for their expression of a unique immunophenotype shared by placental microvessels. Occasional "hemangiomas" differ from the classic form in presenting fully formed at birth, then following a static or rapidly involuting course. These congenitally fully developed lesions have generally been assumed to be clinical variants of more typical, postnatally developing hemangiomas. This assumption has not been tested by rigorous histologic and immunophenotypic comparisons. OBJECTIVE: To compare the histologic and immunohistochemical features of congenital nonprogressive hemangiomas with those of typical, postnatally proliferating, hemangiomas. DESIGN: All cellular vascular tumors resected from infants younger than 4 months at Arkansas Children's Hospital, Little Rock, over the past 20 years (43 lesions from 36 patients) were first characterized histologically and immunohistochemically, then clinically by chart review. SETTING: A university-affiliated pediatric hospital. MAIN OUTCOME MEASURES: Histologic appearance, immunoreactivity for the infantile hemangioma-associated antigens GLUT1 and LeY, and clinical behavior. RESULTS: Congenital nonprogressive hemangiomas differed from postnatally proliferating infantile hemangiomas in histologic appearance and immunohistochemical profile. Distinguishing pathologic features of these tumors were lobules of capillaries set within densely fibrotic stroma containing hemosiderin deposits; focal lobular thrombosis and sclerosis; frequent association with multiple thin-walled vessels; absence of "intermingling" of the neovasculature with normal tissue elements; and lack of immunoreactivity for GLUT1 and LeY. CONCLUSION: Congenital nonprogressive hemangiomas are histologically and immunophenotypically distinct from classically presenting hemangiomas of infancy, unlikely to be related to the latter in pathogenesis.

Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study.

SCID is a heterogeneous group of disorders characterized by defective T cell and B cell function. Eczematous and morbilliform eruptions are common, and graft-versus-host disease (GVHD) due to maternal engraftment has been documented. We sought to better characterize SCID-related cutaneous disease observed prior to BMT and to compare the eruption to conventional GVHD. Medical records of 51 patients with SCID treated between 1982 and 1999 were reviewed. Ten of 51 (20%) had rash and evidence of maternal engraftment prior to BMT (study group). Eleven of 51 (22%) had no rash or evidence of engraftment pre-BMT but developed GVHD following transplant (control group). Skin biopsies were available for review for 8/10 of the study group and for 8/11 of the control group. Cutaneous findings consisted of a scaling, erythematous maculopapular eruption spread widely over the trunk and extremities, with near-erythroderma in some patients. Microscopically, biopsies from the study group differed significantly from controls. Key differences included parakeratosis (P < or = 0.01), psoriasiform hyperplasia (P < or = 0.04) and spongiosis (P < or = 0.04). The dermatopathologic findings of transplacental GVHD differ from the pattern of post-transplant GVHD. A 'psoriasiform-lichenoid-spongiotic' pattern with necrotic keratinocytes should trigger consideration of SCID and maternal engraftment in the dermatopathologic evaluation of eruptions of infancy.

Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation.

OBJECTIVES: To determine the efficacy of systemic corticosteroid therapy in treating enlarging, problematic cutaneous hemangiomas and to assess the relationship of dose to response and adverse effects. DESIGN: A quantitative systematic literature review was performed and inclusion and exclusion criteria were applied. SETTING: Patients were treated in primary care, referral centers, and institutional practices. Most patients were ambulatory, although some required hospitalization. PATIENTS: Inclusion criteria were original case series with a minimum of 5 patients with enlarging, problematic cutaneous hemangiomas treated with systemic corticosteroids. Exclusion criteria were being older than 2 years, receiving simultaneous other treatments, being lost to follow-up, or having insufficient information. Twenty-four original case series met inclusion criteria; 10 case series remained (184 patients) after exclusion criteria were applied. INTERVENTION: Patients were given a mean prednisone equivalent daily dose of 2.9 mg/kg (95% confidence interval [CI], 2.7-3.1 mg/kg) for a mean of 1.8 months (95% CI, 1.5-2.2 months). MAIN OUTCOME MEASURES: Response and rebound rates and dose-response and adverse effects-response relationships in responders vs nonresponders. RESULTS: Response was 84% (95% CI, 78%-89%; range, 60%-100%) and rebound was 36% (95% CI, 29%-44%; range, 0%-65%). A significant difference was found between the mean dose administered to responders vs nonresponders (P<.001). No significant difference was observed as to the occurrence of adverse effects (P =.3). CONCLUSION: Systemic corticosteroid treatment seems to be effective for problematic cutaneous hemangiomas of infancy.

Do hair care practices affect the acquisition of tinea capitis? A case-control study.

OBJECTIVE: To determine the influences of hair-grooming practices and environmental factors as risk factors for the acquisition of tinea capitis (TC) in children. DESIGN: Case-control study comparing children with culture-proved TC with age-, sex-, and race-matched control subjects without scalp disease. SETTING: A multicenter study involving 3 urban referral centers in the United States. PARTICIPANTS: A convenience sample of 66 patients aged 12 years and younger presenting to pediatric dermatology clinics with clinical evidence of TC were enrolled as cases. Matched control subjects (n = 68), without known scalp disease, were enrolled from the outpatient pediatric clinics at the same institutions. RESULTS: Significant associations with TC in the conditional logistic regression model were a prior history of TC (odds ratio, 3.11; 95% confidence interval, 1.02-9.43; P =.04) and exposure to TC (odds ratio, 16.32; 95% confidence interval, 3.55-75.16; P =.001). The use of a hair conditioner was statistically significant in the univariable model but not in the multivariable model (odds ratio, 0.46; 95% confidence interval, 0.20-1.08; P =.07). Hairstyling, frequency of washing, use of oils or grease, and other hair care practices were not shown to be associated with the presence of TC. CONCLUSIONS: Hair-grooming practices do not appear to play a major role in the acquisition of TC. Hair conditioners may be protective in children at risk for TC, but further studies are needed to confirm this finding.

The many faces of PHACE syndrome.

OBJECTIVES: PHACE is an acronym coined to describe a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, large facial hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation, and eye abnormalities. We evaluated the spectrum of disease and significance of potential underlying brain anomalies among affected children. STUDY DESIGN: The records of 14 patients with PHACE syndrome, evaluated between 1995 and 2000, were retrospectively reviewed. A literature review revealed 116 additional cases. RESULTS: PHACE syndrome represents a spectrum of anomalies, because most affected children have only one extracutaneous manifestation. The syndrome is associated with a high incidence of arterial and structural central nervous system anomalies with secondary neurologic sequelae. The potential for progressive neurovascular disease also exists among those patients with anomalous vasculature. CONCLUSION: PHACE syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac, and neurologic assessment.