Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Acute Genital Ulceration After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination and Infection.

Reactive, nonsexually related acute genital ulceration, also known as Lipschütz ulcer, is a nonsexually related ulceration involving the vulva, most commonly affecting girls and adolescent women in response to infection. Herein, we describe 3 female patients with acute genital ulceration occurring after severe acute respiratory syndrome coronavirus 2 vaccination or natural infection.

Ocular Complications in PHACE Syndrome: A True Association or a Coincidence?

OBJECTIVE: To characterize the risk for ocular complications in patients with PHACE syndrome. STUDY DESIGN: This study included consecutive patients with PHACE syndrome who were seen at Lurie Children's Hospital of Chicago from January 2000 through May 2017. A complete ophthalmic examination was performed in all patients, with extra attention for findings typically associated with PHACE syndrome. RESULTS: Thirty patients (67% female, median age of onset 0.08 months) were included: 38 (93%) demonstrated a segmental infantile hemangioma distribution. Twenty-one (70%) cases had a periocular involvement, and 47% had an infantile hemangioma with a deep component. Among 21 patients with periocular distribution, 9 had ocular complications secondary to the periocular location (mainly ptosis, nasolacrimal duct obstruction, and refractive errors), and one had an ocular complication specifically associated with PHACE syndrome (Horner syndrome). None of the patients without periocular distribution had an ocular complication. CONCLUSIONS: In patients with PHACE syndrome who have a periocular infantile hemangioma, a complete eye examination is recommended. Although specific ocular anomalies related to PHACE syndrome are rare, serious ocular complications secondary to the location of the hemangioma may be present. Eye examination in patients with PHACE syndrome without a periocular infantile hemangioma distribution is likely of low yield.

Infantile Hemangiomas in Twins: A Prospective Cohort Study.

BACKGROUND: Twins have a higher-than-expected risk of infantile hemangiomas (IHs), but the exact reasons for this association are not clear. Comparing concordant and discordant twin pairs might help elucidate these factors and yield more information about IH risk factors. METHODS: A prospective cohort study of twin pairs from 12 pediatric dermatology centers in the United States, Canada, Argentina, and Spain was conducted. Information regarding maternal pregnancy history, family history of vascular birthmarks, zygosity (if known), and pregnancy-related information was collected. Information regarding twins (N = 202 sets) included birthweight, gestational age (GA), presence or absence of IHs, numbers and subtypes of IHs, presence of other birthmarks, and other medical morbidities. RESULTS: Two hundred two sets of twins were enrolled. Concordance for IH was present in 37% of twin pairs. Concordance for IH was inversely related to gestational age (GA), present in 42% of GA of 32 weeks or less, 36% of GA of 33 to 36 weeks, and 32% of GA of 37 weeks or more. Twins of GA of 34 weeks or less were more than two and a half times as likely to be concordant as those of GA of 35 weeks or more (odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.42-4.99; p < 0.01). In discordant twins, lower birthweight conferred a high risk of IH; of the 64 sets of twins with 10% or greater difference in weight, the smaller twin had IH in 62.5% (n = 40) of cases, versus 37.5% (n = 24) of cases in which the higher-birthweight twin was affected. Zygosity was reported in 188 twin sets (93%). Of these, 78% were dizygotic and 22% monozygotic. There was no statistically significant difference in rates of concordance between monozygotic twins (43%, 18/42) and dizygotic twins (36%, 52/146) (p = 0.50). In multivariate analysis comparing monozygotic and dizygotic twins, adjusting for effects of birthweight and sex, the likelihood of concordance for monozygotic was not appreciably higher than that for dizygotic twins (OR = 1.14, 95% CI = 0.52-2.49). Female sex also influenced concordance, confirming the effects of female sex on IH risk. The female-to-male ratio was 1.7:1 in the entire cohort and 1.9:1 in those with IH. Of the 61 concordant twin sets with known sex of both twins, 41% were female/female, 43% were female/male, and 16% were male/male. CONCLUSIONS: These findings suggest that the origin of IHs is multifactorial and that predisposing factors such as birthweight, sex, and GA may interact with one another such that a threshold is reached for clinical expression.

Gastrointestinal bleeding in infantile hemangioma: a complication of segmental, rather than multifocal, infantile hemangiomas.

OBJECTIVE: To highlight an association of facial segmental hemangiomas with gastrointestinal bleeding in infants with infantile hemangiomas. STUDY DESIGN: We conducted a multicenter retrospective case series study. RESULTS: Ten female patients met study inclusion criteria; 8 were Caucasian, 9 had a facial segmental hemangioma, and 9 cases met the diagnostic criteria for definitive posterior fossa malformations, hemangioma, arterial lesions, cardiac anomalies/coarctation of the aorta and eye abnormalities syndrome with abnormalities of the aorta and cerebral arteriopathy. Severe gastrointestinal bleeding requiring blood transfusion occurred in 9 cases, with age at presentation of gastrointestinal bleeding ranging from 8 days to 6 months. When detected, the location of the hemangioma in the small intestine was in the distribution of the superior mesenteric artery. More than one agent was required to control the gastrointestinal bleeding, including oral or intravenous steroids, vincristine, oral propranolol, interferon, and resection of the small intestine. All cases needed ongoing support care with red blood cell transfusions. CONCLUSIONS: Gastrointestinal bleeding is a rare complication of true infantile hemangioma. The segmental pattern of the cutaneous hemangioma associated with gastrointestinal bleeding should suggest a segmental infantile hemangioma of the lower gastrointestinal tract.

Prospective study of spinal anomalies in children with infantile hemangiomas of the lumbosacral skin.

OBJECTIVE: To prospectively evaluate a cohort of patients with infantile hemangioma in the midline lumbosacral region for spinal anomalies to determine the positive predictive value of infantile hemangioma for occult spinal anomalies and to make evidence-based recommendations for screening. STUDY DESIGN: A multicenter prospective cohort study was performed at 9 Hemangioma Investigator Group sites. RESULTS: Intraspinal abnormalities were detected in 21 of 41 study participants with a lumbosacral infantile hemangioma who underwent a magnetic resonance imaging evaluation. The relative risk for all patients with lumbosacral infantile hemangiomas for spinal anomalies was 640 (95% confidence interval [CI], 404-954), and the positive predictive value of infantile hemangioma for spinal dysraphism was 51.2%. Ulceration of the hemangioma was associated with a higher risk of having spinal anomalies. The presence of additional cutaneous anomalies also was associated with a higher likelihood of finding spinal anomalies; however, 35% of the infants with isolated lumbosacral infantile hemangiomas had spinal anomalies, with a relative risk of 438 (95% CI, 188-846). The sensitivity for ultrasound scanning to detect spinal anomalies in this high-risk group was poor at 50% (95% CI, 18.7%-81.3%), with a specificity rate of 77.8% (95% CI, 40%-97.2%). CONCLUSIONS: Infants and children with midline lumbosacral infantile hemangiomas are at increased risk for spinal anomalies. Screening magnetic resonance imaging is recommended for children with these lesions.

LUMBAR: association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies.

OBJECTIVE: To define the clinical spectrum of regional congenital anomalies associated with large cutaneous hemangiomas of the lower half of the body, clarify risk for underlying anomalies on the basis of hemangioma location, and provide imaging guidelines for evaluation. STUDY DESIGN: We conducted a multi-institutional, retrospective case analysis of 24 new patients and review of 29 published cases. RESULTS: Hemangiomas in our series tended to be "segmental" and often "minimal growth" in morphology. Such lesions were often extensive, covering the entire leg. Extensive limb hemangiomas also showed potential for extracutaneous anomalies, including underlying arterial anomalies, limb underdevelopment, and ulceration. The cutaneous hemangioma and underlying anomalies demonstrated regional correlation. Myelopathies were the most common category of associated anomalies. CONCLUSIONS: We propose the acronym "LUMBAR" to describe the association of Lower body hemangioma and other cutaneous defects, Urogenital anomalies, Ulceration, Myelopathy, Bony deformities, Anorectal malformations, Arterial anomalies, and Renal anomalies. There are many similarities between LUMBAR and PHACE syndrome, which might be considered regional variations of the same. Although guidelines for imaging are suggested, prospective studies will lead to precise imaging recommendations and help determine true incidence, risk and long-term outcomes.

Multicenter prospective study of ulcerated hemangiomas.

OBJECTIVE: To identify clinical features of infants with ulcerated infantile hemangiomas. STUDY DESIGN: Cross-sectional analysis was conducted within a prospective cohort study of children with infantile hemangiomas. Children younger than 12 years of age were recruited. Demographic and prenatal/perinatal information was collected. Hemangioma size, location, subtype, course, complications, and treatments were recorded. RESULTS: One thousand ninety-six patients were enrolled, and 173 (15.8%) patients experienced ulceration. Ulceration occurred in 192 (9.8%) of 1960 [corrected] total hemangiomas. Hemangiomas with ulcerations were more likely large, mixed clinical type, segmental morphologic type, and located on the lower lip, neck, or anogenital region. Ulceration occurred at a median age of 4 months, most often during the proliferative phase. Children with ulcerated hemangiomas were more likely to present to a pediatric dermatologist at a younger age and to require treatment. Bleeding occurred in 41% of ulcerated lesions but was rarely of clinical significance. Infection occurred in 16%. CONCLUSIONS: Ulceration occurs in nearly 16% of patients with infantile hemangiomas, most often by 4 months of age, during the proliferative phase. Location, size, and clinical and morphologic type are associated with an increased risk for development of ulceration.

Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics.

OBJECTIVES: To characterize demographic, prenatal, and perinatal features of patients with infantile hemangiomas and to determine the importance of these factors in predicting rates of complication and treatment. STUDY DESIGN: We conducted a prospective study at 7 U.S. pediatric dermatology clinics. A consecutive sample of 1058 children, aged 12 years and younger, with infantile hemangiomas was enrolled between September 2002 and October 2003. A standardized questionnaire was used to collect demographic, prenatal, perinatal, and hemangioma-specific data. National Vital Statistic System Data (NVSS) was used to compare demographic variables and relevant rates of prenatal events. RESULTS: In comparison with the 2002 United States National Vital Statistics System birth data, we found that infants with hemangiomas were more likely to be female, white non-Hispanic, premature (P < .0001) and the product of a multiple gestation (10.6% versus 3.1%; P < .001). Maternal age was significantly higher (P < .0001), and placenta previa (3.1%) and pre-eclampsia (11.8%) were more common. CONCLUSIONS: Infants with hemangiomas are more likely to be female, white non-Hispanic, premature, and products of multiple gestations. Prenatal associations include older maternal age, placenta previa, and pre-eclampsia. No demographic, prenatal, and perinatal factors predicted higher rates of complications or need for treatment.

Cutaneous manifestations of hyper-IgE syndrome in infants and children.

We describe 8 children with hyper-IgE syndrome who had papulopustular eruption on the face and scalp in the first year of life. Seven of the 8 patients had persistent peripheral eosinophilia and 3 had leukocytosis noted before diagnosis. Skin biopsy specimens in 6 patients revealed spongiosis and perivascular dermatitis and/or folliculitis with a predominance of eosinophils. Two patients had bone fractures and osteopenia. Recurrent pneumonia occurred in 6 children and pneumatoceles in 5. The diagnosis of hyper-IgE syndrome was made an average of 18 months after the onset of the initial papulopustular eruption. These findings may lead to earlier recognition of the disease and institution of appropriate treatment.