Kimberly A. Horii

Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment

OBJECTIVES. Infantile hemangiomas are the most common tumor of infancy. Risk factors for complications and need for treatment have not been studied previously in a large prospective study. This study aims to identify clinical characteristics associated with complications and the need for therapeutic intervention. PATIENTS AND METHODS. We conducted a prospective cohort study at 7 US pediatric dermatology clinics with a consecutive sample of 1058 children, aged ≤12 years, with infantile hemangiomas enrolled between September 2002 and October 2003. A standardized questionnaire was used to collect data on each patient and each hemangioma, including clinical characteristics, complications, and treatment. RESULTS. Twenty-four percent of patients experienced complications related to their hemangioma(s), and 38% of our patients received some form of treatment during the study period. Hemangiomas that had complications and required treatment were larger and more likely to be located on the face. Segmental hemangiomas were 11 times more likely to experience complications and 8 times more likely to receive treatment than localized hemangiomas, even when controlled for size. CONCLUSIONS. Large size, facial location, and/or segmental morphology are the most important predictors of poor short-term outcomes as measured by complication and treatment rates.

Growth characteristics of infantile hemangiomas: implications for management.

OBJECTIVES. Infantile hemangiomas often are inapparent at birth and have a period of rapid growth during early infancy followed by gradual involution. More precise information on growth could help predict short-term outcomes and make decisions about when referral or intervention, if needed, should be initiated. The objective of this study was to describe growth characteristics of infantile hemangioma and compare growth with infantile hemangioma referral patterns. METHODS. A prospective cohort study involving 7 tertiary care pediatric dermatology practices was conducted. Growth data were available for a subset of 526 infantile hemangiomas in 433 patients from a cohort study of 1096 children. Inclusion criteria were age younger than 18 months at time of enrollment and presence of at least 1 infantile hemangioma. Growth stage and rate were compared with clinical characteristics and timing of referrals. RESULTS. Eighty percent of hemangioma size was reached during the early proliferative stage at a mean age of 3 months. Differences in growth between hemangioma subtypes included that deep hemangiomas tend to grow later and longer than superficial hemangiomas and that segmental hemangiomas tended to exhibit more continued growth after 3 months of age. The mean age of first visit was 5 months. Factors that predicted need for follow-up included ongoing proliferation, larger size, deep component, and segmental and indeterminate morphologic subtypes. CONCLUSIONS. Most infantile hemangioma growth occurs before 5 months, yet 5 months was also the mean age at first visit to a specialist. Recognition of growth characteristics and factors that predict the need for follow-up could help aid in clinical decision-making. The first few weeks to months of life are a critical time in hemangioma growth. Infants with hemangiomas need close observation during this period, and those who need specialty care should be referred and seen as early as possible within this critical growth period.

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.

Atopic Dermatitis in Children in the United States, 1997–2004: Visit Trends, Patient and Provider Characteristics, and Prescribing Patterns

OBJECTIVE. Atopic dermatitis is the most common chronic inflammatory skin disease of childhood and is increasing in prevalence throughout the world. Morbidity and resource use for atopic dermatitis are comparable to other chronic diseases. Topical corticosteroids are first-line therapeutic agents for atopic dermatitis; topical calcineurin inhibitors are considered second-line agents for patients who are older than 2 years. The aims of this study were to examine trends in visits for atopic dermatitis in children in the United States between 1997 and 2004, identify factors that were associated with a pediatric visit for atopic dermatitis, and assess changes in the treatment of atopic dermatitis over time. METHODS. Visits for atopic dermatitis by children (0–18 years) to office-based physicians and hospital outpatient departments using 1997–2004 National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey databases were analyzed. Medication prescribing rates during 2 time periods (1997–2000 and 2001–2004) were also analyzed. RESULTS. There were an estimated 7.4 million visits for atopic dermatitis. Statistically significant differences in patients with atopic dermatitis included age 2 to 5 years, black race, Asian race, and specialist or hospital outpatient clinic evaluation. The increase in atopic dermatitis visits per year was statistically significant. No statistical differences in prescribing rates were identified between the 2 time periods. Between 1997 and 2000, topical corticosteroids were prescribed in 34% of visits, decreasing to 25% between 2001 and 2004. Between 2001 and 2004, topical calcineurin inhibitors were prescribed in 23% of visits. In the same period, topical corticosteroids were prescribed in 24% of visits by children who were younger than 2 years; topical calcineurin inhibitors were prescribed in 22% of visits. CONCLUSIONS. Visits for atopic dermatitis in children are increasing. A recommended first-line treatment was prescribed in a minority of the visits.

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.

Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

Abstract:  Multiple cutaneous infantile hemangiomas have been associated with hepatic hemangiomas. Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. The aim of this study was to determine the frequency with which hepatic hemangiomas occur in infants with five or more cutaneous infantile hemangiomas compared to those with one to four cutaneous infantile hemangiomas and to characterize the clinical features of these hepatic hemangiomas. A multicenter prospective study of children with cutaneous infantile hemangiomas was conducted at pediatric dermatology clinics at Hemangioma Investigator Groups sites in the United States, Canada, and Spain between October 2005 and December 2008. Data were collected, and abdominal ultrasonography was performed on infants younger than 6 months old with five or more cutaneous infantile hemangiomas and those with one to four cutaneous infantile hemangiomas. Twenty‐four (16%) of the 151 infants with five or more cutaneous infantile hemangiomas had hepatic hemangiomas identified on abdominal ultrasound, versus none of the infants with fewer than five (p = 0.003). Two of the 24 infants with hepatic hemangiomas received treatment specifically for their hepatic hemangiomas. Infants with five or more cutaneous infantile hemangiomas have a statistically significantly greater frequency of hepatic hemangiomas than those with fewer than 5. These findings support the recommendation of five or more cutaneous infantile hemangiomas as a threshold for screening infants younger than 6 months old for hepatic hemangiomas but also demonstrate that the large majority of these infants with hepatic hemangiomas do not require treatment.

Comparison of infantile hemangiomas in preterm and term infants: a prospective study.

1. Boyd AS, Neldner KH. The isomorphic response of Koebner. Int J Dermatol. 1990;29(6):401-410. 2. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graftversus-host disease, I: diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-956. 3. Rubin AI, Stiller MJ. A listing of skin conditions exhibiting the Koebner and pseudo-Koebner phenomena with eliciting stimuli. J Cutan Med Surg. 2002; 6(1):29-34. 4. Ochs LA, Blazar BR, Roy J, Rest EB, Weisdorf DJ. Cytokine expression in human cutaneous chronic graft-versus-host disease. Bone Marrow Transplant. 1996;17(6):1085-1092. 5. Svegliati S, Olivieri A, Campelli N, et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood. 2007;110(1):237-241.

Measuring the Severity of Infantile Hemangiomas: Instrument Development and Reliability

OBJECTIVES To develop instruments that measure the severity of infantile hemangiomas (Hemangioma Severity Scale [HSS]) and the complications of infantile hemangiomas for longitudinal use (Hemangioma Dynamic Complication Scale [HDCS]). DESIGN Instrument development and reliability study. SETTING Academic research. PARTICIPANTS The HSS and the HDCS were developed through the collaborative effort of members of the Hemangioma Investigator Group Research Core, an expert multi-institutional research group. After development of the scales, 13 pediatric dermatologists used the HSS to score 20 different hemangiomas. In addition, 12 pediatric dermatologists used the HDCS to score hemangioma-related complications for 24 clinical scenarios. Interrater and intrarater reliability was measured for both scales. MAIN OUTCOME MEASURES Interrater and intrarater reliability. RESULTS For the HSS, interrater reliability and intrarater reliability exceeded 99%. Similarly, the HDCS had a high rate of interrater agreement; for individual items, agreement among raters was 67% to 100%, with most clinical scenarios demonstrating greater than 90% agreement. Intrarater reliability was excellent for all individual items of the HDCS. CONCLUSION The HSS and the HDCS are reliable scales that can be used to measure the severity of infantile hemangiomas, including the severity of complications for longitudinal use.

Risk of Hepatic Hemangiomas in Infants With Large Hemangiomas

decisions. Because severity scorings differed mainly in diverse estimations of the involved area and induration of the lesions, one may speculate that the divergence might have resulted from the inability of the teledermatologists to see the entire body and to palpate the lesions, or it might have resulted from some flaws of the PASI scoring system for which an interrater variability of up to 8.1 PASI scores has been described. In our study, the interrater variability was very low (Table), indicating that mobile teledermatology is a feasible method for monitoring disease severity in patients with psoriasis. Larger controlled studies are required to evaluate the impact of remote follow-up care on patient empowerment and its influence on the therapeutic outcome.

Topical Timolol Maleate Treatment of Infantile Hemangiomas

BACKGROUND: There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a β-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol’s effectiveness, discern characteristics associated with response, and document reported adverse events. METHODS: A multicenter retrospective cohort study of 731 patients treated with topical timolol was completed at 9 centers. Inclusion required an IH suitable for timolol in the treating physician’s judgment and access to clinical details including photographs. Logistic regression analysis and descriptive statistics were performed. Primary outcome measures were efficacy assessed by using visual analog scales for color and for size, extent, and volume from review of digital photographs taken as standard of care. RESULTS: Most IHs were localized (80.1%) and superficial (55.3%). Risk of disfigurement was the most common indication for therapy (74.3%). Duration of therapy (P < .0001), initial thinness (P = .008), and subtype (P = .031) were significant predictors of response. Best response occurred in superficial IHs <1 mm thick. Fifty-three (7.3%) required subsequent therapy with systemic β-blocker. Adverse events were mild, occurring in 25 (3.4%) patients. No cardiovascular side effects were documented. CONCLUSIONS: Timolol seems to be a well-tolerated, safe treatment option with moderate to good effectiveness, demonstrating best response in thin, superficial IHs regardless of pretreatment size. Timolol can be recommended as an alternative to systemic β-blockers and watchful waiting for many patients.