J. Mazereeuw-Hautier

Propranolol for Severe Infantile Hemangiomas: Follow-Up Report

OBJECTIVE: Infantile hemangiomas (IHs) are the most-common soft-tissue tumors of infancy. We report the use of propranolol to control the growth phase of IHs. METHODS: Propranolol was given to 32 children (21 girls; mean age at onset of treatment: 4.2 months) after clinical and ultrasound evaluations. After electrocardiographic and echocardiographic evaluations, propranolol was administered with a starting dose of 2 to 3 mg/kg per day, given in 2 or 3 divided doses. Blood pressure and heart rate were monitored during the first 6 hours of treatment. In the absence of side effects, treatment was continued at home and the child was reevaluated after 10 days of treatment and then every month. Ultrasound measurements were performed after 60 days of treatment. RESULTS: Immediate effects on color and growth were noted in all cases and were especially dramatic in cases of dyspnea, hemodynamic compromise, or palpebral occlusion. In ulcerated IHs, complete healing occurred in <2 months. Objective clinical and ultrasound evidence of longer-term regression was seen in 2 months. Systemic corticosteroid treatment could be stopped within a few weeks. Treatment was administered for a mean total duration of 6.1 months. Relapses were mild and responded to retreatment. Side effects were limited and mild. One patient discontinued treatment because of wheezing. CONCLUSION: Propranolol administered orally at 2 to 3 mg/kg per day has a consistent, rapid, therapeutic effect, leading to considerable shortening of the natural course of IHs, with good clinical tolerance.

A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma

BACKGROUND Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

Topical corticosteroid phobia in atopic dermatitis: a study of its nature, origins and frequency

Background  Topical corticosteroids remain the mainstay of atopic dermatitis therapy. Many atopic dermatitis therapeutic failures appear to be attributable to poor adherence to treatment due to topical corticosteroid phobia.

Efficacy of Propranolol in Hepatic Infantile Hemangiomas with Diffuse Neonatal Hemangiomatosis

We report the rapid and dramatic efficacy of propranolol in 8 infants with infantile hepatic hemangiomas. The degree of response varied from a significant improvement to a complete resolution of hepatic lesions. Heart failure and hypothyroidism resolved, and hepatomegaly decreased. No side-effects of the drug were noted.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation

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.

Update on the epidermal differentiation complex.

On human chromosome 1q21, a 2-Mb region called the epidermal differentiation complex comprises many genes encoding structural and regulatory proteins that are of crucial importance for keratinocyte differentiation and stratum corneum properties. Apart from those for involucrin and loricrin, most of the genes are organized in four families: the genes encoding EF-hand calcium-binding proteins of the S100A family, the genes encoding the small proline rich proteins (SPRRs) and the late cornified envelope (LCE) proteins, two families of cornified cell envelope components, and the genes encoding the S100-fused type proteins (SFTPs). This review focuses on the SPRRs, LCE proteins and SFTPs. It describes their structures, their specific functions and, when known, the mechanisms involved in the regulation of their expression. It also highlights their possible involvement in skin diseases.

Prevalence and Risk Factors for Xerosis in the Elderly: A Cross-Sectional Epidemiological Study in Primary Care

Background: Limited information is available concerning the prevalence and risk factors of xerosis in the elderly. Objective: To establish the prevalence of xerosis and associated factors in elderly patients. Methods: A national, multicenter, observational, cross-sectional study in patients aged 65 or older was performed. The data collected by general practitioners were demographics and medical history, including history of atopic disease. Xerosis was evaluated using the Overall Dry Skin score. Results: 756 patients were included. The prevalence of xerosis was 55.6%. Xerosis was significantly associated with older age (OR: 1.48, 95% CI: 1.16–1.89), female sex (OR: 1.80, 95 CI%: 1.29–2.53), treatments that can potentially cause xerosis (OR: 2.21, 95 CI%: 1.54–3.17), itching during sweating (OR: 7.11, 95% CI: 3.90–12.95), a history of dry skin (OR: 2.89, 95% CI: 1.65–5.08) and a history of atopic dermatitis (OR: 3.60, 95% CI: 1.99–6.52). Conclusion: Xerosis is highly prevalent in the elderly. A history of atopy, especially atopic dermatitis, is associated with an increased risk of xerosis in the elderly.

Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: A systematic review and meta-analysis

BACKGROUND There is controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis (AD). OBJECTIVE To assess the risk of lymphoma and the role of topical treatments in patients with AD. METHODS A systematic literature search and a separate meta-analysis were performed on case control and cohort studies. RESULTS Of the 3979 articles retrieved, 24 references met the inclusion criteria. In cohort studies, the risk of lymphoma was slightly increased, with a relative risk (RR) of 1.43 (95% confidence interval [CI], 1.12-1.81). In case control studies, no significant increased risk of lymphoma was found, with an odds ratio (OR) of 1.18 (95% CI, 0.94-1.47). Severity of AD was a significant risk factor. Highly potent topical steroids were associated with an increased risk of lymphoma. For topical calcineurin inhibitors (TCIs), a significant association between tacrolimus and mostly skin lymphoma was found in 1 study. LIMITATIONS Confusion between severe AD and cutaneous T-cell lymphoma may account for part of the increased risk of lymphoma in patients with AD. CONCLUSION This systematic literature review shows a slightly increased risk of lymphoma in patients with AD. Severity of AD appears to be a significant risk factor. The role of topical steroids and TCIs is unlikely to be significant.

Segmental and nonsegmental childhood vitiligo has distinct clinical characteristics: A prospective observational study

BACKGROUND Vitiligo often starts in childhood. It is traditionally divided into segmental vitiligo and nonsegmental vitiligo. There are limited data regarding the clinical characteristics of both forms and no comparative study has been performed. OBJECTIVE To compare the clinical features of nonsegmental and segmental vitiligo in children. PATIENTS AND METHODS We performed a prospective observational study. Consecutive children with vitiligo seen between October 2005 and December 2007 in the 11 French Departments of Pediatric Dermatology were included. A standardized evaluation was completed after total body clinical examination. A second examination was performed 1 year after inclusion. The clinical characteristics of segmental vitiligo and nonsegmental vitiligo were compared. RESULTS A total of 114 children with vitiligo were included. Compared with segmental vitiligo, nonsegmental vitiligo was associated with a higher number of lesions (more than 5 patches in 65.17% vs 20% of patients, P < .0001) and a larger body surface area of involvement (9.8% +/- 2.51% vs 3.48% +/- 1.6%, P +/- .01). A higher incidence of the Koebner phenomenon (47.19% vs 24%, P = .03), and more frequent progression of the disease (23.29% vs 5.56%, P = .043) were found in nonsegmental vitiligo. Hyperpigmented rims surrounding patches of vitiligo were only seen in nonsegmental vitiligo (8.99% vs 0% (P = .007). Sixty-four children (56%) had laboratory investigations performed; thyroid abnormalities were found only in nonsegmental vitiligo (11.23% vs 0%, P = .0001). LIMITATIONS Not all patients underwent laboratory investigations. CONCLUSIONS Segmental and nonsegmental types of vitiligo have distinguishing clinical characteristics.

Prevalence of inherited ichthyosis in France: a study using capture-recapture method

BackgroundInherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.MethodsCapture – recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period.ResultsThe prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 – 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 – 2.6]).ConclusionsOur results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies.