Alex Zvulunov

Autosomal Recessive Ichthyosis with Hypotrichosis Caused by a Mutation in ST14, Encoding Type II Transmembrane Serine Protease Matriptase

In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation.

Oral Propranolol Therapy for Infantile Hemangiomas Beyond the Proliferation Phase: A Multicenter Retrospective Study

Abstract:u2002 Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions’ growth or those older than 12u2003months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t‐test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120u2003months (mean 28u2003mos, median 22u2003mos). The duration of propranolol therapy ranged 1 to 8u2003months (mean 3.6u2003mos). The mean visual analog scale score before the treatment was 6.8u2003±u20032.15, and mean reduction in the visual analog scale score at the assessment was 2.6u2003±u20031.74 (pu2003<u20030.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (pu2003<u20030.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post‐proliferative phase, and should be considered as the first‐line therapy in that setting.

Efficacy and Safety of Propranolol for the Treatment of Infantile Hemangioma: A Presentation of Ninety-Nine Cases

Background: Propranolol is highly effective in the treatment of infantile hemangioma (IH), but important clinical and pharmacological data are lacking. Objective: The aims of the present study were to evaluate the efficacy of propranolol for the treatment of IH, to identify favorable prognostic factors in propranolol-treated IH, and to evaluate the safety of propranolol for the treatment of IH. Methods: Clinical data were recorded from the electronic files and digital photographs of 99 patients with IH attending a tertiary pediatric medical center (2008-2011). Findings were evaluated by regression in volume and color changes. Results: The male-to-female ratio was 1:4. Age at treatment initiation was 9.4 ± 10.1 months; 15% of the treated hemangiomas were beyond the proliferative phase (17-54 months). The propranolol starting dose was 2 mg/kg/day. Duration of the treatment was 8.5 ± 3.2 months. All but 1 patient responded to treatment. A longer treatment course was required for segmental and deep hemangiomas. Mild side effects occurred in 32% of patients. Recurrence occurred in 13% of patients. Conclusion: Lesions located on the face are better responders when treatment is started early. Treatment should continue up to age 12-15 months, with a longer course for segmental or deep hemangiomas.

Pulse corticosteroid therapy for alopecia areata in children: a retrospective study.

Background/Objective: Alopecia areata may occur at any age, though usually before the age of 20 years. Treatment often consists of systemic steroids administered as high-dose bolus infusions. This study sought to investigate the effectiveness and side effects of intravenous high-dose pulse corticosteroids in children with alopecia areata and to identify prognostic factors for successful treatment. Methods: Patients treated with pulse corticosteroids for alopecia areata in 2001-2008 at the day care unit of a tertiary pediatric medical center were identified by computerized file search and clinical treatment and outcome data were collected. Results: The sample included 24 children (16 female, 8 male) with a mean age of 8.5 ± 4.6 years at diagnosis; 8 (33%) had multifocal disease,10 (42%) multifocal disease with ophiasis, 4 (17%) alopecia totalis and 2 (8%) alopecia universalis. Nail involvement was noted in 9 patients (38%). Mean duration of disease was 22 ± 27 months. Patients were treated with 8 mg/kg body weight intravenous methylprednisolone on 3 consecutive days at 1-month intervals. After a mean of 5.65 ± 1.95 courses, 9 patients (38%) had a complete response, 7 (29%) a partial response and 8 (33%) no response. Of the 16 responders, 13 (81%) relapsed at 9.5 ± 12 months after the last course; 3 patients had side effects, none of which were severe. Three positive prognostic factors were identified: short disease duration (≤6 months), younger age at disease onset (<10 years) and multifocal disease (as opposed to severe, diffuse variants). Conclusions: Careful patient selection is necessary to achieve maximal benefit from pulse corticosteroid treatment for alopecia areata in children.

Screening for Brain Involvement in Infants with Multifocal Cutaneous Infantile Hemangiomas

Background: Multifocal (≥5) infantile hemangiomas (IHs) are known as a risk factor for extracutaneous involvement. Liver is the most commonly involved organ, but involvement of other systems has also been reported. This study aims to describe the characteristic findings in a group of infants with multiple cutaneous hemangiomas, with emphasis on intracranial involvement. Methods: A retrospective case series study was carried out in a pediatric dermatology unit of a tertiary pediatric medical center. Patients diagnosed with multiple cutaneous IHs from 2006 to 2015 were identified by a computerized search. Clinical data were retrieved from the medical charts. Results: A total of 60 infants (37 females and 23 males) were identified for analysis. Forty-four brain ultrasounds were recorded and reported as normal. One patient out of the 44 was later diagnosed with a small asymptomatic hemangioma seen on a brain MRI/MRA done for another indication. Conclusion: Brain hemangiomas may present as an asymptomatic incidental finding in infants presenting with multifocal cutaneous and liver IHs. The single case reported in our study emphasizes the low prevalence and the benign course expected. Therefore, routine ultrasound screening for brain involvement is probably unnecessary for this population.