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This article discusses the relationship between capillary malformations (CMs) and venous malformations, specifically focusing on the severity of venous malformations based on the type of associated CM. The study examined patients with segmental CMs and identified three groups based on the characteristics of their venous malformations. The findings suggest that ectatic deep veins and venous insufficiency, which are associated with a risk of pulmonary thromboembolism, may be more frequent and severe in cases of geographic CM. The study recommends investigating venous anomalies with Doppler ultrasound during follow-up to assess their specific risk. [Extracted from the article]

Summary: Background: Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis caused by a mutation in any one of five keratin genes (KRT6A,KRT6B,KRT6C,KRT16 or KRT17). Characteristic features of PC are painful palmoplantar keratoderma, variable nail dystrophy, cysts, follicular hyperkeratosis and often oral leukokeratosis. Although oral leukokeratosis can go unnoticed, mucosal involvement of the oral cavity and upper airways can manifest with pain during feeding, hoarseness, stridor and, occasionally, life‐threatening obstruction. Objectives: To characterize patients with PC with symptomatic mucosal involvement. Methods: We present a case series of nine children with PC with symptomatic mucosal involvement, all with heterozygous mutations in KRT6A. Seven patients complained of painful feeding problems. Four patients were diagnosed with failure to thrive, three of whom required a feeding tube. Simple feeding solutions were beneficial in most cases. Seven patients had laryngeal involvement and one patient died at 4 years of age from acute laryngeal obstruction. Conclusions: It is important for dermatologists and otolaryngologists to be aware that symptomatic mucosal involvement, and very rarely laryngeal obstruction, can occur in patients with PC. Usually simple feeding solutions may prevent complications and failure to thrive. What's already known about this topic? Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis due to a mutation in any one of five keratin genes.Symptomatic mucosal involvement is an important clinical feature of PC and appears to be more pronounced in KRT6A mutation carriers.Only leukokeratosis is frequently seen in PC and can be one of the earliest signs of disease.Laryngeal involvement is a less common feature. It might be symptomatic but usually presents as hoarseness, stridor and, occasionally, as a life‐threatening respiratory distress. What does this study add? In most cases of laryngeal involvement, there is no need for any intervention.Although pain and feeding difficulties are usually attributed to the oral leukokeratosis, they can be related to a phenomenon called 'first bite syndrome' (FBS).Symptomatic mucosal involvement with feeding difficulty is important but can be managed in most cases with simple feeding solutions (e.g. softer nipple with a larger hole, thicker formula and feeding with a syringe). Linked Comment:Youssefian and Vahidnezhad. Br J Dermatol 2020; 182:536–537. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa simplex ( EBS) is the most common form of EB. Eight different genes have been implicated in the pathogenesis of different types of EBS, but a substantial portion of the cases cannot be attributed to mutations in known genes. Recently, recessive mutations in the gene EXPH5 (encoding exophilin-5, also known as Slac2-b) were identified in patients affected with a mild form of EBS. We used immunohistochemistry, Sanger sequencing and PCR-restriction fragment length polymorphism analysis to identify the cause of mild congenital skin fragility in a 3-year-old girl. No mutations were detected in KRT5 or KRT14, but we identified a novel homozygous deletion in EXPH5, which was found to cosegregate with the disease phenotype in the family. Our results further expand the spectrum of mutations in EXPH5. Appraisal of the present case against previously reported patients indicate that EXPH5 mutations result in a distinctive skin fragility phenotype, with minimal blistering compared with other forms of basal EBS. [ABSTRACT FROM AUTHOR]

This article discusses the quantification of sweat volume in the pediatric population. The authors argue that while sweat volume is easily measurable, conditions such as hyperhidrosis and hypohidrosis are only defined qualitatively. By quantifying the mean volume of sweat in the general population, researchers can better define sweating disorders and assess the efficacy of treatments. The study extracted anonymous sweat volume information from a hospital's database and found that mean sweat volume remained constant between 6 months and 9 years of age, with no differences based on geographical origin or genetic background. The authors suggest routine sweat volume quantification to explore skin homeostasis and diseases of the eccrine sweat glands. [Extracted from the article]

Incidence rate and temporal trends in alopecia areata (AA) vary worldwide. As a common disorder with a major impact on life quality, there is a continuous need for comprehensive epidemiological characterization and global updates of the disease burden. We sought to perform an epidemiologic characterization of AA patients and to explore temporal trends across different subgroups using long-term health data. A retrospective population-based study was conducted in a large healthcare organization in Israel. Data were analyzed for all patients with AA between 2005 and 2019. A total of 30 805 patients for 29 504 798 person-years were identified during the study period, representing an overall incidence rate of 104.4 cases per 100 000 person-years. Young adults and patients of middle socioeconomic status had the highest incidence rate compared to the whole cohort. Incidence rates in females were lower than in males (incidence rate ratio 0.72, 95% confidence interval 0.71-0.74). In a temporal trends analysis, the yearly incidence rate for the whole cohort was stable throughout the study period. Males between the ages of 18 and 30 had a significant increase in incidence during the study years, where the incidence rate increased from 119.54 to 162.36 per 100 000 person-years. Despite the limitation of lack of analysis by subgroups of disease severity and other personal data, our study clearly indicates that young male adults of middle socioeconomic status emerge as the most at risk associated with AA over a decade and a half. In an effort to delineate risk factors for this gender gap, different stressors are speculated as triggers., (© 2023 Japanese Dermatological Association.)

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results., (© 2023 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date., Methods: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds., Results: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001)., Conclusions: EB patients of Middle Eastern origin were found to feature specific phenotype-genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region., (© 2023 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Purpose: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit., Methods: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate., Results: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10)., Conclusion: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

Competing Interests: Conflicts of interest None disclosed.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation., (© 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Generalized acquired dermatoses can seldom manifest more prominently or exclusively along the lines of Blaschko. Six individuals with segmental atopic dermatitis (AD) have been reported to date. We present three additional cases of segmental cutaneous manifestations superimposed on generalized AD, and review the relevant literature., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation., Methods: We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT., Results: Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period., Conclusions: FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction: Whether individuals with atopic diseases have a different risk of contact allergy compared to those who are non-atopic is controversial and data are conflicting., Aim: To explore the association between atopy and allergic contact dermatitis (ACD)., Material and Methods: This retrospective cross-sectional study included 301 patients referred to a tertiary clinic to evaluate ACD. Demographic details including personal and familial mucosal or cutaneous atopic status were recorded. Patch tests were tailored to their clinical presentations and relevant exposures., Results: At least 1 positive patch test reaction was observed in 177 patients (59% of the study cohort), of which 52% had a history of atopic diseases, compared with 44% of patients with a negative patch test result ( p = 0.2). Additionally, 147 patients had an atopic background, of which 92 (62%) had ≥ 1 positive patch test result, compared with 55% of non-atopic patients ( p = 0.2). Nickel sulphate was the most common contact allergen (13.4% of the patch test reactions)., Conclusions: We identified a positive tendency for atopic diseases among individuals with ACD and vice versa. Our study supports the aggregate data from previous studies despite the non-significant differences between the study and control groups. However, further research performed in larger populations of patients is necessary to evaluate the real association between atopy and ACD on a solid basis. Our results indicate the necessity of systematic patch testing in patient setups with atopic background and chronic dermatitis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Background: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications., Objective: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma., Methods: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs., Results: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods., Conclusion: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome., (© 2021 Wiley Periodicals LLC.)

Background: Melasma is a complex and poorly understood disorder, with high rates of treatment failure and recurrences., Objectives: We aimed to review the current knowledge of the pathogenesis of melasma and apply this knowledge to clinical implications on relevant therapeutic interventions., Methods: A systematic PubMed search was performed using the search term "((melasma[Text Word]) OR facial melanosis[Text Word]) AND (pathogenesis OR causality[MeSH Terms])" for articles published between 1990 and 2020. Included articles were then evaluated by two authors and assessed for relevant pathomechanistic pathways, after which they were divided into groups with minimal overlap. We then reviewed current treatment modalities for melasma and divided them according to the involved pathomechanistic pathway., Results: A total of 309 search results were retrieved among which 76 relevant articles were identified and reviewed. Five main pathomechanisms observed in melasma were identified: (1) melanocyte inappropriate activation; (2) aggregation of melanin and melanosomes in dermis and epidermis; (3a) increased mast cell count and (3b) solar elastosis; (4) altered basement membrane; and (5) increased vascularization. Treatment modalities were then divided based on these five pathways and detailed in 6 relevant tables., Conclusion: The pathophysiology of melasma is multifactorial, resulting in treatment resistance and high recurrence rates. This wide variety of pathomechanisms should ideally be addressed separately in the treatment regimen in order to maximize results., (© 2021 Wiley Periodicals LLC.)

The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20-85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population.

Autosomal recessive congenital ichthyosis (ARCI) is a rare and heterogeneous skin cornification disorder presenting with generalized scaling and varying degrees of erythema. Clinical manifestations range from lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) through the most severe form of ARCI, Harlequin ichthyosis (HI). We used homozygosity mapping, whole-exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotype-phenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI-associated genes including TGM1 (21%), CYP4F22 (18%), ALOX12B (14%), ABCA12 (10%), ALOXE3 (6%), NIPAL4 (5%), PNPLA1 (3%), LIPN (2%) and SDR9C7 (2%). In 19% of cases, no mutation was identified. Our cohort revealed a higher prevalence of CYP4F22 and ABCA12 pathogenic variants and a lower prevalence of TGM1 and NIPAL4 variants, as compared to data obtained in other regions of the world. Most variants (89%) in ALOX12B were associated with CIE and were the most common cause of ARCI among patients of Muslim origin (26%). Palmoplantar keratoderma associated with fissures was exclusively a result of pathogenic variants in TGM1. To our knowledge, this is the largest cohort study of ARCI in the Middle-Eastern population reported to date. Our data demonstrate the importance of population-tailored mutation screening strategies and shed light upon specific genotype-phenotype correlations., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cutaneous manifestations of dedicator of cytokinesis 8 gene (DOCK8) deficiency, a combined type of T and B cell immunodeficiency, previously designated as autosomal recessive hyper IgE syndrome, includes dermatitis and skin infections. There are limited treatment options for dermatitis related to the syndrome., Objective: To describe a cohort of patients with DOCK8 deficiency with a focus on the treatment of their cutaneous manifestations., Methods: A retrospective study on all children with the genetic diagnosis of DOCK8 deficiency treated at the Sheba Medical Center between 1/1/2003 and 1/1/2021 was preformed. Collected data included: demographic features, family history, laboratory, genetic testing, skin manifestations, treatment, and disease course. Description of two cases of severe recalcitrant dermatitis treated with dupilumab is detailed., Results: Nine children with a genetic diagnosis of DOCK8 deficiency were included, of whom six were girls (66%) with a median age of 8.5 (±2.2 SD) years. The median age at diagnosis was 2.8 (±2.6 SD) years. Six patients were born to consanguineous parents. Five out of six patients who received hematopoietic stem cell transplantation (HSCT) had a complete response, and one was recently transplanted. Of note, two patients, while awaiting HSCT, were treated with dupilumab for their severe dermatitis resulting in a marked improvement of the cutaneous manifestations and pruritus., Conclusions: Hematopoietic stem cell transplantation is the gold standard and most effective therapy for patients with DOCK8 deficiency. Dupilumab, a biological therapy indicated for atopic dermatitis and other Th2 derived dermatoses, is an excellent option for dermatitis in patients with DOCK8 deficiency and can be used as a bridge before HSCT. Larger studies are needed to confirm this observation., (© 2021 Japanese Dermatological Association.)

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis ( n = 122) and healthy subjects ( n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7-86.3%) and specificity of 80.2% (95% CI, 76.1-84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.

Griseofulvin and terbinafine are considered effective first-line therapies for tinea capitis (TC). Haematological dyscrasias and hepatic injury are possible adverse effects with both drugs. There is a debate in the literature regarding the necessity of laboratory monitoring during griseofulvin and terbinafine treatment. We aimed at assessing the prevalence and severity of haematological and hepatic laboratory test abnormalities in a paediatric cohort of African immigrants in Tel-Aviv with TC who were treated with Terbinafine or Griseofulvin. We conducted a retrospective study of all TC cases diagnosed and treated at the paediatric dermatology clinic, Tel-Aviv Medical centre, between June 2013 and March 2019. Epidemiologic, clinical and laboratory data were collected. Our cohort included 321 patients of whom 225 (70%) were treated with Griseofulvin and 96 (30%) with Terbinafine. We identified a total of 64 (20%) patients with haematological or hepatic laboratory test abnormalities that in most cases (96.3%) were considered as mild. No difference in laboratory abnormalities prevalence was identified between the griseofulvin and terbinafine groups (21.3% and 16.6%, respectively). Only one patient treated with Griseofulvin revealed significantly increased levels of hepatic aminotransferases that required discontinuation of treatment. Mild elevation in hepatic transaminases is relatively common among paediatric patients treated with systemic antifungal treatment for TC. However, significant laboratory abnormalities are extremely rare and may be diagnosed and addressed early through periodic laboratory tests monitoring., (© 2020 Wiley-VCH GmbH.)

BACKGROUND Right-sided endocarditis is a well-known condition that occurs predominantly in intravenous drug users and patients with cardiovascular implantable electronic devices, central venous lines, and congenital heart disease. Most cases involve the tricuspid valve apparatus. Eustachian valve endocarditis (EVE) is a very rare and underdiagnosed condition with only a few previously reported cases. CASE REPORT We present a rare case of 2-sided infective thromboembolism from Staphylococcus aureus endocarditis involving both the eustachian and mitral valves in a 27-year-old man with mitochondrial neurogastrointestinal encephalopathy disease, which is a rare mitochondrial disease. CONCLUSIONS Endocarditis involving the eustachian valve is rare and presents a significant dilemma in diagnosis and treatment. Late diagnosis can lead to missed thromboembolic events and can have a significant impact on treatment and prognosis. In cases with high suspicion, early use of transesophageal echocardiography and chest CT can greatly advance diagnosis. The international guidelines do not specifically address patients with EVE; therefore, we recommend that the endocarditis team should be involved in any case of EVE to customize a treatment strategy.

Background: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs., Objective: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH., Methods: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed., Results: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported., Limitations: This is an uncontrolled retrospective study., Conclusion: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH., (© 2020 S. Karger AG, Basel.)

Successful treatment of Hailey-Hailey disease with intradermal botulinum toxin injections has been previously reported. The main disadvantages of this treatment are the excruciating pain and the risk of infections due to the numerous injections. We sought to evaluate the clinical effectiveness and safety profile of a novel approach using an energy-based device (Tixel, Novoxel, and Israel), followed by the topical application of botulinum toxin Type A for the treatment of Hailey-Hailey disease. A retrospective study of all cases of histologically diagnosed cases of Hailey-Hailey disease treated with Tixel device followed by topical application of botulinum toxin between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. The study included eight patients, of whom seven patients (87.5%) showed good or partial response. No systemic or local adverse effects were reported. There was no difference in effectivity between different body areas. Response to treatment ranged between patients with an average duration of 7.125 months after the second treatment. Tixel treatment followed by topical application of botulinum toxin can be considered in the treatment of Hailey-Hailey disease. This approach is less invasive, less painful, and yet effective as well as safe., (© 2019 Wiley Periodicals, Inc.)

Background: Pediatric hypertrophic burn scars are challenging to treat due to their widespread nature and pain associated with the treatment. Intralesional triamcinolone acetonide (TAC) injection with or without 5-fluorouracil (5FU) is considered first-line treatment for severe hypertrophic scars. The pain associated with the procedure, the uneven topography, and epidermal atrophy, all limit the application of this treatment modality., Aims: We sought to evaluate the clinical effectiveness and safety profile of a novel thermomechanical system (Tixel, Novoxel) for transdermal delivery of a topical solution containing TAC and 5-FU in the treatment of hypertrophic scars., Patients/methods: A retrospective study of pediatric hypertrophic burn scars treated between 2015 and 2017 was performed. Epidemiologic, treatment data, effectiveness score, and safety were reviewed., Results: Four children (one male and three females, ages 3-10 years old) with hypertrophic burn scars treated with the Tixel device were evaluated. Mean scar VSS was reduced from 8.4 ± 0.8-5.2 ± 0.5 (P-value - .001) after eight treatments. The mean improvement of toughness, thickness, color, and general aesthetic impression was 3.1 ± 0.43 → 2.2 ± 0.31, 3.4 ± 0.5 → 1.9 ± 0.63, 2.7 ± 0.21 → 2.4 ± 0.25, and 3.23 ± 0.44 → 1.6 ± 0.64, respectively. Mean treatment pain VAS score was 1.74 ± 0.9. Patient's parents rated their satisfaction level as "moderate-high." No topical or systemic complications were observed., Conclusion: Thermomechanical decomposition of the stratum corneum, in combination with topical application of TAC and 5-FU, is a safe, relatively painless, and efficient modality for the treatment of pediatric hypertrophic burn scars., (© 2019 Wiley Periodicals, Inc.)

Although pulsed dye laser (PDL) is considered the gold standard treatment for port wine stains (PWS), post PDL revascularization is one of the main causes of incomplete regression and recurrence. Recently, topical sirolimus have been shown to improve treatment outcome probably through minimizing post-laser revascularization. We sought to evaluate the added value of the Tixel drug delivery system (DDS) to the PDL and topical rapamycin treatment for PWS. This case series includes three teenager patients with previously treated PWS with PDL. Upon enrollment, every stain was divided into A and B halves for treatment assignments to the following regimens: (A) PDL + DDS + rapamycin; (B) PDL + rapamycin. Subjects were instructed to apply rapamycin topically over the PWS twice daily for the entire treatment period. Assessment of the treatment and adverse reactions as well as photographs was performed at baseline and before every PDL treatment. There were clinically significant differences in blanching responses favoring PWS receiving PDL + DDS + rapamycin as compared to PDL + rapamycin alone. Transient hyperpigmentation was noted in one patient. Two patients developed mild transient irritation and dermatitis following the treatment on both halves. The use of drug delivery system combined with topical rapamycin has no remarkable adverse effects, improves the results of PDL treatment for port wine stains, and can reduce the total number of required PDL sessions., (© 2019 Wiley Periodicals, Inc.)

Outbreaks of tinea capitis (TC) can be a source of medical and economic burden for healthcare systems; Griseofulvin and terbinafine are considered to be effective first-line treatments for TC. In order to compare the efficacy of griseofulvin and terbinafine for the treatment of TC in a paediatric population of African immigrants in the Tel Aviv area, we conducted a retrospective cohort study of all cases of TC diagnosed and treated between March 2016 and February 2018 at a dedicated TC paediatric dermatology clinic at the Tel Aviv Medical Center (which serves as a referral centre for the paediatric refugee population in the Tel Aviv metropolitan area). Epidemiologic, clinical and laboratory data were collected, and 304 patients were included. Trichophyton violaceum (TV), Trichophyton soudanense (TS) and Microsporum audouinii (MA) were the prominent causative organisms. Treatment with griseofulvin suspension for 12 weeks was compared with (a) griseofulvin suspension for 8 weeks and with (b) terbinafine tablets for 4 weeks. There was no statistically significant difference between the groups regarding age, sex, country of birth, ethnicity and the causative organism. Twelve weeks of griseofulvin treatment had a statistically significant better cure rate than 4 weeks of terbinafine. Treatment was significantly more effective when TC was due to infections with MA and TS as compared with TV. No statistically significant difference was observed between 12- and 8-week treatment with griseofulvin., (© 2019 Blackwell Verlag GmbH.)

Pyogenic granuloma is a benign acquired vascular tumor that affects the skin and mucous membranes, occurring more often in children and young adults. Treatment is often required due to the associated risk of ulceration and bleeding. There are several publications reporting the use of beta-blockers for the treatment of pyogenic granuloma. The aim of the present study was to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of pyogenic granuloma. A retrospective study of all cases of pyogenic granuloma treated with topical propranolol 4% gel between 2014 and 2015 was performed. Epidemiological, clinical and treatment data, including effectiveness score and safety, were reviewed. Of a total of 18 patients with pyogenic granuloma, 11 (61.1%) showed complete resolution of the lesion while two (11.1%) had an almost complete response. In three cases (16.6%), the treatment was discontinued due to bleeding, and the lesions were removed by curettage. Local irritation and lack of compliance led to treatment discontinuation in two cases. Altogether, 13 out of 18 patients (72%) had complete or almost complete response to treatment. There was a correlation between treatment duration and response to treatment. One patient only reported local side-effects including irritation, redness and scaling of the treated area leading to discontinuation of the treatment and curettage of the pyogenic granuloma. No systemic adverse effects were reported. This is an uncontrolled retrospective study. Propranolol 4% gel may be considered as a safe and efficient topical therapy for pyogenic granuloma., (© 2018 Japanese Dermatological Association.)

Background: Leishmaniasis is a protozoan zoonotic parasitic infection with cutaneous, mucocutaneous, and visceral manifestations. Israel is endemic for cutaneous leishmaniasis, which is a self-limited disease but is associated with scarring, which is often a source of psychological and social burden for patients. Scars can be especially devastating for children and teenagers. A wide range of physical and medical approaches is used to treat cutaneous leishmaniasis, among which intralesional injections of sodium stibogluconate rank among the most frequently used. Unfortunately, despite being effective, this therapeutic modality can be very painful. Fractional ablative laser creates a controlled mesh-like pattern of tissue ablation in the skin that promotes dermal remodeling and collagen production while at the same time facilitating enhanced delivery of topically applied medications., Methods: Patients were treated with fractional ablative carbon dioxide laser followed by immediate topical application of sodium stibogluconate. All children were diagnosed with cutaneous leishmaniasis prior to treatment initiation.., Results: Ten children were treated. One leishmania tropica-positive girl failed to respond. The other nine patients achieved clinical cure and demonstrated good to excellent final cosmesis. Self-rated patient satisfaction and tolerance were high No adverse effects were observed or reported during treatment., Conclusion: Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application appears to be a safe and promising treatment for cutaneous leishmaniasis infection in children. Future controlled studies are required to validate these findings and compare this technique with traditional approaches., (© 2018 Wiley Periodicals, Inc.)

Background: Although isolated cafe-au-lait macules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1)., Objective: We sought to develop an algorithm determining the risk of children with CALMs to have constitutional NF1., Methods: We conducted a retrospective study of patients with isolated CALMs. Diagnosis of NF1 was based on detecting NF1 mutation in blood or fulfilling clinical criteria., Results: In all, 170 of 419 (41%) and 21 of 86 (24%) children with isolated CALMs who underwent molecular testing and clinical follow-up, respectively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atypical CALMs was associated with not having NF1 (P < .001). An algorithm based on age, CALMs number, and presence of atypical macules predicted NF1 in both cohorts. According to the algorithm, children older than 29 months with at least 1 atypical CALM or less than 6 CALMs have a 0.9% (95% confidence interval 0%-2.6%) risk for constitutional NF1 whereas children younger than 29 months with 6 or more CALMs have a high risk (80.4%, 95% confidence interval 74.6%-86.2%)., Limitations: The study was designed to detect constitutional NF1 and not NF1 in mosaic form., Conclusions: A simple algorithm enables categorization of children with isolated CALMs as being at low or high risk for having NF1., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs., Objective: We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs., Methods: A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed., Results: The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported., Limitations: This is an uncontrolled retrospective study., Conclusion: Propranolol 4% gel is a safe and efficient topical therapy for IH., (© 2017 The International Society of Dermatology.)

Background/objectives: Molluscum contagiosum (MC) is a common viral disease primarily affecting children. The objective was to compare the effectiveness of curettage as a treatment modality for MC with no treatment., Methods: We performed a retrospective study of 2,022 children with MC between 2008 and 2012. Epidemiologic, clinical, and treatment data, including effectiveness, safety, and satisfaction, were reviewed., Results: Fifty-six percent of the children were 2 to 5 years of age. The duration of the infection was 1 to 2 years for 51%, less than 1 year for 32%, and more than 2 years for 17% of the children. Seventy percent of the children were self-referrals; 86% had had a previous examination and 76% of those had been advised not to treat the infection. The disease was mild (22%), moderate (64%), or severe (14%). A total of 1,879 patients underwent curettage; 70% were cured after one treatment and 26% after two treatments. Satisfaction was high: 97% of children and parents., Conclusion: Active treatment should be offered despite the fact that MC is self-limiting. Curettage in an appropriate setting is very effective, with high patient satisfaction and fast cure rates., (© 2016 Wiley Periodicals, Inc.)

Outbreaks of tinea capitis (TC) represent a major medical and economic burden. Population migrations have become a phenomenon of increasing relevance for medical conditions management. Given the recent massive arrival of immigrants, we sought to determine epidemiologic trends for TC among paediatric populations at the Tel Aviv Medical Center. We conducted a retrospective study of all TC cases diagnosed between 2010 and 2014 in a paediatric dermatology unit of a tertiary medical centre, serving as a referral centre for the paediatric refugee population from the great Tel Aviv area. Epidemiologic, clinical and treatment data including effectiveness and safety were reviewed. In all, 145 children met the inclusion criteria. Trend analyses showed increases in TC rates over the study period. Incidence rates were higher in boys than in girls. Children of African origin had the highest TC incidence rates as compared with other ethnic groups. Trichophyton violaceum and Microsporum audouinii were the predominant causative organisms. Treatment with griseofulvin was satisfactory in all cases. There was a significant increase in TC incidence rates in the Tel Aviv area over the study period. TV and MA were the predominant organisms. These trends may be a result of poor living conditions and crowded school premises., (© 2016 Blackwell Verlag GmbH.)