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Background: Leukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma gangrenosum (PG)-like skin ulcers (PGLUs) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1., Objective: Our aim was to report the case of a 10-year-old boy presenting with PGLUs as the first manifestation of LAD-1 treated with ustekinumab., Methods: We obtained in situ cytokine profiles., Results: PGLUs were triggered by cutaneous ringworm infection ( Trichophyton tonsurans ). Skin biopsy samples showed increased intralesional expression of IL-17A, Il-23, and IL-1β as compared with their expression in healthy controls. After an unsuccessful attempt at treatment with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile., Conclusions: PGLUs, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for patients with LAD-1 and PGLUs while bridging the time until stem cell transplantation., (© 2024 The Author(s).)

The purported antiviral effect of dupilumab may be considered a positive side effect. Its mechanism, however, points to an underlying immunomodulation with potentially far-reaching consequences., (© 2023 Wiley Periodicals LLC.)

Background: Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown., Objectives: To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition., Methods: Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data., Results: Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL., Conclusions: Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest: the authors declare they have no conflicts of interest.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair loss disorder characterized by coarse, wiry, and twisted hair developing during early childhood, and followed by progressive hair loss with puberty. We report a sporadic case of a 4-year-old boy with clinical features suggestive of MUHH, in whom we identified the new pathogenic variant c.67C>T; p.(Gln23*) in U2HR. This finding extends the known spectrum of U2HR variants underlying MUHH and increases genetic information for further genotype-phenotype correlation., (© 2023 Wiley Periodicals LLC.)

Background: Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity., Objective: Epidemiological data from different countries have been published, but none are available from Germany., Methods: In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization., Results: Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries., Conclusions: Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Competing Interests: Conflicts of interest None disclosed.

Vascular malformations (VMs) are caused by localized defects of vascular development. Most VMs are due to sporadic, postzygotic mutations, while some are the result of autosomal dominant germline mutations. Genotype-phenotype correlation is influenced by many factors. Individual genes can induce different phenotypes (pleiotropy), and similar phenotypes can be due to different genes/mutations (redundancy). The phenotypic spectrum of somatic mutations is wide, and depends on variant allele frequency, timing during embryogenesis, cell type(s) involved and type of mutation. The phenotype of germline mutations is determined by penetrance and expressivity, and is influenced by epigenetic factors (DNA methylation, histone modification) or 'second-hit' somatic mutations. Except for disorders with pathognomonic phenotypes such as Proteus syndrome or a characteristic constellation of symptoms such as CLOVES [congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal naevi and scoliosis/skeletal/spinal anomalies] or PIK3CA-related overgrowth spectrum syndrome, differential diagnosis of VM is therefore difficult. It will be greatly facilitated with increasing analytic sensitivity of sequencing techniques such as next-generation sequencing. High-sensitivity molecular techniques are a prerequisite for targeted pharmacotherapy, i.e. selective therapeutic inhibition of activating mutations underlying VM, which has shown promising results in preliminary studies., (© 2020 British Association of Dermatologists.)

Background: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear., Methods: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded., Results: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS., Conclusions: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Adalimumab (ADA) (Humira ® , AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis., Objectives: To evaluate the long-term efficacy and safety of ADA in children with severe plaque psoriasis., Methods: Results are presented from the 52-week long-term extension (LTE) of the randomized, double-blind, double-dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg -1 (40 mg maximum) or 0·4 mg kg -1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1-0·4 mg kg -1 (25 mg maximum) weekly. The 16-week initial treatment (IT) period was followed by a 36-week withdrawal period and a 16-week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg -1 (blinded or open label) or ADA 0·4 mg kg -1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods., Results: Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg -1 . Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31-86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28-47%; ADA 0·8(IT)/0·8(LTE) 50-72%. No serious infections occurred in the LTE., Conclusions: After 52 weeks of long-term ADA treatment in children aged 4-18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified. What's already known about this topic? The results from the first three periods of this phase III trial in children aged 4-18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population. What does this study add? This is the first study to evaluate long-term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population., (© 2019 The Authors British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: The proliferative phase of infantile hemangiomas (IHs) is usually complete by 9 months of life. Late growth beyond age 3 years is rarely reported., Objective: To describe the demographic and clinic characteristics of a cohort of patients with late growth of IH, defined as growth in a patient >3 years of age., Methods: A multicenter, retrospective cohort study., Results: In total, 59 patients, 85% of which were female, met the inclusion criteria. The mean first episode of late growth was 4.3 (range 3-8.5) years. Head and neck location (55/59; 93%) and presence of deep hemangioma (52/59; 88%) were common characteristics. Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome was noted in 20 of 38 (53%) children with segmental facial IH. Systemic therapy (corticosteroid or β-blocker) was given during infancy in 58 of 59 (98%) and 24 of 59 (41%) received systemic therapy (β-blockers) for late IH growth., Limitations: The retrospective nature and ascertainment by investigator recall are limitations of the study., Conclusion: Late IH growth can occur in children after 3 years of age. Risk factors include head and neck location, segmental morphology, and involvement of deep dermal/subcutaneous tissues., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

With a prevalence of 4·5%, infantile haemangiomas are the most common benign tumours of infancy, arising in the first few weeks of life and exhibiting a characteristic sequence of growth and spontaneous involution. Most infantile haemangiomas do not require therapy. However, to identify at-risk haemangiomas, close follow-up is crucial in the first weeks of life; 80% of all haemangiomas reach their final size by 3 months of age. The main indications for treatment are life-threatening infantile haemangioma (causing heart failure or respiratory distress), tumours posing functional risks (eg, visual obstruction, amblyopia, or feeding difficulties), ulceration, and severe anatomic distortion, especially on the face. Oral propranolol is now the first-line treatment, which should be administered as early as possible to avoid potential complications. Haemangioma shrinkage is rapidly observed with oral propranolol, but a minimum of 6 months of therapy is recommended., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background/objectives: Multifocal infantile hemangiomas (MIHs; previously called neonatal hemangiomatosis) can be associated with extracutaneous hemangiomas. We observed different morphologic types of hemangiomas in children with MIHs and sought to find out whether they are related to the clinical course., Methods: This was a retrospective study of 103 infants with MIHs and a control group of 261 age-matched patients with solitary focal infantile hemangiomas (IHs) seen at an academic pediatric dermatology department between 2004 and 2014., Results: Two morphologic subtypes of hemangiomas were identified: miliary focal hemangiomas (MFHs; small, lens shaped) in 58 of 103 MIH patients (56.3%), and classical nonmiliary focal IHs (NMIHs; larger, irregularly shaped) in 17 of 103 patients (16.5%). MIHs featuring both types (mixed type) were observed in 28 of 103 patients (27.2%). MFH lesions were significantly smaller (mean 5.3 mm [range 1-20 mm] vs 22.0 mm [range 2-100 mm]), more numerous (23.4 ± 27.3 [range 5-175] vs 7.4 ± 2.8 [range 5-15] p < 0.001), and occurred up to an older age (6.0 ± 5.8 months [range 0-27 months] vs 3.8 ± 2.6 months [range 0-9 months]) than NMIHs. There was a weakly positive correlation between the number and presence of extracutaneous IHs in children with MFHs. Significantly more children with MIHs were delivered preterm than those with solitary IHs., Conclusions: The number of IHs correlates inversely with their size. MFHs follow a clinical course different from that of classical IHs, are associated with prematurity, and may confer greater risk of extracutaneous hemangiomas. Miliary hemangiomas thus appear to present a separate IH subset requiring special attention., (© 2016 Wiley Periodicals, Inc.)

Background: From 18% to 30% of infantile hemangiomas (IH) are located on the extremities (IHE). They can be divided into localized, segmental, and minimal or arrested growth (IH-MAG) subtypes., Objective: We sought to correlate localization of IHE with the anatomy of the arterial vascular supply., Methods: All children with segmental IHE and IH-MAG presenting to our department of pediatric dermatology from 2002 to 2015 were evaluated. Hemangiomas were mapped and their patterns were analyzed., Results: Most IHE were unilateral (105/109). Two thirds (68/109) were located on the upper, and one third (41/109) on the lower extremities. Distal locations were more frequently affected. Segmental IHE were more common (upper extremities 83.8%; lower extremities 56.1%) than IH-MAG (16.2% and 43.9%, respectively). Ulceration occurred in 5.5%. Localization of IHE was found to correspond to supply areas of embryonic arterial variants., Limitations: This was a retrospective study. Only segmental IHE and IH-MAG were evaluated. Angiographic studies were not performed., Conclusion: The location of IHE may be related to variant anatomy of arterial supply during embryo fetal development. We hypothesize that this contributes to temporary regional tissue hypoxia during early fetal development, which is a known stimulus for the proliferation of hemangioma stem cells., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection., Methods: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids., Results: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]., Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres., Objectives: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs., Methods: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool., Results: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001., Conclusions: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study., (© 2015 British Association of Dermatologists.)

Background: Propranolol has become the first-line treatment for complicated infantile hemangiomas (CIHs) worldwide. Recommendations for monitoring infants undergoing propranolol therapy vary. Data on long-term blood pressure (BP) monitoring have not been reported before., Objective: The objective of the current study was to monitor BP in full-term infants during the induction and maintenance phase of propranolol therapy., Methods: BP was monitored prospectively in 109 infants (mean age 2.8 mos, range 1-5 mos) with CIHs during the induction (3-4 days in the hospital during up-dosing from 0.5 to 2.0 mg/kg/day) and maintenance (6 mos) phases of oral propranolol therapy., Results: Four children were excluded from the study because of sinus bradycardia (n = 2 [1.8%]) or lethargy (n = 2 [1.8%]). Mean systolic BP (SBP) decreased by 5 mmHg with the increase in propranolol dosage. Low (<5th percentile) SBP or diastolic BP (DBP) was observed in 2 of 105 children (1.9%) each. During the maintenance phase, 2 of 105 children (1.9%) had occasional SBP readings of less than 70 mmHg. No hypotension was observed after the third month of therapy. Low DBP (<36 mmHg) was recorded in 16 (15.2%) children after the first month, in 8.6% after the second, and in 2.9% during the third and fourth months of therapy. No patients exhibited clinical hypotension, bradycardia, or other known side effects of propranolol. Clinical response to therapy was excellent., Limitations: Reference BP values were derived from published tables, not from an untreated control group., Conclusions: In healthy full-term infants, propranolol (2 mg/kg/day divided in three doses) is well tolerated. No clinically significant hypotension was observed. We conclude that for otherwise healthy infants, BP monitoring during long-term propranolol therapy for CIHs is not necessary., (© 2015 Wiley Periodicals, Inc.)

Background: Safe and effective therapies are needed for pediatric patients with psoriasis., Objective: The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had moderate-to-severe psoriasis., Methods: Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg [≤60 kg], 45 mg [>60-≤100 kg], and 90 mg [>100 kg]) or half-standard dosing (HSD; 0.375 mg/kg [≤60 kg], 22.5 mg [>60-≤100 kg], and 45 mg [>100 kg]) at weeks 0 and 4 and every 12 weeks or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12. Clinical assessments included the proportion of patients achieving a Physician's Global Assessment of cleared/minimal (PGA 0/1), at least 75% improvement in Psoriasis Area and Severity Index (PASI 75), and at least 90% in PASI (PASI 90). Adverse events (AEs) were monitored through week 60., Results: At week 12, 67.6% and 69.4% of patients receiving ustekinumab HSD and SD, respectively, achieved PGA 0/1 versus 5.4% for placebo (P < .001). Significantly greater proportions receiving ustekinumab achieved PASI 75 (HSD, 78.4%; SD, 80.6%; placebo, 10.8%) or PASI 90 (HSD, 54.1%; SD, 61.1%; placebo, 5.4%) at week 12 (P < .001). Through week 12, 56.8% of placebo patients, 51.4% of HSD patients, and 44.4% of SD patients reported at least one AE; through week 60, 81.8% reported AEs., Limitations: The study was small relative to adult trials., Conclusions: In this patient population (12-17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: With a prevalence of 2.6-4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript., Conclusion: Oral propranolol is the first-line agent for the treatment of complicated IH., What Is Known: • Infantile haemangiomas (IH) are the most common tumours of infancy. Within a very short period after its discovery and long before the publication of randomized controlled trials, propranolol has become the number one agent for the treatment of complicated IH. What is New: • We report IH treatment recommendations of an international, interdisciplinary team of experts, based on an up-to-date review of the literature.

Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review., (© 2013 British Association of Dermatologists.)

Malignant cutaneous vascular tumours are very uncommon in children. As in adults, they are aggressive neoplasms with metastatic potential and a high mortality rate. Some nonmalignant vascular tumours may exhibit a locally aggressive behaviour and some of them can be associated with life-threatening systemic complications such as Kasabach-Merritt syndrome. Early diagnosis of these aggressive neoplasms in children is very important in order to start appropriate therapy as soon as possible, as this can have a significant impact on the prognosis of these patients. This review focuses on cutaneous vascular tumours of intermediate dignity (tufted angioma, kaposiform haemangioendothelioma, multifocal lymphangioendotheliomatosis with thrombocytopenia, papillary intralymphatic angioendothelioma, retiform haemangioendothelioma, adult-type haemangioendotheliomas) and malignant vascular tumours in young children (Kaposi sarcoma, angiosarcoma)., (© 2014 British Association of Dermatologists.)

Albright hereditary osteodystrophy (AHO) is a syndrome caused by inactivating mutations in the GNAS (guanine nucleotide-binding protein, alpha-stimulating) gene. Patients with AHO have short stature, obesity, brachydactyly and subcutaneous calcifications. AHO can be associated with pseudohypoparathyroidism type IA (PHP-IA) with upregulation of parathyroid hormone, whereas in pseudo-pseudohypoparathyroidism (PPHP), an endocrinopathy is not present. We report the case of a 5-month-old male infant who presented with slowly progressive linear atrophic skin lesions. The histological findings showed evidence of dermal hypoplasia. The child's father had PHP-IA. Four months after presentation, the infant developed calcifications within the pre-existent atrophic lesions. No alterations in calcium metabolism were noted. Analysis of the GNAS gene identified a short duplication leading to a frameshift mutation. We conclude that linear atrophic skin lesions may be an early sign of imminent cutaneous calcifications in AHO., (© The Author(s). CED © 2012 British Association of Dermatologists.)

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., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85-90% regress spontaneously, some may become life- or function-threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, alpha-interferon or cyclophosphamide, all bearing the risk of serious side-effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long-term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1-3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long-term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.

Atopic eczema in children usually responds to a management programme involving the regular use of emollients and the topical use of anti-inflammatory agents combined with patient education and the avoidance of environmental irritants or allergens (where necessary). If treatment fails, non-compliance should be considered first. Parents need to be reassured; a standardized educational program how to handle the disease with all its implications seems helpful. Persistent allergens or irritative triggers should be identified and eliminated. Systemic immunosuppression with either ciclosporin or azathioprine, mycophenolate mofetil or others should only be considered when parental compliance is warranted and all efforts have been made to eliminate external triggers. This article gives a short review on possible causes of treatment failures and ways to cope with them.

We report three cases of neonatal haemangiomatosis associated with large placental chorioangioma. Pregnancies were complicated by polyhydramnios, and all mothers underwent amniocentesis to drain the liquid. Steroid treatment was required for two children. Although the theory has been largely disproved in normal haemangiomas, embolization of precursor endothelial cells derived from placental vessels is a likely explanation for the pathogenesis of haemangiomatosis associated with large placental chorioangiomas.

Background: Cutis marmorata telangiectatica congenita (CMTC) is a congenital vascular anomaly of unknown aetiology. About 300 cases have been reported in the literature. The rate of associated anomalies varies between 20% and 70%., Methods: We report a series of 27 children with CMTC, 18 of whom were followed-up prospectively for a median of 22 months (range 2 months-5.3 years)., Results: Both genders were equally affected (13 male/14 female). The legs were involved in 20 cases (74%), the arms in 10 (37%), the face in 4 (15%) and the trunk in 18 (67%). There were 20 (74%) patients who presented with involvement of both trunk and limbs, a further 20 patients had lesions affecting the limb on only one side of the body, and 7 children (26%) had bilateral lesions; 1 child had generalized CMTC lesions. The involved areas covered a mean of 18% of body surface area (range 3-90). Associated anomalies were found in 15 patients (56%), with some exhibiting more than one. There was body asymmetry (hypertropy or hypotrophy of the affected limb) in nine patients (33%), seven patients had a variety of other malformations (congenital glaucoma, syndactyly, lipoma, macrocephaly, renal hypoplasia, Kartagener's syndrome), and other vascular lesions were present in four patients (15%). There was no correlation between the extent of skin lesions and likelihood of associated anomalies. On follow-up, fading of skin lesions was noted in 67% of our patients., Conclusion: Body asymmetry is the most common anomaly associated with CMTC; other associations might be pure chance. In order to separate CMTC from other vascular malformations, notably Klippel-Trénaunay syndrome, we suggest diagnostic criteria for their differentiation.