• 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.

MEDNIK syndrome-acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia-is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans-Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of copper metabolism with hypocupremia, hypoceruloplasminemia and liver copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver copper and bile-acid overload. We evaluated copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular copper metabolism and subcellular localization and function of copper pump ATP7A were investigated in patient fibroblasts. Copper metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal copper incorporation and retention, reduced expression of copper-dependent enzymes cytochrome-c-oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable by zinc acetate therapy, and can now be listed as a copper metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of copper pumps.

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents. In this Consensus, levels and models of intervention are also enriched by the Italian experience to facilitate a practical approach to the disease.

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations.Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.

A treatment algorithm as well as practical tools (i.e., tabular summaries of differential diagnoses, treatment mechanism of actions, dosing regimens, control parameters) are provided to assist in therapeutic reasoning and decision-making for individual patients. These treatment recommendations are endorsed by major Italian Pediatric and Dermatology Societies. What is Known: • Guidelines for the treatment of severe pediatric psoriasis are lacking and most traditional systemic treatments are not approved for use in young patients. Although there has been decades of experience with some of the traditional agents such as phototherapy, acitretin, and cyclosporine in children, there are no RCTs on their pediatric use while RCTs investigating new biologic agents have been performed. What is New: • In this manuscript, an Italian multidisciplinary team of experts focused on treatment recommendations for severe forms of psoriasis in children based on an up-to-date review of the literature and experts' opinions.

and Troilius Rubin created the Infantile Hemangioma Referral Score tool, selected the 42 clinical cases for validating the tool (stage 1), and validated the study design; Drs van der Vleuten and Roessler participated in the validation of the gold standard (stage 2); and all authors discussed and validated the study results (including the choice of the threshold), reviewed and validated the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

Familial hypercholesterolemia is an autosomal codominant disorder associated with markedly elevated plasma concentration of LDL-cholesterol and increased cardiovascular risk. Homozygous patients have rapid development of atherosclerosis with death from cardiovascular disease even in childhood. Life-long recurrent apheresis to reduce plasma LDL-cholesterol is considered the gold standard for treatment. Liver transplantation can be curative for this condition, but is usually only considered after the development of cardiovascular disease. We report a 5.5-yr-old child initially misdiagnosed with heterozygous familial hypercholesterolemia and treated by low-fat diet only. In view of persistent hypercholesterolemia and development of xanthomatosis, new molecular studies indicated the presence of two different mutations in the LDL receptor gene, with one being a deletion of two exons not identifiable with standard sequencing analysis. Recurrent plasma apheresis in combination with statins lowered, but did not normalize plasma LDL-cholesterol levels. It caused progressive reduction of the size of xanthomas and prevented the development of vascular complications. After two yr, liver transplantation normalized LDL-cholesterol levels and completely resolved the skin lesions. Preemptive liver transplantation is a definitive cure of familial homozygous hypercholesterolemia and might be more effective if performed before development of vascular complications.