Cost-utility analysis of propranolol versus corticosteroids in the treatment of proliferating infantile hemangioma in Italy

Objectives Infantile hemangioma (IH) is the most common childhood benign tumour. A recent phase II/III study has demonstrated the success of propranolol for involution of infantile hemangioma as well as a better efficacy and safety when indirectly compared with corticosteroids. The purpose of this study was to estimate the cost-utility of propranolol (Hemangiol), a new medicinal product and the first to be authorized for this specific paediatric indication, versus corticosteroids in the treatment of proliferating infantile hemangioma requiring systemic therapy

Amyloid Oligomer Neurotoxicity, Calcium Dysregulation, and Lipid Rafts

Amyloid proteins constitute a chemically heterogeneous group of proteins, which share some biophysical and biological characteristics, the principal of which are the high propensity to acquire an incorrect folding and the tendency to aggregate. A number of diseases are associated with misfolding and aggregation of proteins, although only in some of them—most notably Alzheimer's disease (AD) and transmissible spongiform encephalopathies (TSEs)—a pathogenetic link with misfolded proteins is now widely recognized. Lipid rafts (LRs) have been involved in the pathophysiology of diseases associated with protein misfolding at several levels, including aggregation of misfolded proteins, amyloidogenic processing, and neurotoxicity. Among the pathogenic misfolded proteins, the AD-related protein amyloid β (Aβ) is by far the most studied protein, and a large body of evidence has been gathered on the role played by LRs in Aβ pathogenicity. However, significant amount of data has also been collected for several other amyloid proteins, so that their ability to interact with LRs can be considered an additional, shared feature characterizing the amyloid protein family. In this paper, we will review the evidence on the role of LRs in the neurotoxicity of huntingtin, α-synuclein, prion protein, and calcitonin

Frequent Occurrence of Aplasia Cutis Congenita in Bullous Dermolysis of the Newborn.

Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis bullosa characterized by rapid improvement in skin fragility within the first months of life, associated with typical immunofluorescence and ultrastructural features. Inheritance can be autosomal dominant or recessive. We report here 4 cases of BDN, 2 of which presented with aplasia cutis congenita of the lower extremities. All patients improved rapidly and blister formation ceased by the third month of life in 3 cases. In these patients only residual milia, nail dystrophies and atrophic scarring at sites of aplasia cutis were visible by one year. Family history indicated dominant inheritance in 2 cases, confirmed by identification of COL7A1 mutation. Molecular analysis also revealed recessive inheritance in the 2 sporadic cases. A literature search identified several patients with BDN born with skin defects localized to the lower extremities. In conclusion, these findings indicate that aplasia cutis congenita is not an infrequent manifestation of BDN

Lipoid Proteinosis: A Previously Unrecognized Mutation and Therapeutic Response to Acitretin.

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Ichthyosis with confetti: clinics, molecular genetics and management

Ichthyosis with confetti (IWC) is an autosomal dominant congenital ichthyosis also known as ichthyosis variegata or congenital reticular ichthyosiform erythroderma. It manifests at birth with generalized ichthyosiform erythroderma or with a collodion baby picture. The erythrodermic and ichthyotic phenotype persists during life and its severity may modify. However, the hallmark of the disease is the appearance, in childhood or later in life, of healthy skin confetti-like spots, which increase in number and size with time. IWC is a very rare genodermatosis, with a prevalence <1/1,000,000 and only 40 cases reported worldwide. The most important associated clinical features include ear deformities, mammillae hypoplasia, palmoplantar keratoderma, hypertrichosis and ectropion. IWC is due to dominant negative mutations in the KRT10 and KRT1 genes, encoding for keratins 10 and keratin 1, respectively. In this context, healthy skin confetti-like spots represent “repaired” skin due to independent events of reversion of keratin gene mutations via mitotic recombination. In most cases, IWC clinical suspicion is delayed until the detection of white skin spots. Clinical features, which may represent hint to the diagnosis of IWC even before appearance of confetti-like spots, include ear and mammillae hypoplasia, the progressive development of hypertrichosis and, in some patients, of adherent verrucous plaques of hyperkeratosis. Altogether the histopathological finding of keratinocyte vacuolization and the nuclear staining for keratin 10 and keratin 1 by immunofluorescence are pathognomonic. Nevertheless, mutational analysis of KRT10 or KRT1 genes is at present the gold standard to confirm the diagnosis. IWC has to be differentiated mainly from congenital ichthyosiform erythroderma. Differential diagnosis also includes syndromic ichthyoses, in particular Netherton syndrome, and the keratinopathic ichthyoses. Most of reported IWC cases are sporadic, but familial cases with autosomal dominant mode of inheritance have been also described. Therefore, knowledge of the mutation is the only way to properly counsel the couples. No specific and satisfactory therapy is currently available for IWC. Like for other congenital ichthyoses, topical treatments (mainly emollients and keratolytics) are symptomatic and offer only temporary relief. Among systemic treatments, retinoids, in particular acitretin, improve disease symptoms in most patients. Although at present there is no curative therapy for ichthyoses, treatments have improved considerably over the years and the best therapy for each patient is always the result of both physician and patient efforts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0336-4) contains supplementary material, which is available to authorized users

Early immunopathological diagnosis of ichthyosis with confetti in two sporadic cases with new mutations in keratin 10.

Ichthyosis with confetti (IC) is a severe non-syndromic ichthyosis due to heterozygous mutations in the KRT10 gene. The disease manifests at birth with erythroderma and scaling and is characterised by the gradual development of numerous confetti-like spots of normal skin. Diagnosis of IC is frequently delayed until adolescence or even adulthood. We report 2 young children who were first diagnosed as having congenital ichthyosiform erythroderma. However, the development of thick, confluent hyperkeratotic plaques together with the histopathological finding of keratinocyte vacuolisation in the suprabasal epidermis evoked IC. Immunofluorescence analysis showed a highly reduced keratin 10 expression within the cytoplasm of suprabasal keratinocytes and its characteristic mislocalisation to the nuclei. The diagnosis was confirmed by the identification of 2 previously unreported mutations in intron 6 and exon 7 of KRT10. Careful clinical examination then showed the presence of the first spots of normal skin in both patients at the age of 2.5 and 5 years, respectively. These cases point to the usefulness of immunofluorescence analysis of keratin 10 expression for an early diagnosis of IC

Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis

BACKGROUND: The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. Mutations in a broad group of genes related to keratinocyte differentiation and epidermal barrier function have been demonstrated to play a causative role in disease development. Ichthyosis may be classified in syndromic or non-syndromic forms based on the occurrence or absence of extracutaneous signs. In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing. METHODS: Due to the complex features of the different ichthyoses and the high number of genes involved we have investigated a group of 64 patients, affected by syndromic and non-syndromic diseases, using Next Generation Sequencing as a new tool for the molecular diagnosis. RESULTS: Using this innovative molecular approach we were able to find pathogenic mutations in 53 out of 64 patients resulting in 82.8 % total detection rate. An interesting result from the analysis of the data is the high rate of novel sequence variations found compared to known mutations and the relevant rate of homozygous mutations. CONCLUSIONS: The possibility to analyze a large number of genes associated with various diseases allows to study cases with phenotypes not well-determined, giving the opportunity to make new genotype-phenotype correlation. In some cases there were discrepancies between clinical features and histology or electron microscopy and only molecular analysis allowed to definitively resolve the diagnostic dilemma. The genetic diagnosis of ichthyosis leads to a more accurate and effective genetic counseling, allowing correct evaluation of the risk of recurrence, particularly in families with consanguineous background. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-016-0384-4) contains supplementary material, which is available to authorized users