Objective. Juvenile localized scleroderma is a chronic progressive fibrotic disorder of the skin that causes permanent disability and aesthetic damage. This study was undertaken to assess the safety and efficacy of methotrexate (MTX) in the treatment of juvenile localized scleroderma.Methods. In this double-blind study, patients with active juvenile localized scleroderma were randomized (2:1) to receive oral MTX (15 mg/m 2 , maximum 20 mg) or placebo once weekly, for 12 months or until treatment failure. Both groups received oral prednisone (1 mg/kg/ day, maximum 50 mg) for the first 3 months. A target lesion was evaluated clinically, with infrared thermography and using a computerized scoring system with skin score rate (SSR) evaluation. Response to treatment was defined as the absence of new lesions, SSR <1, and a decrease in lesion temperature of at least 10% compared to baseline. Treatment failure was defined as the occurrence of new lesions, SSR >1, or increased lesion temperature. All analyses were done on the intent-totreat population.Results. Of the 85 patients screened, 70 (ages 6-17 years) were randomized (46 to the MTX group, 24 to the placebo group). The mean disease duration was 2.3 years. After an initial response in all patients, disease relapsed in 15 MTX-treated patients (32.6%) and 17 placebo-treated patients (70.8%) (P < 0.005). New lesions appeared in 3 MTX-treated patients (6.5%) versus 4 placebo-treated patients (16.7%). The mean SSR decreased from 1 to 0.79 in the MTX group and increased from 1 to 1.1 in the placebo group, and the mean target lesion temperature decreased by 44.4% in the MTX group versus 12.1% in the placebo group. Twenty-six patients in the MTX group (56.5%) and 11 patients in the placebo group (45.8%) developed mild side effects related to treatment. None of the side effects were severe enough to necessitate treatment discontinuation.Conclusion. Our findings indicate that MTX is efficacious in the treatment of juvenile localized scleroderma and is well tolerated.

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Background PIK3CA-related overgrowth spectrum (PROS) include a group of disorders that affect only the terminal portion of a limb, such as type I macrodactyly, and conditions like fibroadipose overgrowth (FAO), megalencephaly-capillary malformation (MCAP) syndrome, congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES) syndrome and Hemihyperplasia Multiple Lipomatosis (HHML). Heterozygous postzygotic PIK3CA mutations are frequently identified in these syndromes, while timing and tissue specificity of the mutational event are likely responsible for the extreme phenotypic variability observed.MethodsWe carried out a combination of Sanger sequencing and targeted deep sequencing of genes involved in the PI3K/AKT/mTOR pathway in three patients (1 MCAP and 2 FAO) to identify causative mutations, and performed immunoblot analyses to assay the phosphorylation status of AKT and P70S6K in affected dermal fibroblasts. In addition, we evaluated their ability to grow in the absence of serum and their response to the PI3K inhibitors wortmannin and LY294002 in vitro.Results and ConclusionOur data indicate that patients’ cells showed constitutive activation of the PI3K/Akt pathway. Of note, PI3K pharmacological blockade resulted in a significant reduction of the proliferation rate in culture, suggesting that inhibition of PI3K might prove beneficial in future therapies for PROS patients.

For many years the aetiology of neonatal occipital alopecia (NOA) has been reported to be friction. We have made a retrospective check to see if the incidence of NOA has increased since the new paediatric tendencies of putting children back to sleep in the safest way have been used (APP guidelines). The results of this study in 301 neonates demonstrated that it has not. The aetiology of this phenomenon is the physiological shedding of hair in the first weeks of life. The pillow, which is often blamed, only aids this shedding. Parents should be informed that there is no relationship between the sleep position and the onset of this problem, to prevent them from changing the position of the sleeping child, which could lead to a fatal outcome.

Eosinophilic cellulitis is an inflammatory skin disease with a broad spectrum of skin manifestations including cellulitic lesions sometimes associated with blisters, and rash with annular or circinate erythematous plaques. Peripheral eosinophilia (15%-67%) and diffuse dermal infiltrate of eosinophils with sub-epidermal oedema and 'flame figures' can be present. Although aetiology remains unknown, a type IV hypersensitivity reaction has been suggested. Triggering factors include infection, insect bites, hematologic disorders, drugs and vaccines. Cases of eosinophilic cellulitis reported after vaccinations have been attributed to thiomersal, neomycin or aluminium. 1,4 However, BNT162b2 vaccine does not contain these components.To our knowledge, this is the first case describing eosinophilic cellulitis associated with the vaccine against SARS-CoV-2. AcknowledgementThe patients in this manuscript have given written informed consent to the publication of their case details.