We have recently noticed an outbreak of chilblain-like lesions in Italy contemporarily to COVID-19 epidemic. Due to the wellknown lockdown-related difficulties to visit the patients, 1 we created a Google form aimed to collect information about patients presenting with these singular clinical findings. An easy to access and quick tool was chosen by the investigators in order to permit the other colleagues to spend the least amount of time, given the severe health emergency. The form was submitted through social media and email to hundreds of Italian dermatologists and paediatricians. In 5 days, we collected 63 patients through the form, but data are still going to be collected. Here the first preliminary results. No significant difference in gender was noticed (57.4% females vs 47.6% males). The median age was 14 years (IQR: 12-16). Feet alone were mostly affected (85.7%) followed by feet/hands together (7%) and hands alone (6%). Pictures of patients were uploaded in 54 patients, with 31/ 54 presenting with erythematous-oedematous lesions (Fig. 1) and 23/54 with blistering lesions (Fig. 2). Pain and itch were equally observed (27% vs. 27%), followed by pain/itch together shown in 20.6% of patients. Asymptomatic lesions were present in 25.4%. Median time from the onset to clinical diagnosis was 10 days (IQR: 6-15). At time of diagnosis, most patients pre-

Background SAPHO (synovitis, acne, pustolosis, hyperostosis and osteitis) syndrome is a rare autoinflammatory chronic disorder, presenting with non-infectious osteitis, sterile joint inflammation and skin manifestations including palmoplantar pustolosis and severe acne. It could be often misdiagnosed for its heterogeneous clinical presentation. Treatment is challenging and, due to the rarity of this syndrome, no randomized controlled clinical trials have been conducted. Empirical treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibiotics and bisphosphonates and disease-modifying anti-rheumatic drugs (DMARDs) could be quite effective. Anti-tumor necrosis factor-alpha (anti-TNF-α) agents and interleukin-1 (IL-1) antagonists have shown promising results in refractory patients. Isotretinoin, commonly used for severe acne, has been rarely described as possible trigger of osteo-articular manifestations, in particular sacroiliitis. Case presentation The case of a boy, affected by acne fulminans and depression, who presented with sacroiliitis after a 10-week treatment with isotretinoin is presented. After SAPHO diagnosis, NSAIDs therapy was started but the onset of bilateral gluteal hidradenitis suppurativa required the switch to a TNF-α antagonist (Adalimumab) with the achievement of a good control of the disease. Despite specific therapy with sertraline, the patient continued to complains severe depression. Conclusions Our case reports a temporal association between the onset of osteo-articular symptoms and the introduction of isotretinoin, as previously described. However, this timeline is not sufficient to establish a causal role of this drug into the pathogenesis of sacroiliitis. At this regard, further studies are required. The occurrence of hidradenitis suppurativa during SAPHO course supported the introduction of TNF-α blockers with a favourable result, as reported in a few cases in literature. The association between SAPHO syndrome and depressive mood disorders is already reported. Our patient experienced severe depression whose trend seems to be independent from the course of the main disease. Currently, it is not clarified if depression could be considered reactive to the underling disease or if it forms an integral part of the autoinflammatory disorder.

Corticosteroids are the mainstay of therapy for many pediatric disorders and sometimes are life-saving. Both endogenous and synthetic derivatives diffuse across the cell membrane and, by binding to their cognate glucocorticoid receptor, modulate a variety of physiological functions, such as glucose metabolism, immune homeostasis, organ development, and the endocrine system. However, despite their proved and known efficacy, corticosteroids show a lot of side effects, among which growth retardation is of particular concern and specific for pediatric age. The aim of this review is to discuss the mechanism of action of corticosteroids, and how their genomic effects have both beneficial and adverse consequences. We will focus on the use of corticosteroids in different pediatric subspecialties and most common diseases, analyzing the most recent evidence.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term referring to various clinical entities, which share the same pathogenetic mechanism. These conditions are caused by somatic gain-of-function mutations in PIK3CA, which encodes the 110-kD catalytic α subunit of PI3K (p110α). These PIK3CA mutations occur as post-zygotic events and lead to a gain of function of PI3K, with consequent constitutional activation of the downstream cascades (e.g., AKT/mTOR pathway), involved in cellular proliferation, survival and growth, as well as in vascular development in the embryonic stage. PIK3CA-related cancers and PROS share almost the same PIK3CA mutational profile, with about 80% of mutations occurring at three hotspots, E542, E545, and H1047. These hotspot mutations show the most potent effect on enzymatic activation of PI3K and consequent downstream biological responses. If present at the germinal level, these gain-of-function mutations would be lethal to the embryo, therefore we only see them in the mosaic state. The common clinical denominator of PROS disorders is that they are sporadic conditions, presenting with congenital or early childhood onset overgrowth with a typical mosaic distribution. However, the severity of PROS is highly variable, ranging from localized and apparently isolate overgrowth to progressive and extensive lipomatous overgrowth associated with life-threatening vascular malformations, as seen in CLOVES syndrome. Traditional therapeutic approaches, such as sclerotherapy and surgical debulking, are often not curative in PROS patients, leading to a recrudescence of the overgrowth in the treated area. Specific attention has been recently paid to molecules that are used and studied in the oncogenic setting and that are targeted on specific alterations of the pathway PI3K/AKT/mTOR. In June 2018, Venot et al. showed the effect of Alpelisib (BYL719), a specific inhibitor for the p110α subunit of PI3K, in patients with PROS disorders who had severe or life-threatening complications and were not sensitive to any other treatment. In these cases, dramatic anatomical and functional improvements occurred in all patients across many types of affected organ. Molecular testing in PROS patients is a crucial step in providing the conclusive diagnosis and then the opportunity for tailored therapy. The somatic nature of this group of diseases makes challenging to reach a molecular diagnosis, requiring deep sequencing methods that have to be performed on DNA extracted from affected tissue. Moreover, even analyzing the DNA extracted from affected tissue there is no guarantee to succeed in detection of the casual somatic mutation, since the affected tissue itself is highly heterogeneous and biopsy approaches can be burdened by incorrect sampling or inadequate tissue sample. We present an 8-year-old girl with CLOVES syndrome, born with a large cystic lymphangioma involving the left hemithorax and flank, multiple lipomas, and hypertrophy of the left foot and leg. She developed severe scoliosis. Many therapeutic approaches have been attempted, including Sildenafil treatment, scleroembolization, laser therapy, and multiple debulking surgeries, but none of these were of benefit to our patient's clinical status. She then started treatment with Rapamycin from May 2019, without significant improvement in both vascular malformation and leg hypertrophy. A high-coverage Whole Exome Sequencing analysis performed on DNA extracted from a skin sample showed a mosaic gain-of-function variant in the PIK3CA gene (p.H1047R, 11% of variant allele frequency). Once molecular confirmation of our clinical suspicion was obtained, after a multidisciplinary evaluation, we decided to discontinue Sirolimus and start targeted therapy with Alpelisib (50 mg/day). We noticed a decrease in fibroadipose overgrowth at the dorsal level, an improvement in in posture and excellent tolerability. The treatment is still ongoing.