Search

International audience; ABSTRACT Purpose PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. Methods Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. Results Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort ( n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). Conclusion Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use. more...

ispartof: J Am Acad Dermatol vol:87 issue:4 pages:872-874 ispartof: location:United States status: published

Annular lipoatrophy of the ankle is a rare and unique acquired lipoatrophic panniculitis that mainly affects children. There is no consensus on treatment, and the long-term course is not well known. We present four new pediatric cases that contribute to the understanding of this rare disease. more...

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient. more...

Background The diagnosis of PTEN hamartoma tumor syndrome (PHTS) is difficult in children because they usually do not meet diagnostic criteria. The objective of our study was to characterize lipoma as an early presentation of PHTS. Methods We performed a retrospective review of children with PHTS diagnosed in French academic hospitals from 2000 to 2019. We included patients presenting at least one lipoma and PTEN-related disorder confirmed genetically. Results Thirteen children were included (mean age 5.5 years [range 2.5-16]). All children had solitary (n = 5) or multiple (n = 8) lipomas, all located on the trunk. Clinical examination revealed macrocephaly in all patients. Genital lentiginosis was found in all patients in whom genitalia were examined (n = 6). Conclusions In addition to the classical presentation of PHTS with neurological disorders and macrocephaly, some patients, especially the youngest ones, have an initial dermatologic presentation with multiple lipomas. Search for penile freckling and macrocephaly in these patients allows for the diagnosis of PHTS. Lipomatosis should be a major diagnostic criterion in children. more...

Integrated photonics will play a key role in quantum systems as they grow from few-qubit prototypes to tens of thousands of qubits. The underlying optical quantum technologies can only be realized through the integration of these components onto quantum photonic integrated circuits (QPICs) with accompanying electronics. In the last decade, remarkable advances in quantum photonic integration have enabled table-top experiments to be scaled down to prototype chips with improvements in efficiency, robustness, and key performance metrics. These advances have enabled integrated quantum photonic technologies combining up to 650 optical and electrical components onto a single chip that are capable of programmable quantum information processing, chip-to-chip networking, hybrid quantum system integration, and high-speed communications. In this roadmap article, we highlight the status, current and future challenges, and emerging technologies in several key research areas in integrated quantum photonics, including photonic platforms, quantum and classical light sources, quantum frequency conversion, integrated detectors, and applications in computing, communications, and sensing. With advances in materials, photonic design architectures, fabrication and integration processes, packaging, and testing and benchmarking, in the next decade we can expect a transition from single- and few-function prototypes to large-scale integration of multi-functional and reconfigurable devices that will have a transformative impact on quantum information science and engineering., JPhys Photonics, 4 (1), ISSN:2515-7647 more...

Summary Introduction Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by mutation of the NEMO/IKBKG gene. While lethal in male foetuses, heterozygous females survive because of X-inactivation mosaicism. Herein we discuss 9 male patients with IP. Materials and methods This is an observational, descriptive, retrospective, multicentre, French study carried out with the help of the SFDP research group. Statistical analysis was performed both on our own patients and on those reported in the literature. Results Nine boys with no family history of IP but with typical neonatal skin reactions were included. Genetic analysis of blood (n = 8) and skin biopsy (n = 3) confirmed the diagnosis of IP by identification of common deletion of the IKBKG/NEMO gene (exons 4 to 10) in the state of somatic mosaic in 6 and 2 cases respectively. Where analysed, the karyotype was normal (n = 6). Over a median follow-up period of 48 months (3 months to 10 years), 3 patients had neurological abnormalities, 2 had severe ophthalmologic abnormalities, and 1 had dental abnormalities. Extensive skin involvement is a systemic risk factor, unlike cutaneous scarring. Conclusion IP in boys is often due to a mosaic mutation that should be sought in blood and skin. Long-term neurological and ophthalmological monitoring is essential, especially in cases of extensive skin involvement. more...

Introduction Epidermolysis bullosa (EB) is a heterogeneous group of genetic diseases characterized by cutaneous and/or mucosal fragility. Blisters can occur spontaneously or because of minor friction on facial skin or the oral cavity. The repercussions of these dermatoses complicate the management of patients during surgery; for example, wisdom teeth removal might be complicated because of the limited mouth opening and mucosal lesions may be aggravated when the area of the wisdom teeth is being explored. Here, we describe the orofacial surgical management procedure for the extraction of the wisdom teeth of a patient with microstomia complicated by dystrophic epidermolysis bullosa (DEB) with high risk of mucosal lesion aggravation. Technique A 25-year-old woman with recessive DEB sought extraction of four wisdom teeth because of inclusion, recurrent pain, and dental caries. Anaesthesia was supported with conventional sequence induction and fibre-optic device-assisted nasotracheal intubation. A paediatric cuffed endotracheal tube and a fiberscope were lubricated before use in order to reduce friction against the naso-oropharyngeal mucosa. Hydrocellular foam dressing was applied on the face with soft adhesive silicone to avoid cutaneous wounds. No pressure was exerted on the patient's body during surgery. Surgical retractors were covered with hydrocellular foam dressing with silicone, and the labial commissures were protected with petroleum jelly. The dental extractions were performed with caution. Discussion Intraoral blistering in EB and scarring may result in microstomia and obliteration sulci, which can lead to difficulties in navigating the oral cavity. Consensus on a reasonable treatment protocol is lacking because no large cohort study exists. Lack of preparation of the facial skin and surgical instruments can lead to aggravation of lesions, especially when reaching for the third molars. A standardized procedure with general anaesthesia might pose fewer difficulties during the operation and limit facial and oral lesion aggravation. Prophylactic extraction of the third molar in younger patients with EB should be considered to avoid complications. Conclusion Atraumatic anaesthesia procedures and specific surgical care for these patients can be provided by using a protocol that protects the skin and mucous membranes from traumas. more...

International audience; BACKGROUND: Scabies is a frequent condition seen in infants and children. Only topical treatments have been approved in infants, but some of them are poorly tolerated. Oral ivermectin is approved for the treatment of scabies in several countries, but its use in infants and children weighing < 15 kg is off label. OBJECTIVES: To assess the safety of ivermectin in infants and young children, and to collect data on ivermectin efficacy in these age groups. METHODS: This study was performed in the dermatology and paediatric dermatology departments of 28 French centres between July 2012 and November 2015. Physicians treating an infant or child weighing < 15 kg for scabies with oral ivermectin were asked to send back a completed standardized and anonymous questionnaire, and the data were analysed. RESULTS: Data were collected on 170 infants and children aged 1-64 months, with a body weight of 4-14·5 kg, who were treated with oral ivermectin. The mean dose received was 223 μg kg-1 and 89% of the patients received a systematic second dose. Concomitant topical treatment was administered to 73% of patients. Adverse events were reported in seven patients (4%) and were not severe. At the follow-up visit, 139 (85%) patients had achieved healing. Factors significantly associated with healing were an ivermectin dose > 200 μg kg-1 (P < 0·001), and a delay between those two doses of < 10 days (P = 0·025). CONCLUSIONS: Our findings suggest the safety and efficacy of ivermectin for the treatment of scabies in infants and young children. What's already known about this topic? Scabies is a frequent condition in small children and infants, but the therapeutic options are limited. Ivermectin has been approved for the treatment of scabies in adults and children > 15 kg, but its use is off-label in infants and children weighing < 15 kg. Safety data on the use of ivermectin in children weighing < 15 kg are limited. What does this study add? Of 170 infants and children weighing < 15 kg who were treated for scabies with oral ivermectin, there were only seven reported mild adverse events and no serious ones. Our results show that ivermectin is effective in treating scabies in 85% of patients. Efficacy is higher when the received dose exceeds 200 μg kg-1 and when the delay between the two doses is < 10 days. Respond to this article. more...

We demonstrate scalable and intercompatible multilayer photonic platforms that operate over a multioctave wavelength range from the near-ultraviolet (NUV) into the short-wave infrared (SWIR). We demonstrate low-loss waveguides ( $\leq$ 3 dB/cm above 370 nm and more...

Species ranges are changing in response to human-related disturbances and often management and conservation decisions must be based on incomplete information. In this context, species distribution models (SDMs) represent the most widely used tool, but they often lack any reference to demographic performance of the population under study, spatial structure of the habitat patches, or connectivity at the landscape level. Combining a multi-state SDM with a landscape pattern analysis and a mortality model, we developed a spatially-explicit, integrated model to assist and inform conservation planning for the Apennine brown bear in central Italy. We identified 15 critical habitat areas, potentially hosting 76 adult female bears. Many of these areas are, however, characterized by high levels of human-related mortality, making them attractive sink-like areas. Structural connectivity was higher in the northern part of the study area while only limited connectivity characterizes the core area, where most of the bears currently live. Our integrated model indicates that the conservation of this relict and isolated bear population is a realistic conservation goal, as we estimated that 192–270 bears could live across the Apennines. Our modelling framework enhances the biological realism of traditional SDMs and provides a conservation planning tool that integrates habitat suitability, mortality risk (as a component of the total demographic performance) and structural connectivity among habitat patches at the landscape scale. It is particularly suited for endangered species living in a human-modified landscapes where establishing a realistic and spatially explicit conservation goal would facilitate pro-active management. more...

Resume Introduction Le toxic shock syndrome (TSS) a ete decrit pour la premiere fois par Todd en 1978. Cette publication du Lancet rapportait 7 cas d’enfants presentant une fievre, un exantheme, une hypotension et une diarrhee associes a une defaillance multiviscerale. C’est dans les annees 1980 qu’une association entre TSS et femmes en periode de menstruation utilisant des tampons hyperabsorbants a ete decouverte. Apres le retrait du marche de ce type de tampon, le TSS a quasiment disparu. Nous rapportons un nouveau cas de TSS survenu chez une adolescente. Observation Une jeune fille de 15 ans etait hospitalisee en reanimation pour un tableau brutal de choc septique avec troubles de la vigilance et douleurs abdominales diffuses. L’examen dermatologique trouvait un exantheme maculeux diffus. Le bilan biologique montrait une cytolyse hepatique (ASAT 101 U/L, ALAT 167 U/L, bilirubine totale 68 μmol/L) et un syndrome inflammatoire. La ponction lombaire et les hemocultures etaient steriles. La tomodensitometrie cerebrale et thoraco-abdomino-pelvienne etait normale. Dans un contexte de menstruation, la patiente avait utilise un tampon hygienique plus de 24 h. Le prelevement vaginal et la culture du tampon mettaient en evidence un S. aureus producteur de la toxine TSST-1. La prise en charge consistait en mesures de reanimation et traitement par une association amoxicilline-acide clavulanique et clindamycine pendant 10 jours. Conclusion Un tableau de choc septique associe a un exantheme maculeux diffus doit faire evoquer le diagnostic de TSS, surtout dans un contexte menstruel. more...

Importance Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. Objective To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. Design, setting and participants This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers. Statistical analysis was performed on an intent-to-treat basis from December 4, 2019, to November 10, 2020. Interventions Patients underwent an observational period, then switched to an interventional period when they received oral sirolimus (target serum levels, 4-12 ng/mL). The switch time was randomized from month 4 to month 8, and the whole study period lasted 12 months for each patient. Main outcomes and measures The primary outcome was change in the volume of vascular malformations detected on magnetic resonance imaging scan (with centralized interpretation) per unit of time (ie, between the interventional period and the observational period). Secondary outcomes included subjective end points: pain, bleeding, oozing, quality of life, and safety. Results Among the participants (35 girls [59.3%]; mean [SD] age, 11.6 [3.8] years), 22 (37.3%) had a pure venous malformation, 18 (30.5%) had a cystic lymphatic malformation, and 19 (32.2%) had a combined malformation, including syndromic forms. Variations in the volume of vascular malformations detected on magnetic resonance imaging scans associated with the duration period were not overall significantly different between the interventional period and the observational period (all vascular malformations: mean [SD] difference, -0.001 [0.007]; venous malformations: mean [SD] difference, 0.001 [0.004]; combined malformations: mean [SD] difference, 0.001 [0.009]). However, a significant decrease in volume was observed for children with pure lymphatic malformations (mean [SD] difference, -0.005 [0.005]). Overall, sirolimus had positive effects on pain, especially for combined malformations, and on bleeding, oozing, self-assessed efficacy, and quality of life. During sirolimus treatment, 56 patients experienced 231 adverse events (5 serious adverse events, none life-threatening). The most frequent adverse event was an oral ulcer (29 patients [49.2%]). Conclusions and relevance This observational-phase randomized clinical trial allows for clarifying the goals of patients and families when starting sirolimus therapy for children older than 6 years. Pure lymphatic malformations seem to be the best indication for sirolimus therapy because evidence of decreasing lymphatic malformation volume per unit of time, oozing, and bleeding and increasing quality of life was found. In combined malformations, sirolimus significantly reduced pain, oozing, and bleeding. Benefits seemed lower for pure venous malformations than for the 2 other subgroups, also based on symptoms. Trial registration ClinicalTrials.gov Identifier: NCT02509468; clinicaltrialsregister.eu Identifier: 2015-001096-43. more...

We report 20 newborns who developed, at a median age of 7 days, large abdominal patches of radially arranged purplish telangiectasia in a bilateral and symmetrical pattern in relation to the midline, creating a "butterfly wing" pattern. Clinical examination was normal in 13 newborns, six newborns had abdominal distention, and one newborn had poor weight gain due to inadequate breastfeeding. Most lesions spontaneously resolved within 3 months and did not reoccur for 19 newborns. Transient abdominal telangiectasia of the newborn (TATN) appears to be a distinctive entity that has not been previously described. more...

Background A marked increase in frequency of acute acral eruptions (AAE) was observed in children during the COVID-19 pandemic in the spring period. Objectives In this observational multicenter study, based on children with AAE, we aimed to assess the proportion of household members possibly infected by SARS-CoV-2. Methods We collected data from all children observed with AAE, prospectively from April 7, 2020 to June 22, 2020, and retrospectively since February 28, 2020. The primary outcome was the household infection rate, defined as the proportion of family clusters having at least one member with COVID-19 infection other than the child with AAE (“index child”). The definition of a case was based on characteristic clinical signs and a positive PCR or serology. Results The study included 103 children in 10 French departments and in Quebec. The median age was 13 years and the interquartile range [8–15], with a female-to-male ratio of 1/1.15. In children with AAE, all PCR tests were negative (n = 18), and serology was positive in 2/14 (14.3%) cases. We found no significant anomalies in the lab results. A total of 66 of the 103 families (64.1%) of included children had at least one other infected member apart from the index child. The total number of household members was 292, of whom 119 (40.8%) were considered possibly infected by SARS-CoV-2. No index children or households exhibited severe COVID-19. Discussion Among the 103 households included, 64.1% had at least one infected member. Neither children with AAE nor their households showed severe COVID-19. more...

Currently advanced MWIR camera systems’ shortcomings are related to 1) their high cost and being proprietary to large aerospace companies, 2) their compromise on power or frame rate, and 3) their compromise on noise and well capacity as the pixel pitch goes down and the array size is increased. This paper presents a novel low SWAP-C commercially available high-end MWIR camera system development. The camera incorporates a 10-micron pitch MWIR FPA with a 3- megapixel array size read out at full motion video rate, and even up to 90Hz rate. The small pitch sensor has various gain modes up to 20 million-electron well capacity as well as low noise at high readout rates delivering full 14-bit performance. more...

An 8-inch wafer scale process was developed that provides low cost availability of back-side illuminated (BSI) imaging sensors. The process has been optimized to convert standard CMOS and CCD 6-inch or 8-inch wafers from front side illuminated (FSI) sensors to BSI sensors. The process successfully demonstrates wafer planarization, bow correction, bonding to carrier wafers, wafer thinning, re-planarization, anti-reflection coating, through silicon vias (TSVs) and back side metallization. Good wafer thinning control was obtained for a wide range of epi thicknesses varying from 4 microns to 15 microns. The thinner epi is optimized for UV and visible sensing while the thicker epi material is optimized for near-infrared (NIR) sensing. The processed wafers demonstrate backside passivation and anti-reflection (AR) coatings that optimize the QE performance in a variety of bands such as 200nm-300nm, 300nm-400nm and 400nm-900nm. more...

International audience

Importance Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. Objective To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic. Design, setting, and participants In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included. Main outcomes and measures Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. Results Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. Conclusions and relevance Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy. Trial registration ClinicalTrials.gov Identifier: NCT04344119. more...

Integrated photonic technologies for quantum applications are discussed with emphasis on those supporting trapped-ion-based systems. A long-term vision of a fully integrated trapped- ion chip and current work towards its realization are presented. more...

Background Health care transition (i.e., transition from pediatric to adult care) is challenging in chronic conditions but has been poorly studied in rare chronic skin diseases. We investigated the proportion of lost to follow-up among patients with superficial vascular malformations after health care transition. We also collected patients’ opinions. This prospective, multicenter, cross-sectional study was performed at 7 French hospitals. We included patients aged 19–25 years, who were followed for a superficial vascular malformation before age 16, and who had completed the transition period in 2020. Data were collected from medical records and a questionnaire was sent to included patients asking about the health care transition. Results Among the 90 patients included, 41 (46%) were lost to follow-up after health care transition period. The age at diagnosis was significantly higher for lost to follow-up than non- lost to follow-up patients. The lost to follow-up proportion was similar between patients who changed and did not change hospitals during the transition. Responses to the questionnaire were obtained for 47 of 90 patients (52.2% response rate); most were satisfied with their care (n = 31/36, 86.1%); however, a lack of psychological support was reported. Conclusions Health care transition is associated to a high rate of lost to follow-up. Early management seems associated to less lost to follow-up. Further studies are needed to better understand risk factors for a failed health care transition and its consequences. more...

Recently, several case series of cutaneous acral manifestations in patients with suspected or confirmed coronavirus disease 2019 (COVID‐19) have been reported. A majority of these acral manifestations have a pseudo‐chilblain pattern with erythema and oedema and sometimes vesicles. more...

Aplasia cutis congenita (ACC) in patients with hereditary epidermolysis bullosa (EB) is often associated with major pain. We report our experience with using topical ropivacaine during dressing in newborns with ACC. Eight full-term newborns with EB and ACC were hospitalized in a neonatal intensive care unit for severe pain during dressing despite the use of paracetamol, opioids (n = 8) or ketamine (n = 7). Topical xylocaine was poorly tolerated and not effective. Ropivacaine 2 mg/ml was used directly in contact with the ACC, with a maximum 1 mg/kg/day, which enabled care without the child crying. No immediate or late systemic toxicity was observed. Topical ropivacaine 0.2% appears to be an interesting topical analgesic, with good clinical tolerance and rapid action, in newborns with ACC and EB. These data need to be confirmed in a prospective study including pharmacokinetics evaluations. more...

Inherited epidermolysis bullosa defines a heterogeneous group of genodermatoses characterized by skin and/or mucosa fragility resulting in blistering. The junctional variant (JEB) is associated with mutations affecting the genes expressing the components of the dermo-epidermal junction (DEJ) [1-2]. We report 34 JEB patients with COL17A1 genetic mutations diagnosed in our Center between 1993 and 2019. Medical and biological records were collected with a standardized questionnaire. more...

International audience; No abstract available

Resume Introduction Le « syndrome ichtyose-prematurite » est tres rare ; il appartient au groupe des ichtyoses syndromiques. Il est du a des mutations du gene FATP4, lequel joue un role cle dans le transport et l’activation des acides gras de l’epiderme et dans la fonction barriere cutanee. Malgre une presentation clinique stereotypee en periode neonatale, l’affection est peu connue des cliniciens. Nous en rapportons deux nouveaux cas. Observations Cas no 1 : il s’agissait d’un enfant de sexe masculin, d’origine francaise, ne de parents non apparentes a 33 semaines de gestation. A la naissance, l’enfant presentait une detresse respiratoire prise en charge en reanimation neonatale. Sur le plan cutane, on notait un aspect de vernix caseosa epais atteignant principalement le cuir chevelu, les sourcils et les quatre membres. L’evolution etait favorable, avec un examen cutane normal a 4 ans. Cas no 2 : il s’agissait d’un enfant de sexe masculin, d’origine marocaine, ne de parents apparentes a 34 semaines de gestation. A la naissance, il presentait une detresse respiratoire aigue prise en charge en reanimation neonatale. A l’examen clinique, il avait un aspect epaissi de la peau mimant un vernix caseosa, blanchâtre, localise principalement sur le cuir chevelu, le front, les quatre membres et l’abdomen. L’evolution etait favorable, avec un examen cutane normal a 2 ans. Conclusion Nos deux patients illustrent la presentation clinique caracteristique de ce syndrome, qui merite d’etre connu des cliniciens pediatres et dermatologues afin de poser le diagnostic, de realiser un conseil genetique et de prevoir une prise en charge adaptee de la periode perinatale en cas de future grossesse. more...

Resume Introduction La keratodermie aquagenique (KA) est caracterisee par l’apparition de papules blanchâtres, d’un aspect fripe et d’une desquamation des mains au contact avec l’eau. En dehors du contexte de la mucoviscidose, la KA semble rare (13 cas) et mal connue chez l’enfant. De plus, l’association a la mucoviscidose est source de peurs chez les parents et les medecins. L’objectif de ce travail est de decrire les caracteristiques et de discuter la prise en charge de la KA de l’enfant. Materiel et methode Etude retrospective, multicentrique, incluant les enfants de moins de 16 ans atteints de KA. Resultats Chez les 12 enfants inclus, l’âge median de debut etait de 9,25 ans (20 mois–15 ans). L’aspect clinique et le mode de survenue etaient classiques ; l’atteinte des paumes etait plus severe que celle des plantes. Des signes fonctionnels etaient associes dans six cas. Le retentissement median etait de 1,5 sur une echelle de 10. Le test de la sueur etait negatif chez deux patients. L’analyse moleculaire du gene CFTR, realisee chez trois patients, etait negative chez un et montrait une mutation heterozygote dans les deux autres cas. L’evolution se faisait vers la stabilite chez huit patients, l’aggravation chez deux autres, la guerison et l’amelioration chacune dans un cas. Discussion C’est a notre connaissance la premiere serie de KA de l’enfant. Les caracteristiques cliniques ne different pas significativement de celles de l’adulte ; le retentissement est modere et l’evolution variable. Un bilan systematique visant a eliminer une mucoviscidose ne semble pas justifie chez l’enfant puisque a ce jour aucune mucoviscidose n’a ete diagnostiquee devant une KA isolee. Conclusion La KA est rare chez l’enfant ; elle ne doit pas inquieter a tort et peut evoluer vers l’amelioration ou la guerison. more...

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal adverse reaction. It can be difficult to diagnose, even more so among children, because symptoms may mimic other commonly encountered pediatric conditions. Objective To describe clinical and laboratory features of DRESS syndrome in the pediatric population (age ≤18 years) and establish causative agents and treatment modalities. Methods This was a multicenter retrospective study of probable and definite DRESS cases (Registry of Sever Cutaneous Adverse Reaction score ≥ 4) in children hospitalized in 15 French university hospitals between 2000 and 2020. Results We included 49 cases. All children had fever and rash, 69.4% had lymphadenopathy, and 65.3% had facial edema. The most common organ affected was the liver (83.7%). Treatment consisted of topical corticosteroid in only 30.6% and systemic corticosteroid in 55.1%; 12.2% received intravenous immunoglobulin. Among probable and likely culprit drugs, 65% were antibiotics and 27.5% were antiepileptics, median time to DRESS symptom onset after initiation of 15 days (13 days with antibiotics and 21 days with antiepileptics). Twenty-seven children had allergy assessment for causative agents, 65.4% of whom had positive tests. Conclusions Culprit drugs are frequently antibiotics and antiepileptic drugs, and onset is often less than 2 weeks after treatment starts, especially with antibiotics. Treatment with topical corticosteroids appears to be sufficient in the least severe cases. Treatment by systemic corticosteroid therapy remains the reference treatment in case of severe organ damage. more...

Psoriasis affects 2–4% of the population, with the most common clinical type being plaque psoriasis. The linear form of psoriasis is very rare. The literature on linear psoriasis (LP) consists of only case reports, and data are few. This study aimed to better understand LP in a large-scale study. We retrospectively retrieved the medical records from 14 French medical centers of patients newly diagnosed clinically with LP, with or without the support of histology, between 1 February and 31 July 2015. For each case, we assessed the clinical features, treatments and treatment efficacy. In total, 30 cases of LP (mean age 26.8 years, 13 males) were reported. Mean age at onset of LP was 20.0 years, with 18 developing LP in childhood. Ten patients had a family history of psoriasis, and two had psoriatic arthritis. A total of 19 cases were linear at onset, with concomitant classical psoriasis; these were termed “superimposed” LP. The remaining 11 cases were not associated with classical psoriasis and were termed “isolated” LP. In four of the superimposed cases, LP developed when the patient was receiving systemic treatment: methotrexate (n = 2), etanercept (n = 1) or infliximab (n = 1). Topical steroids were effective in 76% of cases in which they were used, and systemic treatment was effective in more...

SummaryBackground Genetics discoveries have allowed for better understanding capillary malformations (CMs) with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. Objective We aimed to identify clinical and hemodynamic factors associated with leg length discrepancy (LLD) in children with CM of lower limbs. Methods Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inferieur), including children from 2 to 12 years old with CM of lower limbs. Clinical characteristics were prospectively collected. Hemodynamic factors were measured by an echographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. Results We analyzed data at baseline for 96 children. The mean (SD) age was 5.6 (3.1) years; 49 (51%) were male; and 14 (15%) showed LLD. Thirty-two patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies, and in 1 child, diagnosis of Parkes Weber syndrome was made. Only increased circumference above the knee was more frequent with than without LLD (50% vs 13%, p=0.02). In all, 10/79 patients (13%) showed a difference in ABF ≥50%: 4 had LLD. The frequency of differences in ABF ≥50% was greater with than without LLD [33.3% (n=4/12) vs 9.0% (n=6/67), p=0.04]. Conclusions ABF measured by Duplex ultrasonography is a simple, low-cost and non-invasive complementary examination for help in detecting LLD, with a difference ≥ 50% possibly associated. This article is protected by copyright. All rights reserved. more...

Resume Introduction Le rhumatisme psoriasique touche 20 a 30 % des patients atteints de psoriasis cutane. Peu de donnees epidemiologiques sont disponibles en France sur sa prevalence, ses associations avec l’atteinte dermatologique et ses comorbidites. Objectifs Evaluer les aspects epidemiologiques et associations cliniques et epidemiologiques du rhumatisme psoriasique chez les enfants et les adultes, en France. Methodes Deux etudes transversales, multicentriques ont ete menees en France chez les enfants (χ-Psocar, 23 centres de dermatologie pediatrique membres du GR SFDP, 1 an) et les adultes (Resopsocar, 29 centres de dermatologie membres du GEM RESOPSO, 4 mois) pour etudier les comorbidites cardiovasculaires et metaboliques du psoriasis. Resultats Parmi les 313 enfants (garcons : 47,6 % ; âge moyen, 9,4 ans) et 1954 adultes (hommes : 56,0 % ; âge moyen : 48,5 ans) atteints de psoriasis, 4,2 % des enfants et 21,0 % des adultes souffraient de rhumatisme psoriasique. La prevalence augmentait avec l’âge : 2,2 % des enfants, 14,2 % des adolescents et plus de 20 % apres 40 ans. Elle diminuait apres 70 ans (19,4 %). Quel que soit l’âge, le sexe n’etait pas associe au rhumatisme psoriasique. Chez les enfants, le rhumatisme etait associe a l’atteinte ungueale (p = 0,04) et a la severite de la maladie (p = 0,0004). Chez les adultes il etait associe au psoriasis en plaques (p = 0,002), a la severite de la maladie (p Conclusions Ces deux etudes transversales menees en France sur 2267 patients, principalement hospitaliers, donnent une idee de la prevalence du rhumatisme psoriasique tout au long de la vie. La prevalence augmente progressivement avec l’âge, sans difference de genre, avant de diminuer chez les personnes âgees. Nous confirmons l’association avec l’onychopathie psoriasique des l’enfance et avec l’obesite chez les adultes. more...

International audience; The paper presents an adaptive trajectory tracking control strategy for quadrotor Micro Aerial Vehicles (MAVs). The proposed approach, while maintaining the common assumption of an orientation dynamics faster than the translational one, removes the assumption of absence of external disturbances and of Geometric Center coincident with the Center of Mass. In particular, the trajectory tracking control law is made adaptive with respect to the presence of external forces and moments (e.g., due to wind) and to the uncertainty of parameters of the dynamic model, such as the position of the center of mass. A stability analysis is presented to analytically support the proposed controller, while numerical simulations are provided in order to validate its performance. more...

The year 2017 in pediatric dermatology was marked by several consensus recommendations and meta analyzes on childhood psoriasis, atopic dermatitis or PHACE syndrome, case series on the role of anti-JAK treatment in adolescent with alopecia areata, sirolimus for vascular malformations, ivermectine for rosacea, inhibitors of MEK for type 1 neurofibromatosis or on the side effects of the oral isotretinoin for acne or propranolol for immature hemangioma. Only few randomized controlled studies have been published on the interest of adalimumab in the treatment of psoriasis or topical sirolimus for angiofibroma in tuberous sclerosis complex for example. There were also clinical articles on various affections such as the sign of the scalp hair collar sign, childhood prurigo, ichthyosis, atopic dermatitis, warts or Zika virus infection. Finally, numerous publications reported new genes responsible for dermatosis in mosaics with new questionings and perspectives. more...

Monolithic integration of control technologies for atomic systems is a promising route to the development of quantum computers and portable quantum sensors. Trapped atomic ions form the basis of high-fidelity quantum information processors and high-accuracy optical clocks. However, current implementations rely on free-space optics for ion control, which limits their portability and scalability. Here we demonstrate a surface-electrode ion-trap chip using integrated waveguides and grating couplers, which delivers all the wavelengths of light required for ionization, cooling, coherent operations, and quantum-state preparation and detection of Sr+ qubits. Laser light from violet to infrared is coupled onto the chip via an optical-fiber array, creating an inherently stable optical path, which we use to demonstrate qubit coherence that is resilient to platform vibrations. This demonstration of CMOS-compatible integrated-photonic surface-trap fabrication, robust packaging, and enhanced qubit coherence is a key advance in the development of portable trapped-ion quantum sensors and clocks, providing a way toward the complete, individual control of larger numbers of ions in quantum information processing systems., Updated to be consistent with published version more...

Over the last decade, optical atomic clocks have surpassed their microwave counterparts and now offer the ability to measure time with an increase in precision of two orders of magnitude or more. This performance increase is compelling not only for enabling new science, such as geodetic measurements of the earth, searches for dark matter, and investigations into possible long-term variations of fundamental physics constants but also for revolutionizing existing technology, such as the global positioning system (GPS). A significant remaining challenge is to transition these optical clocks to non-laboratory environments, which requires the ruggedization and miniaturization of the atomic reference and clock laser along with their supporting lasers and electronics. Here, using a compact stimulated Brillouin scattering (SBS) laser to interrogate a $^8$$^8$Sr$^+$ ion, we demonstrate a promising component of a portable optical atomic clock architecture. In order to bring the stability of the SBS laser to a level suitable for clock operation, we utilize a self-referencing technique to compensate for temperature drift of the laser to within $170$ nK. Our SBS optical clock achieves a short-term stability of $3.9 \times 10^{-14}$ at $1$ s---an order of magnitude improvement over state-of-the-art microwave clocks. Based on this technology, a future GPS employing portable SBS clocks offers the potential for distance measurements with a 100-fold increase in resolution. more...

BACKGROUND: The spectrum of manifestations associated with Covid-19 infection is expanding continuously Increasing cases of cutaneous lesions are reported and

Background Expert visualization of Sarcoptes scabiei remains essential for diagnosing human scabies, but access to said experts can be difficult. Polymerase chain reaction (PCR) is a specific tool for the detection and confirmation of S. scabiei but has poor sensitivity. Objectives To evaluate PCR as a diagnostic method for scabies using nonexpert-dependent standardized sampling. Methods The dry swab was systematically rubbed across the front of both wrists, the eight interdigital spaces and on any suspected scabies lesions in all patients referred for scabies. A new PCR-based diagnostic test was run on the samples. All patients underwent clinical and dermoscopic examination. Scabies diagnosis was confirmed when dermoscopic examination was positive or the patient had typical clinical signs of scabies. Results Of 183 suspected cases of scabies, 164 patients were sampled, 87 had confirmed scabies (dermoscopy positive n = 87, typical clinical signs n = 1) and 77 did not. Of the 87 patients with proved scabies, 33 patients had positive scabies PCR, resulting in a 37·9% [95% confidence interval (CI) 28·4-48·4%] sensitivity and a 61·7% (95% CI 52·4-72·7%) negative predictive value. None of the 77 patients ruled out for scabies had a positive PCR result. Conclusions This method is nontraumatic, repeatable and non-expert-dependent. It shows sensitivity similar to previous studies involving expert skin scraping. However, this method facilitates the multiplication of sampling, which increased the sensitivity for cluster scabies diagnosis. This method may be suitable as a first-line diagnosis tool where a large cluster scabies outbreak is suspected. What's already known about this topic? Scabies diagnosis requires expertise. Scabies polymerase chain reaction (PCR) is specific but has poor sensitivity. Poor sensitivity is the consequence of the low efficiency of sampling methods. What does this study add? This PCR-based diagnostic method based on nontraumatic standardized skin sampling is not expert-dependent and is reproducible. This diagnostic method may be relevant as a non-expert sentinel diagnosis tool in large clusters where a scabies outbreak is suspected. more...

Introduction Le DRESS est une toxidermie severe rare et potentiellement fatale. La variabilite des presentations cliniques peut etre source d’errance diagnostique et de retard a la prise en charge. Le but de notre etude etait de decrire les caracteristiques du DRESS en population pediatrique. Materiel et methodes Etude retrospective multicentrique des cas de DRESS (Regiscar ≥ 3) chez des enfants ≤ 18 ans hospitalises entre 2000 et 2020. Resultats Nous avons inclus 53 cas, issus de 15 hopitaux francais. L’âge moyen etait de 8,6 ans avec une predominante feminine (54,7 %). Le DRESS survenait au cours d’une hospitalisation chez 11 enfants (20,8 %). Parmi les 90 molecules imputables, 57,8 % etaient des antibiotiques (AB), 21 % des antiepileptiques (AE). Le delai median d’apparition apres l’introduction etait de 13 jours (AB : 12, AE : 17). On notait un retard diagnostique median de 5 jours (jusqu’a 28). Un exantheme morbiliforme etait decrit dans 58,4 % des cas, une erythrodermie dans 26,4 %. La duree mediane de l’eruption etait de 20 jours (jusqu’a 90). Une fievre etait observee chez tous les enfants, un œdeme du visage chez 64,2 % et des adenopathies chez 67,9 %. Les organes touches etaient le foie (79,2 %), le rein (22,6 %), le poumon (20,8 %), la rate (13,2 %) et le systeme digestif (11,3 %). 83 % des enfants presentaient une hypereosinophilie > 500/mm3 (60,4 % > 1500/mm3). 17 (44,1 %) sur les 38 testes avaient une reactivation virale (PCR positive) : 7 HHV-6, 2 HHV-7, 4 Parvovirus B19, 2 EBV et 2 co-reactivations EBV-CMV. Pour le traitement du DRESS, 52,8 % des enfants ont eu une corticotherapie locale (duree mediane 8), 54,7 % une corticotherapie systemique (duree mediane 36,5 [min–max : 1 jour–11 mois]), 11,3 % des immunoglobulines intraveineuses et 3,8 % de la ciclosporine. La duree d’hospitalisation mediane etait de 11 jours. Des sequelles a long terme etaient observees chez 3 patients (5,7 %) : 1 HTA cortico-induite, 1 insuffisance corticotrope et 1 hyperpigmentation. Un enfant est decede d’un arret cardiorespiratoire sur myocardite. Vingt-cinq enfants (47,1 %) ont eu un bilan allergologique : 20 patch tests, 10 IDR, 3 pricks, 1 test de transformation lymphocytaire et 1 test de reintroduction. Quinze (60 %) avaient des tests positifs, 2 avaient une allergie a 2 molecules. Discussion Notre etude est la plus grande serie de DRESS pediatrique rapportee. Nos resultats sont concordants avec les cas publies (revues systematiques et cohortes retrospectives) et permettent de mieux preciser les caracteristiques clinicobiologiques du DRESS chez l’enfant. Les medicaments imputables sont frequemment des AB avec delai de survenue assez court ( Conclusion Le DRESS est mal connu des pediatres. Ce diagnostic doit etre systematiquement evoque chez l’enfant devant un exantheme cutane febrile des lors qu’un nouveau traitement a ete introduit dans les 12 dernieres semaines. more...

This study describes a numerical simulation of a miniature vortex combustion cold-wall chamber using a two-stage choked nozzle approach. Recognizing that the nozzle is choked at the throat under normal operation, the miniaturized vortex chamber is decomposed into two parts: The first segment extends from the headwall to the throat, whereas the second extends from the throat to the nozzle exit plane. In stage 1, an incompressible model is used leading up to the nozzle entrance. In stage 2, compressibility is superimposed, starting with the output from stage 1. This two-stage simulation reduces CPU time and helps to achieve convergence. Compressible simulations are then performed using a three-dimensional pressure-based, finite volume, unstructured solver. Furthermore, reaction mechanisms are simulated using a non-premixed combustion model with adiabatic probability density function lookup tables. Eight conventional chemical species are used, including O2, H2, H2O, HO2, H2O2, O, H, and OH. At the outset, th... more...

Hereditary epidermolysis bullosa (EB) is a heterogeneous group of rare genetic diseases characterized by fragile skin and/or mucous membrane, and it may be either local or generalized. It is caused by mutations in genes encoding different proteins involved mainly in the structure and function of the dermal-epidermal junction. Nineteen genes have so far been identified. They are classified by level of skin cleavage (from top to bottom) into four groups: EB simplex, junctional EB, dystrophic EB and Kindler syndrome. Clinically suspected diagnosis is confirmed by immunohistochemical examination of a skin biopsy at specialized centres in order to determine the level of cleavage and the deficient protein. This first step may be followed by genetic analysis. The severity of the disease is highly variable, ranging from localized forms with little effect on quality of life to rapidly lethal forms. In generalized severe forms, the extent and chronicity of lesions, as well as mucosal involvement, can lead to systemic complications: malnutrition, pain, joint contractures, chronic inflammation, amyloidosis, cutaneous squamous cell carcinoma. Some specific forms are associated with other cutaneous signs (nail involvement, alopecia, hyperpigmentation, palmoplantar keratoderma) or extracutaneous involvement (muscular dystrophy or pyloric atresia). No curative treatment of EB is available today. EB requires multidisciplinary medical care, nursing, psychological and social management. This is best provided by a specialized network, involving reference centres, centres of expertise and daily caregivers. The goal of treatment is the prevention and treatment of lesions with specific non-adherent dressings and the prevention, detection and treatment of complications. It is essential not to traumatize the skin (bandaging, friction, etc.). Protein, gene or cell replacement therapy, and allogeneic bone marrow, cord blood or pluripotent stem-cell transplantation are currently being assessed. The aim of these French recommendations (national diagnostic and treatment protocol [PNDS]) is to provide healthcare professionals with guidance on the course of EB and on optimal patient management. more...

Epidermolysis bullosa simplex is a group of inherited disorders with allelic and locus heterogeneity in which skin fragility and blistering within the skin occur. Mutations in KRT5 and KRT14 underlie the majority of reported cases. Mutations in KLHL24, a gene that encodes KLHL24 protein, have been reported recently to cause a generalized subtype of epidermolysis bullosa simplex, presumably by increasing the degradation of keratin 14. We describe a case of KLHL24-related epidermolysis bullosa simplex and highlight the burn-like pattern of scars. more...