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The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.

Comment on [Attractiveness of a university hospital career in France: Analysis of perceptions among young dermatologists in 2016]. Soria A, Dreno B, Aractingi S, Beylot-Barry M, Bodemer C, Chosidow O, Cribier B, Lacour JP, Paul C, Richard MA, Gaudy-Marqueste C, Samimi M; les membres du Collège National des universités de dermato-vénéréologie, sous-section 50.03. Ann Dermatol Venereol. 2018 Mar;145(3):191-196. doi: 10.1016/j.annder.2017.11.003. Epub 2017 Dec 6.; National audience; Lettre à la rédaction

Lettre à la rédaction; National audience

International audience; Acute hemorrhagic edema of infancy is a rare but benign vasculitis occurring in infants aged from 4 to 24 months. Skin lesions can take various forms, including extensive hemorrhagic purpura, and can therefore be mistaken for purpura fulminans if associated with fever, which leads to initiating broad-spectrum antibiotic treatment. In the present case, we describe a 7-month-old boy with acute hemorrhagic edema of infancy and rapidly extensive purpura lesions that led to intravenous cefotaxime and amikacin treatment. Diagnosis was made on the next day by a dermatologist, based on the typical aspect of skin lesions, hemodynamic stability, and negative bacteriological samples. Coxsackie virus B5, a pathogenic enterovirus, was found by specific PCR in cerebrospinal fluid. The outcome was spontaneously favorable after discontinuation of antibiotics on day 2. We discuss the imputability of the enterovirus in triggering this case of acute hemorrhagic edema of infancy.; L’œdème aigu hémorragique du nourrisson (OAHN) est une vascularite rare et bénigne survenant chez des nourrissons de 4 à 24 mois. Les lésions cutanées, prenant parfois l’aspect d’un purpura ecchymotique ou en nappe, peuvent faire évoquer le diagnostic de purpura fulminans lorsqu’une fièvre y est associée et entraîner alors la mise en route d’une antibiothérapie. Nous rapportons le cas d’un nourrisson de 7 mois dont la présentation clinique initiale d’OAHN a fait suspecter un purpura fulminans. L’évolution rapide des lésions a fait instaurer une antibiothérapie par céfotaxime et amikacine. Le diagnostic d’OAHN a été porté le lendemain devant l’aspect des lésions cutanées, la stabilité hémodynamique de l’enfant et la négativité du bilan bactériologique. Un entérovirus (Coxsackie virus B5) a été mis en évidence secondairement par réaction de polymérisation en chaîne spécifique (PCR) dans le liquide céphalorachidien. Après arrêt de l’antibiothérapie, l’évolution a été spontanément favorable. L’imputabilité de l’entérovirus dans le déclenchement de cet OAHN est discutée.

International audience; BACKGROUNDThe prevalence of childhood psoriasis is estimated at between 0.4% and 0.7%. Clinical aspects of the diseases depend on age. The aim of this study was to investigate the clinical aspects of psoriasis according to age and sex.PATIENTS AND METHODSA cross-sectional, multicentre study of children with psoriasis was performed by investigators belonging to the Research Group of the French Society of Paediatric Dermatology. The study was conducted from April 2012 to March 2013. Inclusion criteria were age less than 18 years and clinical diagnosis of psoriasis. The children were classified into 3 groups by age: infants: 41%), but it accounted for only 25.9% of psoriasis of infants (P

International audience; Le terme de bébé collodion (BC) a été introduit en 1884 par Hallopeau pour décrire un nouveau-né présentant une membrane parcheminée recouvrant l’ensemble de son tégument [1]. Le phénotype BC est rare, estimé entre 1 pour 50 000 et 1 pour 100 000 naissances. Les séries de la littérature sont rares et rapportent de manière rétrospective au maximum une trentaine de cas. Il s’agit d’un état néonatal transitoire mais qui peut engager le pronostic vital à court terme en raison des complications. La mortalité est difficile à chiffrer précisément et a diminué au cours des années avec les avancées de la néonatologie. Les chiffres selon les publications varient entre 5 %, et 24 %. Le pronostic à long terme dépend de la maladie de la kératinisation sous-jacente, le plus souvent sévère, mais des issues favorables existent.

Incontinentia Pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of NF-kB signaling. In more than 80% of cases, IP is due to recurrent or non-recurrent deletions causing Loss-of-Function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion. We report here a new micro-indel (c.436_471delinsT, p.Val146X) arising through a DNA-replication-repair Fork-Stalling-and-Template-Switching (FoSTeS) and Microhomology-Mediated-End-Joining (MMEJ) mechanism in a sporadic IP case. The LoF mutations of IKBKG/NEMO leading to IP include small insertions/deletions (indel) causing frameshift and premature stop codons, which account for 10% of cases. We here present 21 point mutations previously unreported, which further extend the spectrum of pathologic variants: 14/21 predict LoF because of premature stop codon (6/14) or frameshift (8/14), while 7/21 predict a partial loss of NEMO/IKKgamma activity (2 splicing and 5 missense). We review how the analysis of IP-associated IKBKG/NEMO hypomorphic mutants has contributed to the understanding of the pathophysiological mechanism of IP-disease and has provided important information on affected NF-kB signaling. We built a locus-specific database listing all IKBKG/NEMO variants

International audience

We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.

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Richter's syndrome is a large-cell lymphoma occurring in patients with chronic lymphoid leukaemia (CLL). It is rarely limited to cutaneous locations. We report the case of a 61-year-old patient with CLL who developed multiple skin lesions due to immunoblastic lymphoma.Six years after onset of CLL controlled by chloraminophen, a tumoural syndrome developed and was treated by chemotherapy. A papulonecrotic cutaneous eruption was then observed on the face, the presternal area and then on the fingers. Skin biopsy revealed large-cell CD20+ CD30+ immunoblastic lymphoma. Polymerase chain reaction on the heavy chain immunoglobulins showed a band with the same size in the skin biopsy and in the circulating cells. No transformation was found in lymph node and bone marrow biopsies. The lesions disappeared after 4 treatments with VP16, cysplatin and methylprednisolone. CLL was again stabilized after the first chemotherapy sessions.Richter's syndrome is rarely discovered due to skin lesions. There have only been 4 similar cases reported in the literature. The clinical presentation of the lesions is insufficient to distinguish them from manifestations of CLL. Histological examination of the biopsy is required to make the diagnosis of high grade lymphoma. Prognosis is usually poor after discover of this type of lymphoma. This is the first observation of Richter's syndrome revealed by a skin lesion in which polymerase chain reaction suggested that the skin lymphoma and the CLL cells came from the same B clone.

The hypereosinophilic syndrome is an ill-defined nosological entity with predominant risks of cardiac and/or neurological lesions. In the light of new data on the effector cytotoxic effects of eosinophils, we have tried to establish new criteria of severity by purifying the circulating eosinophils of 14 patients with hypereosinophilic syndrome and testing their toxicity. This study has revealed the existence of low density ("hypodense") eosinophils with potential cytotoxicity in vitro. The worst clinical forms of the syndrome were observed in the group of patients with positive eosinophil toxicity tests. The significance of these cellular changes (hypodensity, eosinotoxicity) and their relationship with the clinical manifestations are discussed.

P63 is a major transcription factor regulating skin development and homeostasis. It controls many genes involved in cell proliferation, adhesion, and early differentiation. P63 is mutated in several rare syndromes called p63-related ectodermal dysplasia syndromes (ED). The main forms are EEC and AEC syndromes due to p63 missense mutations on the DBD and SAM domains, respectively. ED patients display many developmental defects, including ectrodactyly, clef/lip palate, and ectodermal dysplasia, while AEC patients suffer from severe skin erosions that not always heal. We have previously showed that ED-derived iPSC display altered epidermal commitment. P63 belongs to the p53 gene family sharing similar structural domains. We found that ED-iPSC epidermal commitment can be rescued by a p53-reactivating compounds called PRIMA-1MET, also named APR-246 and currently used in anticancer clinical trials. Here, we established primary epidermal culture from two AEC children (S.F. and Y.M.) suffering from persistent skin erosions at age of 9 and 15, respectively. These patients carry missense mutations on the SAM domain (I576T and I537T). We found that primary keratinocytes (KCs) isolated from these AEC patients underwent altered epidermal differentiation that was rescued by PRIMA-1MET treatment. It prompted us to formulate the compound onto a cream that was topically applied on the right hand of one patient and on the scalp of the second patient. In both cases, the daily treatment allowed re-epithelialization of the eroded skin and a drastic loss of pain after few weeks, improving quality of life. Normally, mutant p63 exerts a dominant-negative effect, mainly through the formation of aggregate with WT p63 and p73. PRIMA-1MET did not reduce protein aggregation while enhancing cell differentiation, suggesting that PRIMA-1MET targets cell differentiation and not p63 activity directly. In conclusion, we propose that repurposing of the antitumoral PRIMA-1MET compound could become a general treatment of AEC skin erosions.

Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling. In more than 80% of cases, IP is due to recurrent or nonrecurrent deletions causing loss-of-function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion. We report here a new microindel (c.436_471delinsT, p.Val146X) arising through a DNA-replication-repair fork-stalling-and-template-switching and microhomology-mediated-end-joining mechanism in a sporadic IP case. The LoF mutations of IKBKG/NEMO leading to IP include small insertions/deletions (indel) causing frameshift and premature stop codons, which account for 10% of cases. We here present 21 point mutations previously unreported, which further extend the spectrum of pathologic variants: 14/21 predict LoF because of premature stop codon (6/14) or frameshift (8/14), whereas 7/21 predict a partial loss of NEMO/IKKgamma activity (two splicing and five missense). We review how the analysis of IP-associated IKBKG/NEMO hypomorphic mutants has contributed to the understanding of the pathophysiological mechanism of IP disease and has provided important information on affected NF-kB signaling. We built a locus-specific database listing all IKBKG/NEMO variants, accessible at http://IKBKG.lovd.nl.