French national protocol for the management of congenital ichthyosis.

Congenital ichthyoses (CI) comprise a heterogeneous group of monogenic genetic skin diseases characterized by diffuse scaling, often associated with skin inflammation. Diagnosis of the individual form of ichthyosis is complex and is guided by clinical expertise. CI usually has a major impact on quality of life (QOL) and thus requires lifelong treatment. To date, there are no curative therapies, although various symptomatic treatment options exist. The present protocol for the management of CI has been drawn up in accordance with the recommendations published in 2012 by the French National Authority for Health, based on a literature review, with the help and validation of members of the French network for rare skin diseases (FIMARAD). It provides a summary of evidence and expert-based recommendations and is intended to help clinicians with the management of these rare and often complex diseases.

Perception of Oral Health-Related Quality of Life in Children with Epidermolysis Bullosa: A Quantitative and Qualitative Study.

KNOWLEDGE TRANSFER STATEMENT: The results of this study confirm the difficulties experienced by patients in the oral sphere. They also show that patients are able to adapt and that their demands go beyond functional rehabilitation. This work should encourage dental practitioners to be part of the overall management of the disease, involving regular checkups, preventive dental measures, and oral hygiene education. Therefore, more effective communication is required, not only between the dental and dermatological teams but also with the parents and caregivers.

Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice.

BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.

Dermatologic manifestations in paediatric neurofibromatosis type 2: a cross sectional descriptive multicentric study.

BACKGROUND: Neurofibromatosis type 2 (NF2) is characterized by bilateral vestibular schwannoma (VS) more often in adults but a severe paediatric form with multiple neurological tumours is also described. In this population, a early diagnosis is important to prevent the onset of neurological complications but is difficult, particularly without a familial history. Cutaneous manifestations, which may precede VS or neurological tumours by several years, may contribute to an early diagnosis, but specific studies are lacking. The objective of this study was to characterize cutaneous manifestations of NF2 in a paediatric population. RESULTS: This observational, descriptive and multicentric study was conducted from April 2019 to April 2020 in seven academic French hospitals. We included patients ≤ 18 years old who fulfilled the Manchester diagnostic criteria or had a pathogenic mutation identified in the NF2 gene. All patients underwent a dermatological examination guided by a standardized questionnaire. 21 children were included, of whom 20 had at least one skin tumour (mean number 5 ± 4.6 [range 0-15]), which led to a diagnosis in four cases. In the other 17 cases, the diagnosis of NF2 was based on neurosensory complications (n = 10), family screening (n = 4) or ocular signs (n = 3). Before the NF2 diagnosis, 15 children had at least one "undiagnosed" cutaneous tumour that did not lead to a specific management. Patients' dermatological examination also revealed < 6 non specific café au lait macules (n = 15), hypopigmented macules (n = 12) with more than 3 lesions in 4 cases, and purple reticulated macules of the trunk (n = 4). CONCLUSION: Dermatological lesions are frequent and early in children with NF2 but rarely lead to the diagnosis. Cutaneous schwannomas are the most frequent but are often underdiagnosed. Café au lait macules are frequent, but atypical and mostly in small numbers. Multiple hypopigmented macules seem suggestive although inconsistent. The sensitivity of reticulated capillary malformation-like lesions remains to be assessed by further studies.

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.

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.

Gastrostomy for infants with severe epidermolysis bullosa simplex in neonatal intensive care.

INTRODUCTION: Severe epidermolysis bullosa simplex (EBS sev) is a rare genodermatosis characterized by congenital generalized blistering and mucosal involvement. Increased needs and decreased intake quickly lead to nutritional imbalance. Enteral nutrition support is proposed, but classical nasogastric tubes are not well tolerated in these patients and gastrostomy is preferred. OBJECTIVE AND METHODS: To report the experience with EBS sev in neonatal units of French reference centers for gastrostomy. In this retrospective multicentric study, we included all patients with EBS sev who had gastrostomy placement before age 9 months during neonatal care hospitalization. RESULTS: Nine infants (5 males/4 females) with severe skin and mucosal involvement were included. A gastrostomy was decided, at an early age (mean 3.7 months, range 1.4 to 8 months) in infants with mean weight 4426 g (range 3500 to 6000 g). Techniques used were endoscopy with the pull technique for 5 infants and surgery under general anesthesia for 4. Main complications were local but resolved after treatment. All infants gained weight after gastrostomy. The mean withdrawal time (n = 7) for the gastrostomy was 35.8 months (range 10.5 months to 6.5 years). Seven children had persistent oral disorders. CONCLUSIONS: Gastrostomy in infants with EBS sev can be necessary in neonatal intensive care units. Both surgical and endoscopic pull techniques seem efficient, with good tolerance.

Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters.

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.

Topical ropivacaine for analgesia of aplasia cutis congenita in newborns with hereditary epidermolysis bullosa.

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.

Genotypic and Phenotypic Analysis of 34 Cases of Inherited Junctional Epidermolysis Bullosa caused by COL17A1 Mutations.

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.

Incontinentia pigmenti in boys: Causes and consequences.

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.

Scabies polymerase chain reaction with standardized dry swab sampling: an easy tool for cluster diagnosis of human scabies.

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.

Ivermectin safety in infants and children under 15 kg treated for scabies: a multicentric observational study.

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.

Orofacial management for epidermolysis bullosa during wisdom tooth removal surgery: A technical note.

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.

[Staphylococcal toxic shock syndrome should be considered in the event of diffuse erythema with fever and shock]. / Érythème généralisé fébrile et choc : choc toxinique staphylococcique.

BACKGROUND: Toxic shock syndrome (TSS) was first described by Todd in 1978. The relevant Lancet publication reported 7 cases of children with fever, exanthema, hypotension and diarrhoea associated with multiple organ failure. An association between TSS and use of hyper-absorbent tampons in menstruating women was discovered in the 1980s. Following the market withdrawal of such tampons, TSS virtually disappeared. Herein we report a new case of TSS in a 15-year-old girl. PATIENTS AND METHODS: A 15-year-old patient was admitted to intensive care for severe sepsis and impaired consciousness associated with diffuse abdominal pain. Dermatological examination revealed diffuse macular exanthema. Laboratory tests showed hepatic cytolysis (ASAT 101 U/L, ALAT 167 U/L, total bilirubin 68µmol/L) and an inflammatory syndrome. Lumbar puncture and blood cultures were sterile while thoraco-abdomino-pelvic and brain scans were normal. The patient was menstruating and had been using a tampon over the previous 24hours. Vaginal sampling and tampon culture revealed TSST-1 toxin-producing S. aureus. Management consisted of intensive care measures and treatment with amoxicillin-clavulanic acid and clindamycin for 10 days. CONCLUSION: In case of septic shock associated with diffuse macular exanthema a diagnosis of TSS must be envisaged, particularly in menstruating women.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.