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.

[Off-label drugs in childhood psoriasis]. / Prescriptions hors AMM (autorisation de mise sur le marché) dans le psoriasis de l'enfant.

INTRODUCTION: Psoriasis affects 0.5% of children in Europe, with moderate to severe clinical forms in 15-35% of cases warranting the use of systemic treatments. Few treatments are licensed for childhood psoriasis. In this study, we analyzed the frequency of such prescriptions. MATERIALS AND METHODS: Our study was based on 3 retrospective cohort trials conducted in France between 2012 and 2018: χ-Psocar (313 children with psoriasis seen in hospitals), PsoLib (207 children seen in a private practice), and BiPe (134 children on biotherapies). Our evaluation was centered on off-label use. To avoid duplicates between cohorts, analysis focused on each cohort independently. RESULTS: In the χ-Psocar study, in 34.8% of cases, use of at least one off-label treatment, mainly topical vitamin D (36.0%), and systemic treatments (methotrexate and cyclosporine) was noted, on account of either the clinical type of psoriasis (13.7%) or patient age (24.6%). In the PsoLib study, in 41.5% of cases, at least one off-label treatment was noted, mainly combined calcipotriol-betamethasone (24.2%), ciclopirox shampoo (7.2%) and systemic treatments (n=20). The main reason was patient age (41.5%). In the BiPe study, in 97.0% of cases, at least one off-label treatment was noted. These prescriptions mainly concerned a combination of calcipotriol-betamethasone (68.7%) and tacrolimus (11.2%) along with systemic treatment comprising methotrexate, cyclosporin, methoxsalen or apremilast (n=125), but also biotherapies (n=85). The biotherapies were used off-label since at that time they had not yet been granted marketing authorisation. DISCUSSION: This study focused on 3 cohorts of children with psoriasis seen either in private practice or in a hospital setting, and it involved all types of treatment. Off-label prescriptions ranged from one-third to almost 100% of the children, depending on the individual cohorts. The prescribed drugs were topical treatments, conventional systemic drugs and biotherapies. Off-label prescription is not strictly prohibited in France provided it is within a well-defined regulatory framework. Where there is a rich bibliography, confident recommendations may be made. Unfortunately, in childhood psoriasis, the literature and recommendations are very limited, leaving prescribers with considerable individual responsibilities. Review of the license concerning children with psoriasis, a push to conduct therapeutic studies and the drafting of recommendations all appear necessary.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

[Ichthyosis prematurity syndrome: Two new cases]. / Le syndrome « ichtyose-prématurité ¼ : deux nouveaux cas.

BACKGROUND: Ichthyosis prematurity syndrome is a rare syndromic form of ichthyosis caused by mutations in FATP4, which plays a central role in the transport and activation of fatty acids in the epidermis and in epidermal barrier function. Despite stereotypical clinical presentation in the neonatal period, the diagnosis is not well known by clinicians. Herein we report two new cases. PATIENTS AND METHODS: Case no. 1: a boy born prematurely (33weeks of gestation) to non-consanguineous French parents presented at birth with respiratory distress necessitating admission to intensive care. His skin was covered by a thick caseous vernix, especially on the scalp, eyebrows and 4 limbs. At the age of 4years, the boy's skin appeared normal. Case no. 2: a boy born prematurely to consanguineous Moroccan parents (34weeks of gestation) presented at birth with respiratory distress requiring admission to intensive care. At clinical examination, he had a whitish thick skin giving an impression of vernix caseosa, with involvement of the scalp, forehead, 4 limbs and abdomen. At the age of 2 years, his skin was normal. CONCLUSION: The clinical presentation of this syndrome is typical. It is important to make the diagnosis to enable genetic counseling and planning of adequate neonatal care in the event of future pregnancies.

Reconstructed human epidermis for in vitro studies on atopic dermatitis: A review.

Atopic dermatitis (AD) is a chronic inflammatory skin disease causing a strong impact on quality of life. Its pathophysiology is the result of complex interactions involving immunological, genetic and environmental factors. Although there are several published in vitro three-dimensional models mimicking AD, none of them have taken all these pathophysiological features into account; thus, finding the right model may be complicated. This paper reviews the literature on the different reconstructed epidermis models of AD as well as their relevance. We focused our attention on both the defect of the epidermal barrier and the inflammation linked to the immune system.