C. Chiaverini

Prevalence of inherited ichthyosis in France: a study using capture-recapture method

BackgroundInherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.MethodsCapture – recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period.ResultsThe prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 – 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 – 2.6]).ConclusionsOur results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies.

Psoriasis and obesity in French children: a case–control, multicentre study

Obesity is more common in adults with psoriasis than in the general population, but there is a lack of data available regarding this association in children.

Systemic treatments in childhood psoriasis: a French multicentre study on 154 children

DEAR EDITOR, Psoriasis is a common, chronic, systemic inflammatory disease mediated by T lymphocytes. The main clinical presentation is plaque psoriasis. The incidence of psoriasis in the childhood population is estimated at 40 8 per 100 000, and the median age of onset among children is 7–10 years. In Europe psoriasis affects 0 5–1% of children. The physical, psychological and social impact of psoriasis and the association with comorbidity highlight the need for early management. The systemic treatments used for paediatric psoriasis are methotrexate, ciclosporin, acitretin, fumaric acid and biologics. In France, acitretin, ciclosporin and etanercept are licensed in children; methotrexate is licensed for patients aged > 18 years; and fumaric acid is not available. Furthermore, phototherapy cannot be used in children aged < 10 years. On the other hand, methotrexate is considered as the first-line therapy for severe psoriasis in childhood in most European countries. There are few data about the tolerance and efficacy of these treatments, and adult guidelines cannot be directly applied to children. We performed a retrospective study from June 2013 to June 2014 (collecting data from April 2000 to July 2014) in 19 French centres to evaluate the efficacy and tolerance of systemic treatments in children with psoriasis. Phototherapy alone was not included in this study. Patients included were aged < 18 years at the end of the evaluation and had moderate-to-severe psoriasis needing systemic treatment. The diagnosis of psoriasis was made clinically by a dermatologist expert in paediatric dermatology and/or psoriasis. The demographic, epidemiological and medical data were collected by a standardized questionnaire form. Psoriasis was considered as severe with Psoriasis Area and Severity Index (PASI) > 10, Physician’s Global Assessment (PGA) > 3, involved body surface area > 10% or inefficacy of topical treatments. For each treatment, the duration, maximum dose used, association of topical treatment, efficacy at 3 months (12 weeks), side-effects and reason for ending were specified. The efficacy was clinically evaluated by a dermatologist after 3 months of treatment. Efficacy was retrospectively classified as good response (clearance of > 75% of lesions), partial response (clearance of 50–75%), moderate response (clearance of 25–50%) or no response (clearance < 25%). Data were collected into a computerized database using Microsoft Excel software. Quantitative data were expressed as means and ranges, and qualitative data as n (%). We included 154 children (sex ratio 1 0, mean age 13 8 years) (Table 1). The mean age of onset of psoriasis was 7 7 years (range 0 2–17). The main type of psoriasis was plaque (55 8%). A family history of psoriasis was found in 49 4% of the children. Before the introduction of systemic treatment, the retrospective PGA for each treatment was 4 in almost half of the patients (49 8%) (Table 1). In total, 261 treatments were used among the 154 children. The mean age of onset of systemic treatment was 10 3 years (range 1–17), with a mean duration of treatment of 11 7 years (range 3–72). The mean delay between onset of psoriasis and treatment was 2 6 years (range 0– 14). Most of the patients required one course of treatment (55 2%). Acitretin was the most frequently used treatment (54 4%) and was used mainly as first-line treatment (76 6%). Topical treatments were associated with systemic treatments in 73 9% of the cases. The efficacy was good or partial across all systemic agents for 59 0% of treatments. The best efficacy was for phototherapy plus acitretin (80 0%). Overall, the efficacy tended to be similar across all systemic treatments. Absence of response was seen in approximately 10% of cases across all treatments (Table 1). The main reasons for stopping the treatment were clearance of disease (26 1% of cases) and inefficacy (26 8%) (Table 1). The efficacy rate was best for acitretin in plaque and pustular psoriasis; for methotrexate in plaque and guttate psoriasis; for ciclosporin in guttate psoriasis; and for biotherapy in the palmoplantar and erythrodermic forms (Table 2). Side-effects were noticed in 88 treatments (33 7%) among 55 children. Most of those side-effects were benign and had no influence on the duration of treatment (for 66 uses). Only 15 side-effects induced stopping of the treatment. Ciclosporin was the treatment with the highest rate of severe side-effects requiring termination of treatment (20%). According to this large descriptive study, acitretin and methotrexate may be considered as first-line therapy; ciclosporin can be used as first-line therapy but the side-effects are more frequent. Side-effects were frequent but mostly

Oral erythromycin therapy in epidermolysis bullosa simplex generalized severe.

DEAR EDITOR, Hereditary epidermolysis bullosa simplex generalized severe (EBS-gen-sev; formerly known as Dowling–Meara EBS) is the most severe form of EBS, and at present, no effective therapy exists. The use of tetracycline to treat EBS is controversial, and is contraindicated in childhood, when the disease can be most severe. Macrolides are used to treat various inflammatory skin diseases and are suitable for treating children. In this open-label preliminary study without controls, we evaluated whether oral erythromycin could be an effective and well-tolerated treatment in children with EBSgen-sev. Patients of both sexes, aged 1–8 years who had EBS-gen-sev with at least two new blisters per day were eligible for the study. The treatment consisted of oral soluble erythromycin for 3 months. A weight-based dosage was calculated for the children (< 10 kg, 250 mg per day; 10–15 kg, 500 mg per day; 15–25 kg, 750 mg per day; 25–35 kg, 1000 mg per day). Therapeutic success was defined as a decrease of at least 20% in the mean number of new blisters per day calculated over the course of 1 week at the end of treatment. At baseline, after 1 month and 3 months of treatment, the patients were seen for body examination, questionnaire, photographs, blood tests and bacteriological swabs. Itch severity and skin fragility were evaluated by parents on a visual analogue scale. At 5 months, we asked all parents for their opinion regarding the tolerability and efficacy of the treatment. Six patients (rather than eight as initially planned), with a mean age of 4 6 years, were selected for the study in the summer. Patient 5 took steroids during month 2 and antibiotics and steroids during month 4 for noncutaneous infectious disease. Patient 6 took antibiotics during month 1. Only patients 1–5 completed the study. Therapeutic success was achieved for patients 2, 3 and 5, with a mean decrease in the number of new blisters per day of 41% (Fig. 1). Itch severity and skin fragility scores did not show that oral erythromycin had any effect on these symptoms. Parents evaluated the efficacy of treatment as ‘good’ or ‘very good’ in two cases and ‘bad’ in three cases. Interestingly, one patient who achieved clinical success did not consider the treatment to be effective, even though the number of new blisters per day decreased by 24% at month 3 compared with baseline. The analysis of intermediate results at month 1 showed an increase in the number of new blisters per day for all patients. Five adverse events, which were not related to erythromycin, were reported during the study. The tolerability of the treatment was evaluated as ‘good’ by five patients and ‘poor’ by patient 6, who did not complete the study. At baseline, all six patients had skin colonization by Staphylococcus aureus and three had skin colonization by Streptococcus A (Fig. 2). Resistance to erythromycin was seen in only two of the patients with skin colonization by S. aureus and one of the Fig 1. The evolution of the number of new blisters per day for each patient at baseline and after 3 months of treatment with oral erythromycin.

Oral epigallocatechin-3-gallate for treatment of dystrophic epidermolysis bullosa: a multicentre, randomized, crossover, double-blind, placebo-controlled clinical trial

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis with severe blistering. No curative treatment is available. Scientific data indicated that epigallocatechin-3-gallate (EGCG), a green tea extract, might improve the phenotype of RDEB patients. In a multicentre, randomized, crossover, double-blind, placebo-controlled clinical trial, we evaluated a 4-month oral EGCG treatment regimen in 17 RDEB patients. We found that EGCG treatment was not more effective than placebo in modified intention to treat and per protocol analysis (n = 16; p = 0.78 and n = 10; p = 1 respectively). Tolerance was good. Specific organizational and technical difficulties of controlled randomized double-blind trials in EB patients are discussed.Trial registrationUS National Institutes of Health Clinical Trial Register (NCT00951964).

Late‐onset skin fragility in childhood: a case of junctional epidermolysis bullosa of late onset caused by a missense mutation in COL17A1

Conflicts of interest: I.G.-D. has received congress grants from Pfizer, Janssen and MSD. T.N.D. is a consultant and/or speaker for Abbott, Janssen-Cilag, LEO Pharma, MSD, Novo Nordisk and Pfizer. A.D.C. has received consultation fees from MSD and Abbott. C.B. has received research support from Epiderm, Abbott, Pfizer, Janssen-Cilag, MerckSerono and MSD. P.I.S. is principal investigator in many pharmaceutical initiated trials in her department, has received departmental research support from MSD and attended advisory board meetings for Leo Pharma and Janssen. L.N. is a member of the scientific board of the PSOLAR registry which is supported by Centocor. The remaining authors have no conflicts of interest to declare.

Mise au pointÉpidermolyses bulleuses héréditaires : protocole national de diagnostic et de soins (PNDS)Hereditary epidermolysis bullosa: French national guidelines (PNDS) for diagnosis and treatment

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.

Épidermolyses bulleuses héréditaires : protocole national de diagnostic et de soins (PNDS)

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.

Clinical and hemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations – data from the national paediatric French cohort CONAPE

Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed.

Epidermolysis bullosa simplex generalized severe induces a Th17 response and is improved by Apremilast treatment

Epidermolysis bullosa simplex generalized severe (EBS‐gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms.