Relationship between adherence to growth hormone therapy and growth.

Adherence to growth hormone (GH) therapy in children is variable and remains a problem which can significantly affect the response to GH treatment and future health and also have economic consequences. The response to GH treatment is not predictable at the start of treatment and depends on several factors, the main one being the diagnosis. Knowing the factors associated with poor adherence before treatment initiation can improve the response to treatment. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Childhood epidermal necrolysis and erythema multiforme major: a multicentre French cohort study of 62 patients.

INTRODUCTION: The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS: This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS: We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM. CONCLUSION: Clinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work-up in such situation. Sequelae affected both EN and EMM.

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial.

BACKGROUND: Baricitinib is an oral, selective, reversible Janus kinase 1/2 inhibitor approved in the European Union and Japan and under investigation in the United States for treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the impact of baricitinib plus background topical corticosteroids (TCS) on health-related quality of life (HRQoL), how AD symptoms impact work productivity and life functioning, and treatment benefit using patient-reported outcome (PRO) assessments in patients with moderate-to-severe AD previously experiencing inadequate response to TCS. METHODS: Adult patients with AD in BREEZE-AD7, a Phase 3, multicentre, double-blind trial, were randomised 1 : 1 : 1 to daily oral placebo (control) or baricitinib 4- or 2-mg plus TCS. PROs reported Week 1 through Week 16: Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-AD (WPAI-AD); Patient-Reported Outcomes Measurement Information System (PROMIS) Itch and Sleep measures, and Patient Benefit Index (PBI). Data were analysed using logistic regression (categorical) and mixed model repeated measures (continuous). PBI scores were analysed using analysis of variance. RESULTS: A total of 329 patients were randomised. Treatment with baricitinib 4-mg (N = 111) or 2 mg (N = 109) plus TCS led to rapid, statistically significant improvements [vs. TCS plus placebo (N = 109)] in DLQI ≥4-point improvement starting at Week 2 (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05), change from baseline in WPAI-AD presenteeism at Week 1 (4-mg plus TCS, P ≤ 0.01; 2-mg plus TCS P ≤ 0.05) and PROMIS itch interference at Week 2 (4-mg plus TCS P ≤ 0.01). Improvements were sustained through Week 16 for baricitinib 4-mg. Statistically significant improvements were observed at Week 16 for PBI global score (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05). CONCLUSIONS: Baricitinib plus TCS vs. placebo plus TCS showed significant improvements in treatment benefit at Week 16 and rapid significant improvements in HRQoL and impact of AD symptoms on work productivity and functioning through 16 weeks.

Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study.

BACKGROUND: Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD. OBJECTIVES: The objectives of this study were to describe the incidence and nature of dupilumab-induced OAEs and to assess the potential predisposing factors. PATIENTS AND METHODS: We conducted a prospective, single-centre, real-life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment. RESULTS: Forty-six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5-55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab-induced OAEs were associated with the following pre-existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3-31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8-40.6]), history of food allergy (OR 3.8 (95% CI: 1.002-14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2-91.3]). CONCLUSION: Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

Latent class analysis categorizes chronic hand eczema patients according to skin barrier impairment.

BACKGROUND: Chronic hand eczema (CHE) is the most common skin disorder affecting the hands. It causes major physical and psychological burden for patients. Classification of CHE remains challenging because of its aetiological and clinical heterogeneity. OBJECTIVES: Using latent class analysis (LCA) on a large categorical data set, our aim was to identify distinct phenotypes in a cohort of unselected CHE patients based upon clinical, genetic, molecular and physical parameters of the affected skin. METHODS: We performed two independent LCA on a cohort of 71 well-characterized patients that initially integrated clinical severity, total immunoglobulin E plasma level, transepidermal water loss, hydration index, interleukin(IL)-8 lesional skin level, Staphylococcus (aureus and epidermidis) colonization, FLG genotype and the expression (mRNA) of genes involved either in the filaggrin degradation and the natural moisturizing factor synthesis, the cornified envelope formation, the tight junctions' structure and the desquamation process, or encoding antimicrobial peptides and chemokines. RESULTS: The first LCA categorized patients into a group displaying high severity of CHE, high skin barrier impairment, high Staphylococcus colonization, high IL-8 skin level and high frequency of mutation in the FLG gene and a second group with opposite characteristics. The second LCA identified two independent groups of patients categorized by their low or high level of skin barrier impairment and corresponding changes in the expression of the related genes. CONCLUSIONS: Our study suggests that the degree of skin barrier dysfunction is the most important parameter to discriminate CHE patients and probably plays a pivotal role in the pathogenesis of the disease whatever the aetiological factors. As far as we know, this is the first study to address this topic using a statistical categorization method without preconception.

[French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults]. / Recommandations françaises sur l'utilisation des traitements systémiques chez les patients adultes atteints de psoriasis modéré à sévère.

AIM: These guidelines for the treatment of psoriasis have been developed by the Psoriasis Research Group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. METHODS: Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in generating the algorithms. RESULTS: We propose two new algorithms to assess therapeutic response, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

Long-term continuation with secukinumab in psoriasis: association with patient profile and initial psoriasis clearance.

BACKGROUND: There are limited data regarding the long-term continuation with biological therapy for patients with psoriasis. In particular, the reasons for secukinumab discontinuation have not been thoroughly investigated. AIM: To better ascertain the real-life continuation of secukinumab in psoriasis, we conducted a retrospective study to evaluate the incidence, causes and factors of secukinumab discontinuation in patients with psoriasis. METHODS: All patients treated with secukinumab for psoriasis in the Department of Dermatology (Toulouse University and Larrey Hospital, Toulouse, France), between September 2011 and June 2017, were enrolled in the study. RESULTS: Of the 91 patients in the study, 22 (24.2%) discontinued secukinumab. In 14 (15%) patients, the discontinuation was due to loss of efficacy. Two patients stopped treatment because they planned a pregnancy and five patients stopped because of adverse events. A longer disease duration (P = 0.01) and presence of palmoplantar psoriasis (P = 0.01) seem to be predictive factors for treatment failure. Patients reaching 90 or 100% improvement in Psoriasis Area and Severity Index (PASI90 and PASI100, respectively) at weeks 12-16 had a lower risk of long-term treatment discontinuation compared with patients who had less complete clearance (P = 0.04). CONCLUSION: Long-term persistence of secukinumab appears to be good, as only 24.2% (n = 22) of the patients in this study discontinued secukinumab over the follow-up period. Loss of efficacy prompted discontinuation in about 14% of patients by the 2-year follow-up. Persistence appears to be lower in patients with palmoplantar psoriasis and in patients previously exposed to many systemic treatments. Optimal therapeutic response at 12-16 weeks as defined by reaching PASI90-100 seems to be predictive of long-term treatment persistence.