Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014-2021 French Ouest DataHub.

BACKGROUND: The factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. OBJECTIVES: To identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. METHODS: We performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. RESULTS: A total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0-78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02-0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. CONCLUSION: The risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.

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.

Characteristics of children and adolescents with atopic dermatitis who attended therapeutic patient education.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Therapeutic patient education (TPE) has been demonstrated to be effective in AD in reducing disease severity and improving coping and quality of life. OBJECTIVES: To describe the sociodemographic and clinical characteristics of children and adolescents with AD who had attended TPE sessions, as well as the characteristics of their parents, and compare them with those who did not attend TPE. METHODS: Parents of children with AD aged 6-17 years old were recruited from a representative sample of the French population contacted by e-mail. Sociodemographic data and clinical information were collected in patients and parents. Clinical severity was assessed by parents using a proxy version of the Patient-Oriented Eczema Measure (POEM). Attendance to TPE sessions was assessed by the following question 'did your child or one or both parents attended TPE for AD?'. Also, the number of sessions was recorded. Determinants of TPE attendance were evaluated by univariable and multivariable analyses. RESULTS: Data were collected on 1063 parents and children with AD. A total of 131 (12.3%) children and/or parents attended TPE sessions. Most of them attended 2-5 TPE sessions. In that group, there were 85 boys (64.9%), and severity evaluated by POEM was mild in 29.8%, moderate in 52.7% and severe in 17.6% of patients. In the multivariable model, attending TPE sessions was significantly associated with sex of the child (boy vs. girl), consultation with a dermatologist or a paediatrician, high clinical severity and presence of AD in parents. CONCLUSIONS: Despite recommendations, the use of TPE in children with AD is still low in France. There is a need for implementing such programmes in the management of the disease, in particular when the disease is severe.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

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.

[Clinical and evolutionary characteristics of a child with aquagenic keratoderma: A retrospective study of 12 patients]. / Caractéristiques cliniques et évolutives de la kératodermie aquagénique de l'enfant : étude rétrospective de 12 cas.

INTRODUCTION: Aquagenic keratoderma (AK) is a rare condition characterized by wrinkled and edematous appearance of the skin of the hands occurring within minutes of immersion in water. Other than in a setting of cystic fibrosis, AK has rarely been reported in children, with only 13 clinical cases on record. Many clinicians are unfamiliar with AK and have fears relating to the association with cystic fibrosis The aim of this study is to describe the characteristics and to discuss management of the disease. METHODS: Retrospective, multicentre study, including children aged under 16 years presenting AK. RESULTS: 12 children were included. KA started at a mean age of 9.25 years (range: 20 months to 15 years). Clinical appearance and mode of onset were classical, with the palms being more severely affected than the soles. Pruritus or pain were reported in six cases. The median impact on daily life was 1.5/10. Some of the children underwent investigations: two had a negative sweat test, three had molecular analysis of the gene CFTR: one was negative and two had a heterozygote mutation. The course of the disease was variable: eight stabilizations, two exacerbations, one cure and one improvement. DISCUSSION: This is the first series on childhood KA. Clinical characteristics were similar to those seen in adults. Impact was moderate and the disease course was variable. Systematic medical check-up for cystic fibrosis does not appear warranted in children since to date, cystic fibrosis has not been diagnosed in any patients presenting AK alone. CONCLUSION: AK is rare in children and should not cause erroneous concern, and improvement can occur.

[DRESS syndrome and agranulocytosis, a rare combination]. / Syndrome d'hypersensibilité médicamenteuse et agranulocytose, une association rare.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe toxidermia that can lead to death from multivisceral failure. We report a case of DRESS associated with febrile agranulocytosis in a child. OBSERVATION: An 8-year-old child was hospitalized for diffuse maculopapular exanthema with edema of the extremities and face associated with cheilitis and febrile agranulocytosis. This symptomatology began 1month after the introduction of carbamazepine for partial epilepsy. The clinical picture was a multisystemic disease with colitis, interstitial pneumonitis, hepatic cytolysis, and hepatocellular insufficiency. HHV7 viral reactivation and increased eosinophils (20%) in the myelogram were demonstrated, providing the diagnosis of DRESS. The progression was favorable after carbamazepine therapy was stopped and systemic corticosteroids were administered. DISCUSSION: DRESS syndrome is a disorder that is unfamiliar to pediatricians. Its association with agranulocytosis is rare and the absence of hypereosinophilia contributed to diagnostic difficulties in this case. The multisystemic failure, the reactivation of HHV7, the increase of eosinophils in the myelogram, and the favorable progression under systemic corticosteroid therapy contributed greatly to the diagnosis. A cutaneous biopsy was not considered necessary for the diagnosis in the case reported herein. CONCLUSION: DRESS syndrome is rarely associated with agranulocytosis, but its diagnosis must be quickly raised so that the incriminated drug can be interrupted.

[Oral care recommendations for patients with oral autoimmune bullous diseases]. / Recommandations pour la prise en charge buccodentaire des patients atteints de maladies bulleuses auto-immunes avec atteinte buccale.

BACKGROUND: Autoimmune bullous diseases (AIBD) may cause chronic oral lesions that progress insidiously. AIMS: To provide recommendations for optimal oral-dental management of patients presenting AIBD with oral involvement. PATIENTS AND METHODS: In the absence of scientific studies with high levels of proof, these recommendations have been drawn up at two meetings by a committee of experts on AIBD comprising 7 dermatologists, 1 stomatologist, 1 maxillofacial surgeon, 2 odontologists and 4 parodontologists. RESULTS: The oral lesions associated with AIBD may be classified into three grades of severity: severe (generalised erosive gingivitis affecting at least 30% of dental sites), moderate (localised erosive gingivitis affecting less than 30% of dental sites) and controlled (no erosive oral lesions). Good oral-dental hygiene suited to the severity of the oral lesions, must be practised continually by these patients so as to avoid the formation of dental plaque, which aggravates symptoms. Dental and parodontal care must be considered in accordance with the severity grade of the oral lesions: in severe cases, the dental plaque must be eliminated manually with a curette, but several types of care (descaling, treatment for tooth decay, non-urgent extractions, etc.) must be suspended until the grade of severity is moderate or until the disease is stabilised.

[Impact of sex and age on the clinical and epidemiological aspects of childhood psoriasis: Data from a French cross-sectional multicentre study]. / Impact de l'âge et du sexe sur les aspects cliniques et épidémiologiques du psoriasis de l'enfant. Données d'une étude transversale multicentrique française.

BACKGROUND: The 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 METHODS: A 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: <2 years; children: ≥2 years and <13 years; adolescents≥13 years. The information collected included demographic data, clinical, epidemiological, and therapeutic aspects of the psoriasis, as well as analysis of comorbidities. RESULTS: Three hundred and thirteen children were included: 27 (8.6%) infants, 207 (66.1%) children, and 79 (25.2%) adolescents. Plaque psoriasis was the most frequent clinical type of psoriasis seen in children and adolescents (>41%), but it accounted for only 25.9% of psoriasis of infants (P<0.0001). Napkin psoriasis (37.0%) and inverse psoriasis (22.2%) were the most common forms of psoriasis seen in infants and were described significantly more frequently in this group than in the two other groups (P<0.003). Nail involvement was more common in adolescents (37.2%, P=0.03) and children (32.9%) than in infants (14.8%) and affected boys more than girls (43.6% vs 22.0%, P<0.0001). Girls presented scalp psoriasis more frequently (17.7% vs 8.7%, P=0.02). Local vitamin-D treatment and systemic therapies were used more frequently in children and adolescents than in infants. There was no significant difference for treatment use, including for acitretin, according to gender. DISCUSSION: Plaque psoriasis was the most common clinical type of psoriasis in children but affected less than 50% of the children. Age had a significant impact on extra-cutaneous skin disorders and on treatment used, while sex had little incidence. The frequency of comorbidities was not affected by age. CONCLUSION: Childhood psoriasis thus presents specific characteristics dependent on the age of the child. The results of studies exclusively dealing with adults cannot be extrapolated to children.

Increased prevalence of psoriasis in patients with coronary artery disease: results from a case-control study.

BACKGROUND: The incidence of myocardial events has been reported to be increased in patients with psoriasis. OBJECTIVES: To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD). METHODS: We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included. RESULTS: Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42-4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99-3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50-6·25). CONCLUSIONS: The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.