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.

Value of Doppler ultrasound scans in deciding whether to treat infantile haemangioma with oral propranolol.

BACKGROUND: Oral propranolol (Pr) must be administered until the end of the proliferation phase of infantile haemangioma (IH). This phase may be difficult to assess, particularly where a deep component is involved. Doppler ultrasound scans (DUS), which identify vascular activity (VA), could assist the clinician in making the correct therapeutic decision (CTD). PATIENTS AND METHODS: All children with IH treated with Pr for at least 3 months and up to the age of 9 months, and who also underwent DUS, were enrolled in this retrospective, single-centre, observational study. The quality of DUS as a binary diagnostic test for IH proliferation was assessed, together with its value in deciding whether to discontinue Pr (at the end of the presumed proliferation phase) or resume this drug (in the case of suspected recurrence). RESULTS: A total of 29 children were enrolled and 45 DUS were performed. Thirty-nine (87%) DUS were of high quality (80% sensitivity, 95% specificity) and made a major, moderate, or minimal contribution to the CTD in respectively 20%, 60% and 7% of cases. DISCUSSION: DUS proved to be a high-value tool. They were essential in some cases of IH, mainly periocular and localised forms, and those involving deep components, in which the question of discontinuing Pr arose (age>1 year) and where clinical examination had not been sufficient to make the CTD. Furthermore, in the vast majority of cases, they provide a helpful examination and complement clinical findings in terms of patient follow-up and reaching a CTD. CONCLUSION: DUS is an effective and complementary tool to clinical investigation.

Factors influencing quality of life in children with low-flow vascular malformations: a qualitative study using focus groups.

BACKGROUND: Very few studies have evaluated the quality of life (QoL) of children suffering from low-flow vascular malformations. This is the first study investigating the influencing factors. OBJECTIVES: To identify the factors influencing QoL in children with low-flow vascular malformations. METHODS: We conducted a qualitative study employing focus group interviews (Clinical Trials Number: NCT03440827). The study was a prospective, interventional, non-comparative, multicentre study performed in four expert centres for vascular anomalies. Qualitative data about personal experiences, feelings, difficulties, needs and various factors influencing behaviours were collected. Theme-based content analysis (manual and specialist textural software guided) were used to analyse the verbatim transcripts of all focus group sessions. Manual qualitative discourse analysis was performed to identify the different themes and categories. Informatics' analyses were subsequently performed for each individual category. RESULTS: Ten focus groups (26 individuals including 10 children aged 11 to 15 years) were conducted until saturation. Influencing factors were related to 4 categories: medical care, self-image, social impact on daily activities and challenging social relationships. These factors were responsible for intrafamily upheavals and may lead to future identity-building problems. CONCLUSIONS: This study provides an essential framework from which physicians can develop strategies to improve patient care and quality of life. These data may also be useful to develop specific age-sensitive QoL questionnaires.

Management of congenital ichthyoses: European guidelines of care, part two.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

Management of congenital ichthyoses: European guidelines of care, part one.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.

[Multiple hypochromic or achromic macules in children and risk of tuberous sclerosis]. / Macules hypochromiques ou achromiques multiples de l'enfant et risque de sclérose tubéreuse de Bourneville.

AIM: To describe in a large paediatric cohort the characteristics of hypopigmented and depigmented (hypochromatic and achromic) macules with no clear diagnosis but potentially evocative of tuberous sclerosis (TS). PATIENTS AND METHODS: This was a retrospective multicentre study performed between 2010 and 2017 at a reference centre for rare skin diseases; it included all children consulting for hypochromic and achromic macules. A descriptive analysis was made of the characteristics of macules with no clear diagnosis, enabling them to be classified in three secondary groups: TS certain, TS ruled out, TS uncertain. RESULTS: Of the 3300 children seen during this 7-year period 7,265 were consulting for hypochromic or achromic macules, with no clear diagnosis in 18 cases: 7 girls and 11 boys of median age at 7.21 years (range: 4 months to 16 years and 7 months). The lesions were congenital in 7 cases. The number of macules varied, with over 20 in some cases. The majority were in the form of ash-leaf spots, followed by the oval form. Two children were diagnosed at clinical examination, and 16 underwent it is not examinations, resulting in a diagnosis of certain ST in 6 of these cases. No particular characteristics of the macules appeared to guide the clinical examination towards ST or isolated lesions. Café-au-lait spots were more frequent in the group in which ST was ruled out than in the other two groups: 67% vs. 33% and 33%. Neurologic involvement was more common in children with certain or uncertain ST than in children in whom ST was ruled out (83% and 67% vs. 11%). CONCLUSION: No identified characteristics of stains enabled the clinical examination to confirm or rule out tuberous sclerosis. Screening for acute any signs of ST is essential. Diagnostic efficacy is enhanced by additional exams.

[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.

Factors associated with delayed referral for infantile hemangioma necessitating propranolol.

BACKGROUND: Oral propranolol is the gold standard to treat infantile hemangiomas. There is better efficacy and a lower risk of sequelae if therapy is started before the end of the growth phase, but most children are referred too late. Herein, we report the first study to investigate the delay and its associated factors when referring infants with infantile hemangiomas that need propranolol therapy. OBJECTIVES: The primary objective was to determine the delay in referral (time between age at referral [first phone contact] and the optimal age for referral (fixed at 75 days). The second objective was to determine the impact of weighted factors associated with delayed referral assessed by logistic regression performed on two subgroups (referral ≤75 vs. >75 days). METHODS: Monocentric, retrospective, observational study included infants with infantile hemangiomas treated with oral propranolol between August 2014 and May 2017. RESULTS: Eighty-two children (83% females) were included. Before referral, 81 (99%) children had seen another physician (a paediatrician in 67% of cases). Median age at referral was 99 days [2-478] and 63% phoned after 75 days. Median age at the first visit was 111 days [2-515], and median age when propranolol was started was 128 days [32-541]. After adjustment, in multivariate analyses, location on the lips (OR (CI 95%): 4.21[1.19-14.89]) and superficial hemangioma (OR (CI 95%): 4.19 [1.55-11.34]) emerged as the most significant factors to influence referral before 75 days. CONCLUSIONS: This study adds to our understanding regarding delayed referral and has identified targets for future information campaigns.

Stay in NICU and infantile haemangioma development.

BACKGROUND: Infantile haemangiomas (IHs) are more frequent in low birth weight babies, especially premature. OBJECTIVE: To compare the characteristics of infants with IHs who stayed in neonatal intensive care unit (NICU) vs. those with IHs who did not. METHODS: Prospective observational multicentric study. Consecutive infants consulting for IHs in two departments of paediatric dermatology were included and a questionnaire specifically designed was filled for each patient. To identify factors associated with hospitalization in NICU vs. no hospitalization in NICU, we conducted univariate logistic regression analyses. RESULTS: A total of 210 infants with 323 IHs were included (56 boys, 154 girls, F/M sex ratio 2.75/1); 27 stayed in NICU, whereas 183 did not. Limbs involvement and multiple IHs were more frequent in NICU infants. Similarly, infants who had stayed in NICU had an earlier onset of their IH. Multiple IH was more frequent in infants with a history of congenital onset of IH. CONCLUSION: Infants staying in NICU and those with congenital lesion are at risk for specific type and involvement of their IH and should be early addressed to a dermatologist in case of suspicion of IH to provide them an early diagnosis and to start a treatment if necessary as soon as possible.

Treatment of port wine stains with pulsed dye laser and topical timolol: a multicenter randomized controlled trial.

BACKGROUND: Neoangiogenesis occurs within days following laser treatment of port wine stains (PWS), and plays a central role in treatment failures. Topical use of timolol can significantly reduce the production of vascular endothelial growth factor in vitro, and in animal models. OBJECTIVES: The aim of this study was to assess the efficacy of topical timolol in combination with pulsed dye laser (PDL) treatment, compared with PDL alone, for treating PWS. METHODS: This was a prospective multicenter controlled trial performed in children with PWS of the face who had not previously received laser treatment. After randomization, one group was treated with PDL alone, and the other with PDL followed by twice daily applications of timolol gel. Three laser sessions were performed at 1-month intervals with fixed parameters. The evaluation was performed on standardized pictures by two independent physicians blinded to the treatment received. The primary endpoint was marked or complete improvement of the PWS [Investigator Global Assessment (IGA) 3 or 4] 1 month after the third session. RESULTS: Twenty-two children were included. Two patients were lost to follow-up. There was no difference in the success rate between the two groups (IGA 3 or 4 observed in one of 10 patients and two of 12 patients, for PDL alone, and for PDL associated with topical timolol, respectively; P = 1·0). No side-effect related to the application of topical timolol was observed. CONCLUSIONS: The addition of timolol gel for preventing neoangiogenesis failed to significantly improve the efficacy of PDL treatment of PWS.

Propranolol-resistant infantile haemangiomas.

BACKGROUND: Propranolol is now widely used to treat severe infantile haemangiomas (IHs). Very few cases of propranolol-resistant IH (PRIH) are mentioned in the literature. OBJECTIVES: To describe the characteristics of PRIHs. METHODS: A national, multicentre, retrospective, observational study was conducted from February 2011 to December 2011. All patients with PRIH evaluated by the members of the Groupe de Recherche Clinique en Dermatologie Pédiatrique from 1 January 2007 to 1 December 2011 were eligible. RESULTS: Among 1130 patients treated with propranolol for infantile haemangioma, 10 (0.9%) had PRIHs. Haemangioma propranolol resistance was observed at all ages during early childhood and at any proliferation stage. CONCLUSIONS: PRIH is a rare phenomenon that raises questions and merits further investigation.

[What's new about infantile hemangiomas?]. / Quoi de neuf dans les hémangiomes infantiles ?

Infantile hemangioma is the most common vascular tumor of childhood. This benign tumor appears during the first weeks of life, grows during the first months (endothelial proliferation) and then involutes slowly and spontaneously until resolution (possibly with sequelae) which is observed after several years. Although they are always benign tumors, infantile hemangiomas can cause complications. Regarding their location or size, infantile hemangiomas can be life or function-threatening. They are also painful when ulcerated and can cause permanent disfigurement or long-term adverse psychological consequences. Since 2008 and the serendipitous discovery of the efficacy of propranolol in the treatment of infantile hemangiomas, systemic propranolol therapy has been widely used, with a very interesting benefits/risks balance. It has progressively superseded general corticosteroid therapy. A Compassionate Use Program (CUP) for systemic propranolol therapy has been developed in France and represents nowadays the first-line use for the vast majority of French prescribers.

Factors influencing quality of life in patients with inherited ichthyosis: a qualitative study in adults using focus groups.

BACKGROUND: There is limited information regarding quality of life in patients with inherited ichthyosis. OBJECTIVES: To identify factors influencing quality of life in patients with inherited ichthyosis. METHODS: The study used focus groups and involved adult patients suffering from inherited ichthyosis from three French hospital centres. Group discussions were conducted by two facilitators and were continued until data saturation was reached. The verbatim transcripts were analysed independently by two investigators. Categories considered as key factors in the modulation of quality of life were negotiated until agreement was obtained. RESULTS: Data saturation was reached after the fifth group. A total of 25 patients affected by various forms of ichthyosis attended these focus groups. The identified factors influencing quality of life were related to physical health, daily life, relations with others or oneself. However, together with difficulties related to ichthyosis, patients also underlined some positive aspects of the disease and described specific measures used to improve their quality of life. CONCLUSIONS: This is the first study investigating the different factors that could impact quality of life in patients with ichthyosis. This provides an essential framework from which physicians can develop strategies to improve patient care and quality of life and to develop a specific quality of life questionnaire.

Desloratadine relieves nasal congestion and improves quality-of-life in persistent allergic rhinitis.

BACKGROUND: Symptoms of allergic rhinitis (AR), particularly nasal congestion, can impair quality-of-life (QoL). However, only a modest correlation exists between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, suggesting that both be evaluated for a complete assessment of health. METHODS: Subjects with a > or =2-year history of moderate-to-severe AR to dust mite or cat dander were randomized to desloratadine 5 mg/day (n = 293) or placebo/day (n = 291) for 28 days. Primary endpoint was change from baseline in a.m./p.m. nasal congestion score. Secondary outcomes included change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores (completed on days 1, 7, and 28). RESULTS: The Allergic Rhinitis and its Impact on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99% of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal congestion score, observed from day 8 onward, significantly favored desloratadine (P = 0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and RQLQ scores after 1 week and at treatment end (P < 0.05). Improvements in 5 of 7 RQLQ domain scores exceeded the minimal important difference. On days 7 and 28, desloratadine was also significantly superior to placebo in mean change from baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P < or = 0.01). Symptomatic benefit was primarily driven by improvement in nasal congestion and rhinorrhea. CONCLUSIONS: Desloratadine 5 mg/day significantly improved symptoms associated with PER, including nasal congestion, and provided significant improvement in QoL after 1 week of treatment.

How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of life.

BACKGROUND: Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second-generation H(1)-antihistamines (proven to control CIU symptoms) should be taken long-term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves or better maintains QoL in CIU: desloratadine (DL) daily or PRN. METHODS: Subjects with CIU initially responding to DL 5 mg/day for 4 weeks were randomized for an additional 8 weeks, to DL 5 mg/day (arm 1: 'continuous', n = 46) or to DL only on days when urticarial wheals were present (arm 2: "PRN", n = 60). To ensure blinding, treatment was presented in both arms as a combination of daily treatment (arm 1: DL; arm 2: placebo), plus a "rescue" tablet (arm 1: placebo; arm 2: DL) to be taken only in case of symptoms. The main outcome measure was QoL assessed by the VQ-Dermato, a validated French QoL instrument, and the Dermatology Life Quality Index (DLQI). RESULTS: At 4 and 8 weeks after randomization, subjects taking continuous DL showed statistically significant improvements in VQ-Dermato Global Index score (P = 0.001 and P = 0.016, respectively) and dimension scores for daily living activity, mood state, and social functioning vs subjects taking DL PRN. Improvement in DLQI score at Week 4 was also significantly greater with continuous DL (P = 0.001). CONCLUSION: Continuous daily therapy with DL 5 mg is a better regimen than PRN treatment to maintain or improve QoL in subjects with CIU.

[Patient preference survey on the lack of taste and odor of Nasonex nasal spray. Which impact on compliance to treatment?]. / Enquête de préférence patients sur l'absence de saveur et d'odeur du Nasonex en pulvérisation nasale. Quel impact sur l'observance du traitement ?

In order to assess the acceptability of a new scent-free formulation of mometasone furoate (Nasonex) among allergic rhinitis patients, who already have been treated by the scented formulation of Nasonex, a phone survey was performed with a sample of 216 patients recruited by Nasonex GP's prescribers and pharmacists. The aim of this survey is to assess the diagnosis modalities, the allergic rhinitis characteristics and associated symptoms in one hand and in the other hand, the main reasons which led them to prefer a new scent-free formulation, in comparison with the only commercialized scented mometasone furoate (Nasonex) at the time when this survey was conducted. The impact of unscented Nasonex on patient's compliance to treatment was also assessed. This survey confirms that the GP is the key actor who usually establish the allergy diagnosis and the interrogatory is the principle method used. The prick test was more often and significantly used in 35% of the perennial rhinitis instead of 19% in seasonal allergic rhinitis (p < or = 0.05). When the diagnosis of allergy was established by an allergologist, 89% of them used a prick test. In this survey, asthma was associated in 24% of the patients, particularly in who suffering from perennial allergic rhinitis. 85% of patients rate their smell as globally good. 75% of the treated patients were interested by the new unscented formulation of Nasonex, regardless of the type of their rhinitis, seasonal or perennial. About 60% of patients stated that the lack of odor will led them to be more compliant to their treatment.