Effectiveness of a nurse-led one-to-one education programme in addition to standard care in children with atopic dermatitis: a multicentre randomized control trial.

BACKGROUND: Therapeutic patient education (TPE) is recommended for children with atopic dermatitis (AD), but no consensus has been reached on the optimal tailoring of delivery. While repeated multidisciplinary group education sessions have shown effectiveness, the benefits of one-on-one educational interventions led by nurses for children with AD have not yet been assessed. OBJECTIVES: To assess the benefits of additional, well-structured, 1-h nurse-led individual TPE interventions in children with AD and their families compared with standard care alone. METHODS: Children with moderate-to-severe AD and their parents were randomized to receive a 1-h nurse-led education session in addition to standard care vs. standard care alone. The primary outcome was the area under the curve (AUC) of the SCORing of Atopic Dermatitis index (SCORAD) from baseline to week 24 (lower AUC values represent better long-term control of the disease). RESULTS: In our study, 176 patients were randomized across 11 centres, and 153 were included in the full analysis set. The mean (SD) age was 4.47 (4.57) years. By week 24, there were no significant differences in the AUCs of the SCORAD between the two groups (P = 0.3). Secondary outcomes including patient-reported severity and quality of life [AUCs of the patient-oriented SCORAD (PO-SCORAD) and Infants' Dermatitis Quality of Life Index (IDLQI), Children's Dermatitis Quality of Life Index (CDLQI) and Family Dermatitis Quality of Life Index (FDLQI)] were not significantly different between the two groups. The only significant change observed in the intervention group, when compared with the one receiving standard care, was a decrease in topical steroid phobia, as assessed by the topical corticosteroid phobia (TOPICOP) score. Prespecified subgroup analyses showed that disease severity in the intervention group was significantly lower throughout the study, compared with the standard-care group when participants had moderate AD at baseline (n = 47); while participants with severe AD at baseline (n = 106) did not show benefit from the intervention. Participants showed no additional benefit from the intervention regardless of age group. CONCLUSIONS: This study did not show any additional effectiveness, in long-term severity control, of a 1-h nurse-led TPE intervention in children with AD treated with standard care, compared with those treated with standard care alone. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for patients in the subgroup with moderate AD.

Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study.

BACKGROUND: Studies demonstrating the potential utility of reflectance confocal microscopy (RCM) have been performed under experimental conditions. OBJECTIVE: To provide an overview of RCM practice in real-life. METHODS: A multicenter, prospective study carried out in 10 university dermatology departments in France. RESULTS: Overall, 410 patients were enrolled. One-half of the patients (48%) were referred by private practice dermatologists. They were referred for diagnosis (84.9%) or presurgical mapping (13%). For diagnosis, the lesions were located on the face (62%), arms and legs (14.9%), and trunk (13.6%), and presurgical mapping was almost exclusively on the face (90.9%). Among those referred for diagnosis, the main indication was suspicion of a skin tumor (92.8%). Of these, 50.6% were spared biopsies after RCM. When RCM indicated surgery, histology revealed malignant lesions in 72.7% of cases. The correlation between RCM and histopathology was high, with a correlation rate of 82.76% and a kappa coefficient of 0.73 (0.63; 0.82). LIMITATIONS: This study was performed in the settings of French tertiary referral hospitals. CONCLUSION: This study shows that in real-life RCM can be integrated into the workflow of a public private network, which enables a less invasive diagnostic procedure for patients.

Accurate diagnosis of acute hemorrhagic edema of infancy: a French multicenter observational study.

The purpose of the study is to highlight clinical signs that are either suggestive of or against the diagnosis of AHEI to improve diagnosis and management. The medical records of children under 3 years old diagnosed with AHEI were retrospectively reviewed. Clinical data and photographs were reviewed by three independent experts, and the cases were classified as probable, doubtful, or unclear AHEI. Of the 69 cases of children diagnosed with AHEI included in 22 centers, 40 were classified as probable, 22 as doubtful, and 7 as unclear. The median age of patients with probable AHEI was 11 months [IQR 9-15], and they were in overall good condition (n = 33/40, 82.5%). The morphology of the purpura was targetoid in 75% of cases (n = 30/40) and ecchymotic in 70% of cases (n = 28/40) and affected mostly the legs (n = 39/40, 97%), the arms (n = 34/40, 85%), and the face (n = 33/40, 82.5%). Edema was observed in 95% of cases and affected mostly the hands (n = 36/38, 95%) and feet (n = 28/38, 74%). Pruritus was absent in all patients with probable AHEI and described for 6/21 with doubtful AHEI (29%). AHEI was the original diagnosis in only 24 patients (n = 24/40, 60%). The major differential diagnoses were purpura fulminans and urticaria multiforme.  Conclusion: AHEI, which the diagnosis is made on clinical findings, is often misdiagnosed. Purpuric lesions localized on the face/ears, arms/forearms, and thighs/legs with edema of the hands without pruritus in a young child with a good overall condition are highly suggestive of AHEI. What is Known: •Acute hemorrhagic edema of infancy (AHEI) is a cutaneous leukocytoclastic vasculitis affecting children under 3 years old. •Appropriate diagnosis is important to distinguish this benign disease from more serious diseases to avoid investigations and treatments, iatrogenic harm and unnecessary follow-up. What is New: •AHEI is an uncommon disorder often misdiagnosed by pediatricians and dermatologists. •Purpuric lesions localized on the face/ears, arms/forearms, and thighs/legs with edema of the hands without pruritus in an infant with a good overall condition are highly suggestive of AHEI.

Intramuscular capillary-type hemangioma: Diagnosis, treatment, and outcomes. A French multicentric retrospective study of 66 cases.

PURPOSE: Intramuscular capillary-type hemangiomas (ICTHs) are rare entities, belonging to the group of intramuscular "hemangiomas." The diagnosis remains challenging. We aimed to assess the diagnostic criteria, treatments and outcomes of ICTHs. METHODS: This retrospective study collected all cases of ICTH followed up in 9 French hospital centers, reviewed by an adjudication expert group. RESULTS: Among 133 patients screened, 66 with ICTH were included. The median age of patients at diagnosis was 28.0 years, interquartile range (21.0---36.0). The lesion, mainly presenting as a gradually increasing mass (83.9%), was painless (88.9%) and was located in the head and neck (42.4%). MRI (available in all cases) mainly revealed a well-delineated lesion, isointense to the muscle on T1-weighted images, with enhancement after contrast injection; hyperintense on T2-weighted images; and containing flow voids. Among the 66 cases, 59 exhibited typical ICTH features and 7 shared some imaging features with arteriovenous malformations. These latter were larger than typical ICTHs and more painful and appeared on imaging as less well delimited and more heterogeneous tissue masses, with larger tortuous afferent arteries, earlier draining vein opacification and mild arteriovenous shunting. We propose to name these lesions arteriovenous malformation (AVM)-like ICTH. Pathological reports were similar in typical and AVM-like ICTH, showing capillary proliferation with mainly small-size vessels, negative for GLUT-1 and positive for ERG, AML, CD31 and CD34, with low Ki67 proliferation index (<10%), and adipose tissue. The most frequent treatment for ICTH was complete surgical resection (17/47, 36.2%), preceded in some cases by embolization, which led to complete remission. CONCLUSIONS: ICTH can be diagnosed on MRI when it is typical. Biopsy or angiography are required for atypical forms.

Biologics combined with conventional systemic agents for the treatment of children with severe psoriasis. Real-life data from the BiPe cohorts and a practice survey among French and Italian pediatric dermatologists.

Combined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We evaluated the use of combinations of conventional systemic therapies and biologics in children with psoriasis in daily practice. This two-part study used data from the 170 children in the Franco-Italian BiPe cohorts to evaluate the use, efficacy, and safety of combined conventional systemic-biologic therapies, and from a survey carried out among French and Italian dermatologists to better understand the reasons for using or avoiding these combinations. In total, 33 children (19.4%) from 13 dermatology centers received 48 combined conventional systemic-biologic therapies (cumulative duration: 43.6 years), including three triple combination therapies (acitretin-methotrexate, with a TNF-alpha inhibitor). A total of 14 different combinations were used, most frequently etanercept-acitretin (n = 10), adalimumab-acitretin (n = 7), adalimumab-methotrexate (n = 5), and ustekinumab-methotrexate (n = 5). The combined therapies were started at biologic initiation in 41 cases (85.4%), and after a period of biologic monotherapy in the remaining 7 cases. Mean PGA and PASI scores decreased between baseline and M3 with all the combinations used. Four serious adverse events were reported, all with favorable outcomes. The survey was completed by 61 dermatologists: 39 (63.9%) had previously used or planned to use the combined therapies, most commonly TNF-alpha inhibitors with acitretin or methotrexate. The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. Combined therapies have been used frequently in the treatment of childhood psoriasis, in a range of clinical situations and in variable drug combinations, without significant toxicity. Although the use of these combined therapies needs to be clarified in future management guidelines, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis, and recalcitrant disease.

Perialar intertrigo in children and adolescents: A multicenter prospective study of 41 cases.

BACKGROUND/OBJECTIVES: We observed isolated cases of perialar intertrigo in children and teenagers that did not appear to correspond to any known clinical entity. The objective of this study was to describe the clinical features of this dermatosis and the clinical characteristics of the patients. METHODS: We conducted a prospective, multicenter cohort study in France from August 2017 to November 2019. All the patients under 18 years of age with chronic perinasal intertrigo were included. A standardized questionnaire detailing the clinical characteristics of the patients and the description of the intertrigo. If possible, a Wood's lamp examination of the intertrigo was done. RESULTS: Forty-one patients were included (25 boys and 16 girls, average age: 12.1 years). Intertrigo was bilateral in 38 patients (93%). The majority of patients had no symptoms (54%). Pruritus was present in 39% of cases. Orange red follicular fluorescence was present in the perialar region on Wood's light examination in 78% of cases with active fluorescence. The presumptive diagnoses suggested by the investigators were acne (24.4%), seborrheic dermatitis (19.5%), rosacea (9.8%), psoriasis (9.8%) and perioral dermatitis (7.3%). No diagnosis was proposed in 22% of the cases. CONCLUSIONS: We describe a previously undescribed clinical sign which is characterized by a chronic bilateral erythematous intertrigo located in the perialar region. It can be isolated or associated with various facial dermatoses.

Effectiveness and Safety of Adalimumab, Etanercept and Ustekinumab for Severe Psoriasis in Children Under 12 Years of Age: A French-Italian Daily Practice Cohort (BiPe Jr).

INTRODUCTION: Biological therapies are valuable treatments for severe psoriasis. Children aged under 12 years are underrepresented in therapeutic trials for these drugs. The objective of the 'BiPe Jr' cohort study was to evaluate the drug survival, effectiveness, tolerance and switching patterns of biological therapies in children under 12 years of age with psoriasis. METHODS: We conducted a multicentre retrospective study of children with psoriasis who received at least one injection of a biological agent, even off-licence, before the age of 12 years in France and Italy, collecting the data between April and August 2021. The data collected were from March 2012 up to August 2021. RESULTS: In total, 82 children (mean age: 9.1 years; females: 61.0%) received 106 treatments. The drugs administered were adalimumab (n = 49), etanercept (n = 37), ustekinumab (n = 15), anakinra (n = 2), infliximab (n = 2) and secukinumab (n = 1). The most common form of psoriasis was plaque psoriasis (62.9%). The Physician Global Assessment and the Psoriasis Area Severity Index (PASI) scores decreased significantly from baseline to 3 months after treatment initiation for the three main biological drugs; PASI went from 14.1 ± 9.4 to 4.1 ± 11.3 for adalimumab (p = 0.001), 14.9 ± 9.3 to 5.1 ± 4.0 for etanercept (p = 0.002) and 11.6 ± 8.3 to 2.6 ± 2.2 for ustekinumab (p = 0.007). A trend towards higher 2-year maintenance rates was observed for ustekinumab and adalimumab, compared with etanercept (p = 0.06). 52 children discontinued their biological therapy, most frequently due to inefficacy (n = 28) and remission (n = 14). Seven serious adverse events (SAEs) were reported, including four severe infections. DISCUSSION: Our analyses of drug survival and treatment patterns, combined with those of previous studies conducted in older children, indicate that there is a trend towards higher 2-year survival rates of ustekinumab and adalimumab. The SAEs identified were rare, but highlight the need for increased vigilance concerning infections. Overall, the biological therapies showed good effectiveness and safety profiles when used in daily practice for the treatment of young children with psoriasis.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Series of 49 French Pediatric Cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal adverse reaction. It can be difficult to diagnose, even more so among children, because symptoms may mimic other commonly encountered pediatric conditions. OBJECTIVE: To describe clinical and laboratory features of DRESS syndrome in the pediatric population (age ≤18 years) and establish causative agents and treatment modalities. METHODS: This was a multicenter retrospective study of probable and definite DRESS cases (Registry of Sever Cutaneous Adverse Reaction score ≥ 4) in children hospitalized in 15 French university hospitals between 2000 and 2020. RESULTS: We included 49 cases. All children had fever and rash, 69.4% had lymphadenopathy, and 65.3% had facial edema. The most common organ affected was the liver (83.7%). Treatment consisted of topical corticosteroid in only 30.6% and systemic corticosteroid in 55.1%; 12.2% received intravenous immunoglobulin. Among probable and likely culprit drugs, 65% were antibiotics and 27.5% were antiepileptics, median time to DRESS symptom onset after initiation of 15 days (13 days with antibiotics and 21 days with antiepileptics). Twenty-seven children had allergy assessment for causative agents, 65.4% of whom had positive tests. CONCLUSIONS: Culprit drugs are frequently antibiotics and antiepileptic drugs, and onset is often less than 2 weeks after treatment starts, especially with antibiotics. Treatment with topical corticosteroids appears to be sufficient in the least severe cases. Treatment by systemic corticosteroid therapy remains the reference treatment in case of severe organ damage.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Crusted scabies in children in France: a series of 20 cases.

To evaluate the risk factors for crusted scabies in children in France. The retrospective multicenter study, conducted in France, of children (aged < 18 years) with profuse and/or crusted scabies confirmed by dermoscopy and/or microscopy. Data were obtained using a standardized questionnaire. We included 20 children. The mean age was 4.5 years, and 70% of the patients were girls. Their medical history revealed a neurological pathology (agenesis of the corpus callosum; n = 1, 5.0%), prematurity (n = 1, 5.0%), Down syndrome (n = 1, 5.0%), atopic dermatitis (n = 2, 10%), and asthma (n = 2, 10.0%). Fifteen (75.0%) children were treated with steroids before being diagnosed with scabies: 12 (60.0%) with topical steroids, one (5.0%) with a systemic steroid, and two (10.0%) with inhaled steroids. One child (5.0%) lived in a precarious environment. The mean duration of pruritus was 3.4 months, and that of the skin lesions was 3.1 months. The most commonly affected areas for crusted scabies were the palms/hands (66.7%) and the armpits (33.3%). Thirteen children (65.0%) were hospitalized, 14 (70.0%) were treated with ivermectin and all received topical treatments; 85.7% were cured within an average of 38 days, but one child had a relapse 3 months later in the form of common scabies.Conclusion: The main risk factor for developing crusted scabies in France was the misdiagnosis and the use of corticosteroids, especially topical forms typically used in "healthy" children. Management of the children was effective and similar to that used in adults. What is Known: • Crusted scabies is an extremely contagious disease which is rarely reported in infancy, especially in healthy children. • The main risk factors include immunosuppression, physical debilitation, and intellectual disability. What is New: • The main risk factor of severe scabies in this study was delayed diagnosis associated with the use of topical or systemic corticosteroids. • The treatment was successful in 85.7% of cases, and 65% of children needed to be hospitalized.

Switching biologics in children with psoriasis: Results from the BiPe cohort.

BACKGROUND: There is currently little information on switching biologics in pediatric psoriasis. OBJECTIVE: To evaluate the real-world clinical practice and safety of switching biologics in the "Biological Treatments for Pediatric Psoriasis" (BiPe) cohort. METHODS: Data for all 134 patients included in the BiPe cohort were analyzed. A further evaluation of the subpopulation of patients who switched from a first-line biologic to a second-line biologic was then conducted. Drug survival rates were also compared between biologics given as first-line or second-line agents. RESULTS: Overall, 29 patients (female: 55%; mean age: 16.6 ± 3.0 years) switched between two biologics. Etanercept (ETN) was the first-line biologic used in 23 patients: 16 (69.6%) switched to adalimumab (ADA) and seven (30.4%) to ustekinumab (UST). Six patients received first-line ADA and switched to UST. Loss of efficacy (62.1%), primary inefficacy (20.7%), and parental choice (6.9%) were the main reasons for switching biologics. One (3.4%) of the switches was performed because of adverse events or intolerance. For UST and ADA, the 18-month drug survival rate did not differ according to whether the agent was given as a first-line or second-line biologic (UST: P = .24; ADA: P = .68). No significant differences in drug survival rates were observed between the three different switches (ADA to UST, ETN to ADA, and ETN to UST). CONCLUSION: Our study provided key insights into the real-life clinical practice of switching biologics in pediatric psoriasis patients. However, more information and guidance on switching biologics in pediatric psoriasis are needed to improve real-life practice and outcomes.

A Multicentre Randomised Controlled Study Evaluating the Effect of a Standardised Education Programme on Quality of Life, Disease Severity, and Disease Knowledge in Patients with Moderate-To-Severe Psoriasis: The EDUPSO Study.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease that has a profound effect on health-related quality of life (HRQoL). Patient education programmes may help patients to gain life-long control over their chronic disease. OBJECTIVE: This multicentre randomised controlled study evaluated whether a standardised multidisciplinary education programme was beneficial to psoriasis patients. METHODS: Adults with moderate-to-severe psoriasis were randomly assigned (1:1) to an intervention group to receive an educational programme or to a control group to receive usual care. Randomization was stratified by previous treatment history. The primary outcome was HRQoL, assessed by scoring the Skindex-29 domains emotion, symptom, and functioning. Psoriasis severity was assessed using the psoriasis area severity index (PASI). Levels of perceived stress, patient knowledge about psoriasis, and patient satisfaction were also assessed. Follow-up evaluations were performed at 3, 6, and 12 months. RESULTS: A total 142 patients formed the intention-to-treat population: 70 in the control group and 72 in the intervention group. Skindex component scores and the PASI were significantly lower at 3, 6, and 12 months as compared to baseline in both groups, but no significant differences were found between the groups. Knowledge about psoriasis improved significantly during follow-up amongst patients from the intervention group compared to controls (68% of correct answers vs. 56%; p < 0.01). Patient satisfaction with psoriasis management and treatment was also better in the intervention group. CONCLUSIONS: The standardised education programme did not improve HRQoL and disease severity in psoriasis, but led to a significant improvement in patient knowledge about the disease and increased patient satisfaction.

Sirolimus (Rapamycin) for Slow-Flow Malformations in Children: The Observational-Phase Randomized Clinical PERFORMUS Trial.

IMPORTANCE: Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. OBJECTIVE: To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. DESIGN, SETTING AND PARTICIPANTS: This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers. Statistical analysis was performed on an intent-to-treat basis from December 4, 2019, to November 10, 2020. INTERVENTIONS: Patients underwent an observational period, then switched to an interventional period when they received oral sirolimus (target serum levels, 4-12 ng/mL). The switch time was randomized from month 4 to month 8, and the whole study period lasted 12 months for each patient. MAIN OUTCOMES AND MEASURES: The primary outcome was change in the volume of vascular malformations detected on magnetic resonance imaging scan (with centralized interpretation) per unit of time (ie, between the interventional period and the observational period). Secondary outcomes included subjective end points: pain, bleeding, oozing, quality of life, and safety. RESULTS: Among the participants (35 girls [59.3%]; mean [SD] age, 11.6 [3.8] years), 22 (37.3%) had a pure venous malformation, 18 (30.5%) had a cystic lymphatic malformation, and 19 (32.2%) had a combined malformation, including syndromic forms. Variations in the volume of vascular malformations detected on magnetic resonance imaging scans associated with the duration period were not overall significantly different between the interventional period and the observational period (all vascular malformations: mean [SD] difference, -0.001 [0.007]; venous malformations: mean [SD] difference, 0.001 [0.004]; combined malformations: mean [SD] difference, 0.001 [0.009]). However, a significant decrease in volume was observed for children with pure lymphatic malformations (mean [SD] difference, -0.005 [0.005]). Overall, sirolimus had positive effects on pain, especially for combined malformations, and on bleeding, oozing, self-assessed efficacy, and quality of life. During sirolimus treatment, 56 patients experienced 231 adverse events (5 serious adverse events, none life-threatening). The most frequent adverse event was an oral ulcer (29 patients [49.2%]). CONCLUSIONS AND RELEVANCE: This observational-phase randomized clinical trial allows for clarifying the goals of patients and families when starting sirolimus therapy for children older than 6 years. Pure lymphatic malformations seem to be the best indication for sirolimus therapy because evidence of decreasing lymphatic malformation volume per unit of time, oozing, and bleeding and increasing quality of life was found. In combined malformations, sirolimus significantly reduced pain, oozing, and bleeding. Benefits seemed lower for pure venous malformations than for the 2 other subgroups, also based on symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02509468; clinicaltrialsregister.eu Identifier: 2015-001096-43.

Health care transition for patients with vascular malformations: a French multicenter cross-sectional study.

BACKGROUND: Health care transition (i.e., transition from pediatric to adult care) is challenging in chronic conditions but has been poorly studied in rare chronic skin diseases. We investigated the proportion of lost to follow-up among patients with superficial vascular malformations after health care transition. We also collected patients' opinions. This prospective, multicenter, cross-sectional study was performed at 7 French hospitals. We included patients aged 19-25 years, who were followed for a superficial vascular malformation before age 16, and who had completed the transition period in 2020. Data were collected from medical records and a questionnaire was sent to included patients asking about the health care transition. RESULTS: Among the 90 patients included, 41 (46%) were lost to follow-up after health care transition period. The age at diagnosis was significantly higher for lost to follow-up than non- lost to follow-up patients. The lost to follow-up proportion was similar between patients who changed and did not change hospitals during the transition. Responses to the questionnaire were obtained for 47 of 90 patients (52.2% response rate); most were satisfied with their care (n = 31/36, 86.1%); however, a lack of psychological support was reported. CONCLUSIONS: Health care transition is associated to a high rate of lost to follow-up. Early management seems associated to less lost to follow-up. Further studies are needed to better understand risk factors for a failed health care transition and its consequences.

Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial.

BACKGROUND: Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions in children and adults. They present as clusters of vesicles full of lymph and blood to various extents, inducing maceration, esthetic impairment, pain, and impaired quality of life. The treatment is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Topical sirolimus has recently been reported as effective in a few reports of patients with CMLMs. The objective is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults. METHODS: This French blinded multicenter within-person randomized controlled phase 2 trial aims to include 55 patients aged ≥ 6 years who have a primary CMLM. The CMLM will be divided into two equal areas that will be randomly allocated to 0.1% topical sirolimus or topical vehicle applied for 12 weeks. At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for eight more weeks. Patients will be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. The primary outcome will be improvement of the CMLM in the area treated with topical sirolimus compared to the area treated with topical vehicle by the investigator physician (blinded to the treatment) with the Physician Global Assessment score at week 12. Secondary outcomes will include: assessment of efficacy by independent experts on the basis of standardized photographs; impact on quality of life; efficacy for oozing, bleeding, erythema, and thickness evaluated by the investigators; and global efficacy as well as efficacy for functional and aesthetic impairment evaluated by the patient. Systemic passage of sirolimus will be measured at weeks 6, 12, and 20, and at week 16 for CMLMs ≥ 900 cm2. DISCUSSION: For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03972592. Registered on 3 June 2019. EU Clinical Trials Register EudraCT, 2018-001359-11.