Publications by authors named "Annabel Maruani"

124 Publications

A Blue-pigmented Lesion on the Cheek in a Three-year-old Girl: A Quiz.

Acta Derm Venereol 2021 Oct 28;101(10):adv00580. Epub 2021 Oct 28.

Department of Dermatology, Unit of Paediatric Dermatology, CHRU Tours, FR-37000 Tours.

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http://dx.doi.org/10.2340/actadv.v101.364DOI Listing
October 2021

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

JAMA Dermatol 2021 Nov;157(11):1289-1298

University of Tours, Centre Hospitalier Régional Universitaire Tours, Department of Pediatric Radiology, Tours, France.

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.
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http://dx.doi.org/10.1001/jamadermatol.2021.3459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444064PMC
November 2021

Cutaneous Horn on Four-year-old Child's Arm: A Quiz.

Acta Derm Venereol 2021 Oct 12;101(10):adv00567. Epub 2021 Oct 12.

Department of Dermatology, CHU Tours, FR-37000 Tours, France.

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http://dx.doi.org/10.2340/00015555-3902DOI Listing
October 2021

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

Orphanet J Rare Dis 2021 08 6;16(1):352. Epub 2021 Aug 6.

Department of Dermatology and Reference Center for Rare Diseases and Vascular Malformations (MAGEC), CHRU Tours, Avenue de La République, 37044, Tours Cedex 9, France.

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.
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http://dx.doi.org/10.1186/s13023-021-01970-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349005PMC
August 2021

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

J Allergy Clin Immunol Pract 2021 Jul 29. Epub 2021 Jul 29.

Service de Dermatologie, Hôtel Dieu, Centre Hospitalier Universitaire de Nantes, Nantes, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaip.2021.07.025DOI Listing
July 2021

Transient abdominal telangiectasia of the newborn.

Pediatr Dermatol 2021 Jul 21;38(4):864-867. Epub 2021 Jun 21.

Department of Dermatology, Nantes University, CHU Nantes, UMR 1280 PhAN, INRA, Nantes, France.

We report 20 newborns who developed, at a median age of 7 days, large abdominal patches of radially arranged purplish telangiectasia in a bilateral and symmetrical pattern in relation to the midline, creating a "butterfly wing" pattern. Clinical examination was normal in 13 newborns, six newborns had abdominal distention, and one newborn had poor weight gain due to inadequate breastfeeding. Most lesions spontaneously resolved within 3 months and did not reoccur for 19 newborns. Transient abdominal telangiectasia of the newborn (TATN) appears to be a distinctive entity that has not been previously described.
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http://dx.doi.org/10.1111/pde.14620DOI Listing
July 2021

Topical sirolimus 1% for benign lymphangiomatous papules after radiotherapy for endometrial and breast cancers: a report of three cases.

Eur J Dermatol 2021 Apr;31(2):252-254

Department of Dermatology and Reference Centre for Rare Diseases and Vascular Malformations (MAGEC), CHRU Tours, 37044 Tours Cedex 9, France, Universities of Tours and Nantes, INSERM 1246 - SPHERE, 37000 Tours, France.

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http://dx.doi.org/10.1684/ejd.2021.4000DOI Listing
April 2021

A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?

PLoS Negl Trop Dis 2021 03 17;15(3):e0009144. Epub 2021 Mar 17.

WorldWide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom.

Background: Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an individual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg.

Methodology/principal Findings: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported.

Conclusions/significance: Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance.
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http://dx.doi.org/10.1371/journal.pntd.0009144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968658PMC
March 2021

Primary lymphedema French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins).

Orphanet J Rare Dis 2021 01 6;16(1):18. Epub 2021 Jan 6.

Department of Dermatology and Reference Center for Rare Diseases and Vascular Malformations (MAGEC), CHRU Tours, 37044, Tours Cedex 9, France.

Primary lymphedema is a rare chronic pathology associated with constitutional abnormalities of the lymphatic system. The objective of this French National Diagnosis and Care Protocol (Protocole National de Diagnostic et de Soins; PNDS), based on a critical literature review and multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with primary lymphedema. This PNDS, written by consultants at the French National Referral Center for Primary Lymphedema, was published in 2019 ( https://has-sante.fr/upload/docs/application/pdf/2019-02/pnds_lymphoedeme_primaire_final_has.pdf ). Primary lymphedema can be isolated or syndromic (whose manifestations are more complex with a group of symptoms) and mainly affects the lower limbs, or, much more rarely, upper limbs or external genitalia. Women are more frequently affected than men, preferentially young. The diagnosis is clinical, associating mild or non-pitting edema and skin thickening, as confirmed by the Stemmer's sign (impossibility to pinch the skin on the dorsal side or the base of the second toe), which is pathognomonic of lymphedema. Limb lymphoscintigraphy is useful to confirm the diagnosis. Other causes of swelling or edema of the lower limbs must be ruled out, such as lipedema. The main acute lymphedema complication is cellulitis (erysipelas). Functional and psychological repercussions can be major, deteriorating the patient's quality of life. Treatment aims to prevent those complications, reduce the volume with low-stretch bandages, then stabilize it over the long term by exercises and wearing a compression garment. Patient education (or parents of a child) is essential to improve observance.
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http://dx.doi.org/10.1186/s13023-020-01652-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789008PMC
January 2021

Vesiculopustular Eruption in a Newborn with Down's Syndrome: A Quiz.

Acta Derm Venereol 2021 Feb 16;101(2):adv00394. Epub 2021 Feb 16.

INSERM 1246-SPHERE, University of Tours, University of Nantes, FR-37000 Tours, France.

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http://dx.doi.org/10.2340/00015555-3731DOI Listing
February 2021

Faecal calprotectin in hidradenitis suppurativa: a study of 55 patients.

Eur J Dermatol 2020 Aug;30(4):422-424

Universities of Tours and Nantes, INSERM 1246 - SPHERE, 37000 Tours, France, CHRU Tours, Department of Dermatology, Hospital Trousseau, 37044, Tours CEDEX 9, France.

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http://dx.doi.org/10.1684/ejd.2020.3813DOI Listing
August 2020

Multiple Erosions and Crusts on Legs in a Returning Traveller: A Quiz.

Acta Derm Venereol 2020 08 25;100(15):adv00253. Epub 2020 Aug 25.

Department of Dermatology, University Hospital Center of Tours, 37044 Tours Ceddex 9, France.

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http://dx.doi.org/10.2340/00015555-3604DOI Listing
August 2020

"Laser tag purpura": a new form of exercise-induced purpura.

Eur J Dermatol 2020 Aug;30(4):418-420

Department of Dermatology, CHRU Tours and University of Tours, Tours, France.

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http://dx.doi.org/10.1684/ejd.2020.3817DOI Listing
August 2020

Long-term follow-up of intracranial arteriovenous malformations with frontal capillary malformation (Wyburn-Mason syndrome or Bonnet-Dechaume-Blanc syndrome): three case reports.

Int J Dermatol 2020 Aug 19;59(8):e276-e278. Epub 2020 May 19.

Reference Center for Rare Diseases and Vascular Malformations (MAGEC), CHRU Tours, Tours Cedex 9, France.

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http://dx.doi.org/10.1111/ijd.14947DOI Listing
August 2020

Research Techniques Made Simple: Randomized Controlled Trials for Topical Drugs in Dermatology: When and How Should We Use a Within-Person Design?

J Invest Dermatol 2020 05;140(5):931-938.e1

University of Tours and University of Nantes, INSERM, SPHERE 1246, Tours, France; INSERM CIC 1415, CHRU Tours, Tours, France.

Topical drugs are often used as first-line treatment for dermatological conditions. Depending on the disease and the drug, three main designs can be used for randomized controlled trials assessing topical drugs: the classical individual parallel design, the cluster randomized design, and designs allowing within-individual comparisons, including the cross-over design (in which patients are randomized to a sequence of interventions) and the within-person design (also called the split-body design). Within-person design can be used to compare different drugs concomitantly in the same patient. Randomization does not concern patients but rather lesions or body sites within patients, and the drugs to be compared are applied to the different lesions (or sites). This design considerably reduces interobservation variability, and thus, the number of patients to be included in the trial (sample size). However, this design has major methodological constraints, especially the need to resolve the problem of a possible carry-across effect. First, we describe the specificities of randomized controlled trials evaluating a topical drug. Second, we present the different designs available and discuss the methodological points that should be considered, especially for a within-person design. Finally, we compare the relevance of the within-person design with that of other trial designs by considering three different scenarios.
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http://dx.doi.org/10.1016/j.jid.2020.03.945DOI Listing
May 2020

Sport activities and exercise in individuals with lymphedema: a French national survey on practices and fears.

Eur J Dermatol 2020 Feb;30(1):63-66

Department of Dermatology and Reference Center for Rare Diseases and Vascular Malformations (MAGEC), CHRU Tours, 37044 Tours Cedex 9, France, Universities of Tours and Nantes, INSERM 1246 - SPHERE, 37000 Tours, France.

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http://dx.doi.org/10.1684/ejd.2020.3705DOI Listing
February 2020

High-Frequency Transient Elastography Prototype to Assess Skin (Dermis) Fibrosis: A Diagnostic Study in Patients with Venous Insufficiency and Controls.

Ultraschall Med 2021 Oct 18;42(5):503-513. Epub 2020 Mar 18.

UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.

Purpose:  High-frequency transient elastography (HF-TE) is a noninvasive technique for assessing shear-wave speed and finally elasticity in thin tissue such as the skin. It has never been validated for monitoring fibrotic skin diseases. The purpose was to evaluate the potential of HF-TE to assess skin fibrosis in patients with chronic venous disorders (CVD).

Materials And Methods:  This clinical study enrolled 48 patients at various stages of CVD and 48 paired healthy volunteers. Subjects underwent a clinical examination with an evaluation of Rodnan's fibrosis skin score. We studied the dermis thickness measured using ultrasound (US) and elasticity measurements using cutometer and HF-TE studied according to 3 cutaneous zones positioned on the leg. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnosis performance for a combined parameter (PRL) based on a logistic regression model using both elasticity and dermal thickness.

Results:  Patients with CVD had significantly higher values of skin elasticity than healthy subjects, 134.5 kPa and 132.1 kPa vs. 91.3 kPa, respectively. The dermis thickness also increased with escalation in CVD stage for all studied zones. The PRL parameter had an AUC value of 0.79 for all zones and stages of CVD clustered. The discriminating power of PRL increased with escalation of the CVD stage; with an AUC value of up to 0.89 for evolved stages, and a sensitivity and specificity of 0.79 and 0.89, respectively.

Conclusion:  HF-TE, coupled with a US measurement of dermis thickness, made it possible to propose a new biomarker, which proved to be a good diagnostic tool for skin fibrosis.
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http://dx.doi.org/10.1055/a-1047-3146DOI Listing
October 2021

Short-term Effect and Acceptability of Manual Lymphatic Drainage for Paediatric Limb Lymphoedema: A Prospective Study.

Acta Derm Venereol 2020 Apr 29;100(8):adv00125. Epub 2020 Apr 29.

Paediatric lymphoedema (LE) is a rare condition, for which there is little data available regarding treatments. The aim of this study was to assess the short-term effect and acceptability of a 30-min session of manual lymphatic drainage (MLD) in children with well-documented LE of the lower limbs. Fifteen children were included (8 males; median age 11 years). Comparison of the sum of circumference values for the whole limb before and after MLD revealed a slight, but significant, reduction (from a median of 289.8 to 285.5 cm, p = 0.024), but the limb volumes did not decrease significantly (from a median of 4,870.3 to 4,772.3 ml, p = 0.394). Dermal thickness, measured by high-resolution ultrasound, decreased from 1.44 to 1.40 mm (p < 0.001). All children reported improvement in well-being, and found MLD useful. In conclusion, MLD is well accepted by children, but has poor impact on LE swelling. However, it decreases cutaneous oedema by mobilizing the lymph fluid.
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http://dx.doi.org/10.2340/00015555-3447DOI Listing
April 2020

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.

Trials 2019 Dec 17;20(1):739. Epub 2019 Dec 17.

INSERM U1246 -SPHERE « MethodS in Patients-centered outcomes and HEalth REsearch », University of Nantes, University of Tours, 37000, Tours, France.

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 cm.

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.
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http://dx.doi.org/10.1186/s13063-019-3767-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918625PMC
December 2019

Reverse Phenotyping in Patients with Skin Capillary Malformations and Mosaic GNAQ or GNA11 Mutations Defines a Clinical Spectrum with Genotype-Phenotype Correlation.

J Invest Dermatol 2020 05 11;140(5):1106-1110.e2. Epub 2019 Nov 11.

Dermatology Department, Dijon Burgundy University Hospital, Dijon, France; INSERM UMR1231, Team Genetics of Development Anomalies, Bourgogne-Franche-Comté University, Dijon, France; Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC)-Mosaic, Burgundy University Hospital, Dijon, France.

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http://dx.doi.org/10.1016/j.jid.2019.08.455DOI Listing
May 2020

Efficacy and Tolerance of Sirolimus (Rapamycin) for Extracranial Arteriovenous Malformations in Children and Adults.

Acta Derm Venereol 2019 Nov;99(12):1105-1109

University of Tours, CHRU Tours, FR-37044 Tours, France.

Managing extracranial arteriovenous malformations is challenging. Sirolimus (rapamycin) is increasingly being used when surgery and embolization are not advised. Because of its anti-angiogenic properties here we report all extracranial arteriovenous malformation cases treated with sirolimus in 2 French tertiary centers for vascular anomalies. The outcomes were efficacy (complete, partial, no response) based on arteriovenous malformation volume and necrosis/hemorrhage and side effects. We retrospectively included 10 patients (7 children). The sirolimus dose ranged from 0.6 to 3.5 mg/m2. Median (interquartile range [IQR]) treatment time was 24.5 (4.5; 35) months. Five patients showed no response and 5 showed partial response at a median (IQR) of 3 (1; 5) months followed in 2 cases by therapeutic resistance (i.e., progressive disease after 9 and 24 months of treatment). The most frequent side effect was mouth ulcers. This study shows poor efficacy of sirolimus for treating extracranial arteriovenous malformations.
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http://dx.doi.org/10.2340/00015555-3273DOI Listing
November 2019

Yellowish Nodules on the Vulva in a 6-year-old Girl: A Quiz.

Acta Derm Venereol 2019 Jul;99(9):837-838

Department of Dermatology, CHR Orléans, FR-45650 Orléans, France.

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http://dx.doi.org/10.2340/00015555-3204DOI Listing
July 2019

[Superficial angiomas: Treatment].

Presse Med 2019 Apr 19;48(4):388-397. Epub 2019 Apr 19.

Université François-Rabelais de Tours, centre hospitalier régional universitaire de Tours, service de neuroradiologie interventionnelle, 37000 Tours, France; Centre hospitalier régional universitaire de Tours, centre de référence des maladies rares de la peau et des muqueuses d'origine génétique (MAGEC), 37000 Tours, France.

Beta-blockers are efficient for treating complicated infantile hemangiomas; propranolol is currently the first-line treatment. Superficial vascular malformations have to be managed by multidisciplinary teams. T2 FAT-SAT MRI is the most interesting sequence to explore superficial vascular malformations. Recent advances in molecular biology allow exploring new genetic mutations which could be involved in vascular malformations and be the target of new drugs. Mammalian target of rapamycin (mTOR) inhibitors are promising drugs for slow-flow malformations. Arteriovenous malformations are aggressive lesions with very few treatment options.
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http://dx.doi.org/10.1016/j.lpm.2019.03.010DOI Listing
April 2019

Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): protocol for a randomised controlled trial.

BMJ Open 2019 04 20;9(4):e024974. Epub 2019 Apr 20.

Department of Dermatology, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory disease affecting 10%-15% of children in Europe. There is a need for new primary preventive therapeutic strategies in at-risk populations. Recent research has indicated that atopic diseases are associated with a disrupted gut microbial 'balance' in early life raising the possibility that interventions which yield optimal patterns of microflora could improve host's health. Prebiotics, sugars with immunomodulatory properties that stimulate the diversity of the digestive microbiota, are ideal candidates for such research. So far, most clinical trials have focused on improving infant gut colonisation postnatally. However, prenatal life is a crucial period during which different tolerance mechanisms are put in place. We aim to determine whether antenatal prebiotics supplementation prevents AD in high-risk children.

Methods And Analysis: This is a randomised, multicentre, double-blind, trial to evaluate the effectiveness of antenatal prebiotic maternal supplementation (galacto-oligosaccharide/inulin) in pregnant women versus placebo on the occurrence of AD at 1 year of age in at-risk children (defined as having a maternal history of atopic disease). Participating women will be randomised to daily ingestion of a prebiotics or placebo (maltodextrin) from 20 weeks' gestation until delivery. The primary outcome is the prevalence of AD at 1 year of age, using the version of the UK Working Party Diagnostic Criteria optimised for preventive studies. Key secondary endpoints are AD severity, quality of life and prebiotics tolerance. The target sample size is 376 women (188 patients per group) which will provide 80% power to detect a 33% reduction of the risk of AD in the verum group (α=0.05). The primary analysis will be based on the intention-to-treat principle.

Ethics And Dissemination: Results will be presented in peer-reviewed journals and at international conferences. Ethics approval for the study was obtained from the institutional ethical review board of 'Comité de Protection des Personnes Sud Ouest-Outre-Mer III' of the University Hospital Centre of Bordeaux (2017/13).

Trial Registration Number: NCT03183440; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-024974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500253PMC
April 2019

Non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.

Cochrane Database Syst Rev 2019 04 8;4:CD011541. Epub 2019 Apr 8.

Department of Dermatology, Université François-Rabelais de Tours, Tours, France, 37044.

Background: Guttate psoriasis displays distinctive epidemiological and clinical features, making it a separate entity within the heterogeneous group of cutaneous psoriasis types. It is associated with genetic, immune, and environmental factors (such as stress and infections) and usually arises in younger age groups (including children, teenagers, and young adults). There is currently no cure for psoriasis, but various treatments can help to relieve the symptoms and signs. The objectives of treatment when managing an acute flare of guttate psoriasis are to reduce time to clearance and induction of long-term remission after resolution. This is an update of a Cochrane Review first published in 2000; since then, new treatments have expanded the therapeutic spectrum of systemic treatments used for psoriasis.

Objectives: To assess the effects of non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.

Search Methods: We searched the following databases up to June 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials. We checked the proceedings of key dermatology conferences from 2004 to 2018, and also searched for trials in the US Food and Drug Administration (FDA) database for drug registration.

Selection Criteria: All randomised controlled trials assessing the effects of treatments for acute guttate psoriasis or an acute guttate flare of chronic psoriasis clinically diagnosed in children and adults. This included all topical and systemic drugs, biological therapy, phototherapy (all forms: topical and systemic), and complementary and alternative therapies. We compared these treatments against placebo or against another treatment. We did not include studies on drugs that aim to eradicate streptococcal infection. We did not include studies when separate results for guttate psoriasis participants were not available.

Data Collection And Analysis: Two review authors independently assessed study eligibility and methodological quality and extracted data. We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'percentage of participants clear or almost clear (i.e. obtaining Psoriasis Area Severity Index (PASI) 100/90 and/or Physician's Global Assessment (PGA) of 0 or 1)' and 'percentage of participants with adverse effects and severe adverse effects'. Our secondary outcomes were 'number of relapses of guttate psoriasis or flares within a period of six months after the treatment has finished', 'percentage of participants achieving a PASI 75 or PGA of 1 or 2', and 'improvement in participant satisfaction measures and quality of life assessment measures'. We used GRADE to assess the quality of the evidence for each outcome.

Main Results: This review included only one trial (21 participants), which compared fish oil-derived (n-3) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (10 participants) to soya oil-derived (n-6) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (11 participants) administered intravenously twice daily for 10 days, with a total follow-up of 40 days. The study was conducted in a single centre in Germany in 18 men and three women, aged between 21 and 65 years, who were in hospital with acute guttate psoriasis and had mean total body surface involvement of 25.7% ± 20.4% (range 10 to 90). The study was funded by a company that produces the oil emulsions. We found no other evidence regarding non-antistreptococcal interventions used in clinical practice for guttate psoriasis, such as topical treatments (corticosteroids, vitamin D₃ analogues), systemic drugs, biological therapy, and phototherapy.The primary outcomes of the review were not measured, and only one of our secondary outcomes was measured: improvement in participant satisfaction measures and quality of life assessment measures. However, the study authors did report that there was rare skin irritation at the site of peripheral intravenous route, but the number of affected participants was not provided.Improvement between baseline and day 10, using a non-validated score assessed by participants themselves daily based on five items (appearance of lesions, impairment of daily life, pruritus, burning, and pain), was greater in the group that received the fish oil-derived (n-3) fatty acid-based lipid emulsion (75%) than in the group receiving the soya oil-derived (n-6) fatty acid-based lipid emulsion (18%) (one trial, 21 participants). However, these results are uncertain as they are based on very low-quality evidence.

Authors' Conclusions: There is no evidence regarding topical and systemic drugs, biotherapy, or phototherapy in guttate psoriasis (we did not consider drugs that aimed to eradicate streptococcal infection because these are assessed in another Cochrane Review). We are uncertain of the effect of intravenously administered lipid emulsion on guttate psoriasis because the quality of the evidence is very low, due to risk of bias (unclear risk of bias for all domains), indirectness (the trial only included adults, and the follow-up from baseline was only 10 days), and imprecision (small number of participants).This review highlights the need for trials assessing the efficacy and safety of phototherapy and topical and systemic drugs for guttate psoriasis. There is also a need for studies that clearly distinguish the specific population with guttate psoriasis from the larger group of people with chronic plaque psoriasis, and children and young adults should be assessed as a distinct group.
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http://dx.doi.org/10.1002/14651858.CD011541.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452774PMC
April 2019

A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial.

Trials 2019 Mar 25;20(1):184. Epub 2019 Mar 25.

Univ Rennes, Rennes, France.

Background: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates.

Methods: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter.

Discussion: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health.

Trial Registration: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.
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http://dx.doi.org/10.1186/s13063-019-3276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434814PMC
March 2019
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