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1.
Am J Gastroenterol ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382676

RESUMO

Drug-induced acne is a common side effect to a wide array of pharmacological therapies and is characterized by a monomorphic, papulopustular eruption typically affecting the face, scalp, and the upper thorax. Corticosteroids and Janus kinase inhibitors (JAKi) are commonly used for the treatment of inflammatory bowel disease (IBD) and are known to aggravate a prior tendency to acne or trigger the development of new acneiform eruptions. Recent attention on managing drug-induced acne has been driven by the increasing use of JAKi, an expanding therapeutic class in IBD and several other immune-mediated inflammatory diseases. Both randomized controlled trials and real-world studies have identified acne as one of the most common treatment-emergent adverse events in JAKi. Left untreated, this common skin reaction can significantly impact patient self-esteem and quality of life leading to poor treatment adherence and suboptimal IBD control. This review examines the characteristics of drug-induced acne in IBD treatments, provides a practical guide for gastroenterologists to manage mild to moderate occurrences, and highlights when to seek specialist dermatology advice. Such approaches enable early treatment of a common and often distressing adverse event and optimizes the management of IBD by preventing the premature discontinuation or dose reduction of efficacious IBD drugs.

3.
Br J Dermatol ; 191(2): 177-186, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38863109

RESUMO

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.


Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing disease that affects 7­15% of children worldwide. Therapeutic patient education (TPE) is recommended for children with AD, but no agreement has been reached on the best way to tailor delivery. While repeated multidisciplinary group education sessions in a hospital setting have been found effective, this type of intervention requires a lot of resources and is time-consuming. To assess the benefits of TPE in children with AD, researchers in France carried out this study with children with moderate-to-severe AD, to compare a 1-hour nurse-led education session in addition to standard care vs. standard care alone. The main aim of this research was to assess the effectiveness of a TPE intervention over a period of 6 months, using a measurement tool called the SCORAD (SCORing of Atopic Dermatitis index). We found no additional benefits in terms of long-term severity control and quality of life at 6 months of a 1-hour nurse-led education intervention in children with AD treated with standard care. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for people in the moderate AD subgroup.


Assuntos
Dermatite Atópica , Educação de Pacientes como Assunto , Humanos , Dermatite Atópica/terapia , Dermatite Atópica/enfermagem , Masculino , Feminino , Pré-Escolar , Criança , Resultado do Tratamento , Qualidade de Vida , Pais/educação , Lactente
4.
Acta Derm Venereol ; 104: adv10321, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738770

RESUMO

Atopic dermatitis (AD) is one of the most common inflammatory diseases, and has a higher prevalence among females in adulthood. The aim of this observational, cross-sectional, survey-based study was to evaluate the impact of AD on the daily lives of adult women patients. A scientific committee composed exclusively of women constructed a specific questionnaire in partnership with the French Eczema Association. Severity of AD was evaluated with the Patient-Oriented Eczema Measure (POEM). A sample of 1,009 adult women (mean age ± standard deviation: 41.8 ± 14.2 years) with AD was identified from a representative sample of the French population (82% response rate 1,230 women surveyed). According to the POEM, 50.64% (n = 511) of subjects were identified as having mild AD, 39.35% (n = 397) moderate AD, and 10.01% (n = 101) severe AD. Overall, 67.7% (n = 682) reported that their eczema involved a visible area (face, neck or hands), and 19.6% (n = 198) a sensual area (breasts/chest, genital area or buttocks). Of the 720 women with menstrual cycles, exacerbations of AD were reported to occur mostly before (50.6%) and during (48.3%) menstruation. A small proportion of women, 7.3% (n = 74), reported being afraid of  becoming pregnant because of their eczema. If AD involvement was in a visible area it had a greater impact on romantic relationships, sexual relationships and occupation. If AD involvement was in a sensual area it had a greater influence on romantic relationships and sexuality. Particular attention should be given to patients with localization of AD on the face, neck or hands, as they have a higher risk of social exclusion. Moreover, these results should encourage health professionals to ask patients with AD about the possible involvement of sensual areas.


Assuntos
Dermatite Atópica , Qualidade de Vida , Índice de Gravidade de Doença , Humanos , Feminino , Dermatite Atópica/psicologia , Dermatite Atópica/epidemiologia , Dermatite Atópica/diagnóstico , Adulto , Estudos Transversais , França/epidemiologia , Pessoa de Meia-Idade , Efeitos Psicossociais da Doença , Adulto Jovem , Inquéritos e Questionários , Inquéritos Epidemiológicos , Gravidez
5.
BMJ Open ; 14(5): e085969, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821568

RESUMO

INTRODUCTION: Chronic wound care remains a critical public health challenge in terms of prevalence, quality of life and healthcare costs on a global scale. Currently used methods to assess the size and content of wounds include direct contact techniques based on double-layer film, ruler measurements, digital photography and visual examination. Nowadays, despite these evaluations, close monitoring and tracking of these chronic wounds remain a great challenge. The use of telemonitoring through digital measurement tools may offer a potential means of improving healing management processes. Many studies have evaluated the size and content of the wound through digital devices such as mobile phones and computers. However, the clinical accuracy of these tools remains to be clarified. The objective of this systematic review is to assess and consolidate the current state-of-the-art digital devices for both quantitative (length, width, surface area, perimeter, volume and depth) and qualitative (granulation, fibrin, necrosis and slough) indicators of wound care. METHODS AND ANALYSIS: We will include studies using digital measurement methods from databases such as EBSCO, Cochrane Library, MEDLINE, Web of Science and EMBASE, limited to French and English publications until November 15, 2023. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, selection involves two independent reviewers conducting title and abstract screenings, study selections, data extractions and risk-of-bias assessments using QUADAS-2. Discrepancies will be resolved through discussion or a third reviewer. ETHICS AND DISSEMINATION: Primary data will not be collected in this study; thus, ethical approval will not be required. The study's findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023396642.


Assuntos
Revisões Sistemáticas como Assunto , Cicatrização , Humanos , Projetos de Pesquisa , Fotografação , Ferimentos e Lesões/terapia
6.
N Engl J Med ; 390(14): 1339-1341, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38598804
7.
J Eur Acad Dermatol Venereol ; 38(9): 1818-1827, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38595321

RESUMO

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. OBJECTIVES: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. METHODS: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). CONCLUSIONS AND RELEVANCE: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.


Assuntos
Síndrome de Costello , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Síndrome de Costello/genética , Síndrome de Costello/complicações , Estudos Prospectivos , Feminino , Masculino , Criança , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Pré-Escolar , Adulto , Adulto Jovem , Displasia Ectodérmica/genética , Síndrome de Noonan/genética , Síndrome de Noonan/complicações , Acantose Nigricans/genética , Diagnóstico Diferencial , Ceratodermia Palmar e Plantar/genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/complicações , Fenótipo , Papiloma/genética , Papiloma/patologia , Acitretina/uso terapêutico , Sobrancelhas/anormalidades , Sobrancelhas/patologia , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/etiologia , Lactente , Ceratolíticos/uso terapêutico , Fácies
8.
Clin Genet ; 104(5): 554-563, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37580112

RESUMO

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.


Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Mutação , Detecção Precoce de Câncer , Transtornos do Crescimento/diagnóstico , Tumor de Wilms/diagnóstico , Tumor de Wilms/epidemiologia , Tumor de Wilms/genética , Classe I de Fosfatidilinositol 3-Quinases/genética
9.
Pediatr Dermatol ; 40(5): 835-840, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37442765

RESUMO

BACKGROUND: Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. METHODS: Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. RESULTS: Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001). CONCLUSIONS: This study demonstrated the treatment-resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Masculino , Criança , Feminino , Adalimumab/uso terapêutico , Psoríase/tratamento farmacológico , Etanercepte/uso terapêutico , Ustekinumab/uso terapêutico , Terapia Biológica , Resultado do Tratamento , Produtos Biológicos/uso terapêutico , Índice de Gravidade de Doença
12.
Adv Ther ; 39(11): 5203-5215, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36112312

RESUMO

INTRODUCTION: Despite the existence of multiple assessment scores for psoriasis severity, skin disease with limited skin lesions but significant impairment of quality of life can be difficult to classify, leading to under- or overtreatment. Our objective was to obtain consensus on clinical criteria to classify psoriasis severity in French clinical practice, with a focus on moderate disease, using a modified Delphi method. METHODS: A steering committee (SC) formulated a 22-item questionnaire to classify moderate psoriasis. An independent panel of French dermatologists indicated their level of agreement for each item using a 9-point Likert scale (round 1). Items without a strong consensus were modified and included in round 2. For each item, strong consensus was defined as at least 75% of scores ≥ 7 and median score ≥ 8; good consensus was defined as at least 75% of scores ≥ 7 or median score ≥ 8. RESULTS: Of 80 dermatologists who agreed to participate, 47 (59%) responded in round 1. All participants from round 1 responded in round 2. Fifteen (68%) items achieved strong consensus and four (18%) achieved good consensus. For psoriasis severity, several clinical dimensions assessed both by the physician (location, symptoms, temporality, previous treatments) and the patient (perception, physical and psychological impairment) obtained consensus. The following were considered sufficient to confirm that psoriasis is at least at a moderate stage: limited involvement but with an impact on patient/family quality of life; involvement of a special area; presence of uncontrolled symptoms (scaling, bleeding, pruritus, insomnia); accumulation of mild intensity symptoms; presence of burdensome onychodystrophy; failure of well-applied topical treatments. There was strong consensus that recognition of moderate psoriasis should lead to reassessment of topical treatments. CONCLUSION: Our modified Delphi panel suggests detailed criteria to help physicians classify patients with psoriasis which is at least at a moderate stage, which could, in turn, improve treatment in these patients.


Assuntos
Psoríase , Qualidade de Vida , Consenso , Técnica Delphi , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença
13.
Am J Med Genet A ; 188(11): 3343-3349, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35972031

RESUMO

Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.


Assuntos
Cútis Laxa , Cálcio , Doenças das Cartilagens , Cútis Laxa/genética , DNA Complementar , Fator de Crescimento Epidérmico , Feminino , Gastroenteropatias , Humanos , Lactente , Proteínas de Ligação a TGF-beta Latente/genética , RNA , Doenças Respiratórias , Fator de Crescimento Transformador beta , Doenças Urológicas
14.
Paediatr Drugs ; 24(3): 281-292, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35397731

RESUMO

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.


Assuntos
Psoríase , Ustekinumab , Adalimumab/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Etanercepte , Feminino , Humanos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversos
16.
Pediatr Dermatol ; 39(1): 35-41, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34888920

RESUMO

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.


Assuntos
Produtos Biológicos , Psoríase , Adalimumab/efeitos adversos , Adolescente , Adulto , Produtos Biológicos/efeitos adversos , Criança , Etanercepte/efeitos adversos , Feminino , Humanos , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Ustekinumab/uso terapêutico , Adulto Jovem
17.
Hum Mol Genet ; 31(7): 1105-1114, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-34686882

RESUMO

Functional skin barrier requires sphingolipid homeostasis; 3-ketodihydrosphingosine reductase or KDSR is a key enzyme of sphingolipid anabolism catalyzing the reduction of 3-ketodihydrosphingosine to sphinganine. Biallelic mutations in the KDSR gene may cause erythrokeratoderma variabilis et progressive-4, later specified as PERIOPTER syndrome, emphasizing a characteristic periorifical and ptychotropic erythrokeratoderma. We report another patient with compound heterozygous mutations in KDSR, born with generalized harlequin ichthyosis, which progressed into palmoplantar keratoderma. To determine whether patient-associated KDSR mutations lead to KDSR substrate accumulation and/or unrecognized sphingolipid downstream products in stratum corneum (SC), we analyzed lipids of this and previously published patients with non-identical biallelic mutations in KDSR. In SC of both patients, we identified 'hitherto' unobserved skin ceramides with an unusual keto-type sphingoid base in lesional and non-lesional areas, which accounted for up to 10% of the measured ceramide species. Furthermore, an overall shorter mean chain length of free and bound sphingoid bases was observed-shorter mean chain length of free sphingoid bases was also observed in lesional psoriasis vulgaris SC, but not generally in lesional atopic dermatitis SC. Formation of keto-type ceramides is probably due to a bottle neck in metabolic flux through KDSR and a bypass by ceramide synthases, which highlights the importance of tight intermediate regulation during sphingolipid anabolism and reveals substrate deprivation as potential therapy.


Assuntos
Dermatite Atópica , Ictiose , Ceratodermia Palmar e Plantar , Oxirredutases/metabolismo , Ceramidas/metabolismo , Epiderme/metabolismo , Humanos , Ceratodermia Palmar e Plantar/genética , Mutação , Esfingolipídeos/genética , Esfingolipídeos/metabolismo
18.
JAMA Dermatol ; 157(11): 1289-1298, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524406

RESUMO

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.


Assuntos
Anormalidades Linfáticas , Malformações Vasculares , Adolescente , Criança , Feminino , Humanos , Anormalidades Linfáticas/tratamento farmacológico , Qualidade de Vida , Sirolimo/efeitos adversos , Resultado do Tratamento , Malformações Vasculares/complicações , Malformações Vasculares/tratamento farmacológico
19.
Ann Biol Clin (Paris) ; 79(3): 233-240, 2021 Jun 01.
Artigo em Francês | MEDLINE | ID: mdl-34165432

RESUMO

The Sezary syndrome has been defined by a triad combining erythrodermia, generalized lymphadenopathy, and the presence of circulating Sezary cells > 1 × 109/L characterized by a CD4+/CD8- phenotype with loss of one or more T antigens (mainly CD7 and/or CD26). We retrospectively reviewed the immunophenotypic profiles of 10 SS patients followed in our institution (University Hospital at Nancy, France). The application of the WHO criteria resulted in a diagnostic confirmation for 9 out of 10 cases. Since 2008, new diagnostic and staging criteria have been proposed, including the CD158k/KIR3DL2 receptor detection. The application of these new criteria to our cohort led us to notice a phenotypic heterogeneity of our cases but allowed to achieve a relevant diagnosis of Sezary syndrome in all cases, especially for patients with lymphopenia. The use of such a panel of monoclonal antibodies also optimized the follow-up of the patients.


Assuntos
Dipeptidil Peptidase 4 , Neoplasias Cutâneas , Antígenos CD , Biomarcadores Tumorais , Linfócitos T CD8-Positivos , Citometria de Fluxo , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico
20.
Arch Pediatr ; 28(5): 417-421, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33994265

RESUMO

BACKGROUND: Children with skin disorders usually receive care from a pediatrician, despite their limited training in this discipline. The advice of a dermatologist is frequently requested. OBJECTIVES: To estimate the degree of concordance in the diagnosis, treatment, advice, and recommended follow-up of skin disorders between pediatricians (in private practice or a pediatric emergency department [PED]) and a dermatologist. METHODS: This prospective study was carried out between June 25 and September 13, 2018. All patients younger than 18 years consulting at the PED of the University Children's Hospital or a pediatric private practice in Nancy, France, for a dermatological disorder (primary complaint) were included. Photographs, medical data, diagnosis, treatment, advice and follow-up recommended by the pediatricians were recorded in a dedicated anonymous medical file. Clinical data and photographs were subsequently reviewed by a dermatologist who provided a diagnosis. RESULTS: A total of 103 patients were included and 99 were analyzed: 53 from the PED and 46 from private practice (three patients were excluded because of unclear photographs and one was referred for maxillofacial advice). The median age was 4 years and there was a slight predominance of females (53.5%). The seven main diagnoses were: atopic dermatitis, insect bites, nonspecific viral rash, viral urticaria, hand-foot-and-mouth disease, impetigo, and contact dermatitis. The rate of agreement between the pediatricians and the dermatologist was 55% for diagnosis (73% for atopic dermatitis, 53% for insect bites, 33% for nonspecific viral rash), 40% for treatment, 54% for advice, and 58% for recommended follow-up. Reinterpretation by the dermatologist changed patient management in 15% of cases. CONCLUSIONS: The significant discordance between the pediatricians and the dermatologist suggests the need for a greater emphasis on dermatological disorders in medical training programs and for closer collaboration between disciplines for the benefit of younger patients.


Assuntos
Dermatologia/métodos , Dermatopatias/terapia , Adolescente , Criança , Pré-Escolar , Dermatologia/normas , Feminino , França , Humanos , Lactente , Masculino , Pediatria/métodos , Estudos Prospectivos , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos
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