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4.
Genet Med ; 21(9): 2025-2035, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30723320

RESUMO

PURPOSE: Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. METHODS: Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. RESULTS: We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. CONCLUSION: In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.

7.
Int Wound J ; 15(4): 508-518, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29767853

RESUMO

Nicorandil-induced ulcers remain often poorly recognised, with a late diagnosis and an inadequate management. We aimed to provide a clinical overview of the 148 spontaneously reported cases of nicorandil-induced ulcers to the French pharmacovigilance network between 2005 and 2014 and to complete this picture with worldwide published cases over the same period. Spontaneously reported nicorandil-induced ulcers were mainly mucosal (oral and anal) with a previous trauma in 23·0% of patients, revealed by a severe complication in 12·8% of cases. The mean cumulative dose of nicorandil was higher in serious cases. The median delay between the start of nicorandil use and the onset of the ulcer was 23·4 months, and after the ulcer was diagnosed, the median time to incriminate nicorandil was still 3·3 months, being shorter for mucosal ulcerations than for cutaneous ulcerations (5·2 versus 14·0 months, P = 0·001). The anatomic distribution in the 199 published cases differed slightly, but delays were similar. The hypothesis of mechanism becomes more precise, leaving no doubt about the necessity to discontinue the treatment. Practitioners need to be aware that nicorandil-induced ulcers can occur in many locations, possibly multiple and complicated, and should be simply managed by discontinuing treatment with no further reintroduction of nicorandil.

8.
J Pediatr ; 197: 154-157, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29576324

RESUMO

INTRODUCTION: To assess the prevalence of nail involvement in children <16 years old with a confirmed diagnosis of scabies. STUDY DESIGN: Observational, prospective study in 7 French dermatology departments between June 2015 and January 2017. Children were included if they had scabies confirmed by dermoscopy and/or microscopy and if nails could be sampled. The first toenails and thumbnails as well as clinically affected nails were systematically sampled for microscopic examination. Individual data were recorded via a standardized questionnaire. RESULTS: A total of 47 children with scabies were included (26 females [55.3%], mean age 3.6 ± 4.0 years). Pruritus was present in 42 children (89.3%); the relapse rate was 38.3% (n = 18). In 3 infants (6.4%), Sarcoptes mites were revealed by dermoscopy or microscopy of the first toenails (2 cases) and a thumbnail (1 case), but nails were normal in 2 children. Two of the 3 infants had already received treatment for scabies in the previous weeks. CONCLUSION: Prevalence of nail involvement in children with confirmed scabies was 6.4%. Nails should not be overlooked during scabies treatment.

9.
Am J Clin Dermatol ; 19(4): 609-615, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29594973

RESUMO

BACKGROUND: Psoriasis affects 2-4% of the population, with the most common clinical type being plaque psoriasis. The linear form of psoriasis is very rare. The literature on linear psoriasis (LP) consists of only case reports, and data are few. OBJECTIVE: This study aimed to better understand LP in a large-scale study. PATIENTS AND METHODS: We retrospectively retrieved the medical records from 14 French medical centers of patients newly diagnosed clinically with LP, with or without the support of histology, between 1 February and 31 July 2015. For each case, we assessed the clinical features, treatments and treatment efficacy. RESULTS: In total, 30 cases of LP (mean age 26.8 years, 13 males) were reported. Mean age at onset of LP was 20.0 years, with 18 developing LP in childhood. Ten patients had a family history of psoriasis, and two had psoriatic arthritis. A total of 19 cases were linear at onset, with concomitant classical psoriasis; these were termed "superimposed" LP. The remaining 11 cases were not associated with classical psoriasis and were termed "isolated" LP. In four of the superimposed cases, LP developed when the patient was receiving systemic treatment: methotrexate (n = 2), etanercept (n = 1) or infliximab (n = 1). Topical steroids were effective in 76% of cases in which they were used, and systemic treatment was effective in < 66%. Treatments were less effective in LP than in classical psoriasis. DISCUSSION: We identified a wide range of LP, with two profiles: isolated LP and superimposed LP. Topical treatment usually evoked clinical response, with relative resistance to systemic therapy. Methotrexate and anti-tumor necrosis factor (TNF)-α therapies can possibly unmask LP.


Assuntos
Psoríase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/patologia , Estudos Retrospectivos , Pele/patologia , Resultado do Tratamento , Adulto Jovem
12.
Dermatol Ther ; 31(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29193624

RESUMO

Psoriasis affects 0.5-2% of children. Severe forms required use of systemic treatments. Few studies are published on efficiency and tolerance of systemic treatments in children. We conducted a survey in France to better understand management of children with psoriasis. A survey on childhood psoriasis management was sent by e-mail to GPs, pediatricians, and dermatologists. The survey included 384 physicians. Respectively 53.1%, 49.8%, and 83.3% of GPs, pediatricians, and dermatologists declare to have seen at least one child with psoriasis during the 3 previous months. Less than 5% of GPs and pediatricians used severity score versus 23.7% of dermatologists. If most of physicians declare to use local treatments, less than 5% of GPs and pediatricians used systemic treatments. 32.4% of dermatologists declared to use at least one systemic treatment, but only 2.9% to use the 4 systemic treatments available in France. This survey shows that only half of GPs and pediatricians see children with psoriasis, but most of dermatologists. However, the management of severe forms seems limited by the underuse of severity scores and systemic treatments. These results should stimulate dermatology societies to promote prospective studies and guidelines in young populations with psoriasis.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Dermatologistas/tendências , Clínicos Gerais/tendências , Pediatras/tendências , Padrões de Prática Médica/tendências , Psoríase/tratamento farmacológico , Adulto , Idade de Início , Criança , Pré-Escolar , Tomada de Decisão Clínica , Fármacos Dermatológicos/efeitos adversos , Feminino , França/epidemiologia , Pesquisas sobre Serviços de Saúde , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/epidemiologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
14.
Am J Clin Dermatol ; 19(2): 261-265, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28849428

RESUMO

BACKGROUND: Atopic dermatitis (AD) and psoriasis are chronic inflammatory cutaneous disorders for which the gold standard treatment is topical corticosteroids. Although fears about topical corticosteroids are known to be a primary cause of poor therapeutic adherence in AD, this has not been evaluated in psoriasis. TOPICOP is a helpful and easy-to-use tool for the evaluation of topical corticosteroid concerns (TCC). It may help clinicians improve adherence to treatment and correct misconceptions. OBJECTIVE: We aimed to compare the TCC of parents of children with psoriasis or AD using the TOPICOP scale and a visual analog scale (VAS). METHODS: We performed a cross-sectional multicenter study in nine French hospitals from 1 October 2015 to 31 May 2016. The TOPICOP scale was developed for patients with AD and comprises 12 questions to assess patients' worries and beliefs about topical corticosteroids, with a maximum score of 36. We used a standardized questionnaire to collect epidemiologic and medical data, and the parents completed the TOPICOP scale and VAS (score 0-10). RESULTS: A total of 122 children were enrolled (61 patients in each group). The mean Physician Global Assessment was 2.1 in the psoriasis group, and the mean SCORing AD index was 33.3 in the AD group. The TOPICOP score was 16.0 in the psoriasis group and 18.8 in the AD group (p = 0.10). The VAS score was 5.6 and 5.1 in the psoriasis and AD groups, respectively (p = 0.18). The mean TOPICOP score was higher if the mother answered (p < 0.0001; odds ratio 12.3; 95% confidence interval 9.2-15.5). In the AD group, the mean TOPICOP score was higher if follow-up for the child was as an outpatient (p = 0.018). In the psoriasis group, the mean TOPICOP score was higher if patients were seen for the first time (p = 0.047). CONCLUSION: Using the TOPICOP questionnaire and a VAS, we found the level of TCC for the parents of pediatric patients with psoriasis to be similar to that for parents of pediatric patients with AD. As TCC is an issue in patients with psoriasis, future research is warranted to assess whether therapeutic education lessens TCC and improves treatment outcomes.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Glucocorticoides/efeitos adversos , Pais/psicologia , Psoríase/tratamento farmacológico , Administração Cutânea , Adolescente , Adulto , Ansiedade/etiologia , Criança , Pré-Escolar , Estudos Transversais , Dermatite Atópica/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Cooperação do Paciente/estatística & dados numéricos , Educação de Pacientes como Assunto , Psoríase/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
15.
JAAD Case Rep ; 3(5): 454-456, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28971133
16.
Genet Med ; 19(9): 989-997, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28151489

RESUMO

PURPOSE: Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS. METHODS: We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested. RESULTS: We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03 × 10-5). We identified 40 different mutations and found strong oncogenic mutations more frequently in patients without brain overgrowth (50.6%) than in those with brain overgrowth (15.2%; P = 0.00055). Mutant allele levels were higher in skin and overgrown tissues than in blood and buccal samples (P = 3.9 × 10-25), regardless of the phenotype. CONCLUSION: Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions.Genet Med advance online publication 02 February 2017.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos de Associação Genética , Testes Genéticos , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Mutação , Adolescente , Adulto , Alelos , Substituição de Aminoácidos , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Gerenciamento Clínico , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Mosaicismo , Fenótipo , Diagnóstico Pré-Natal , Análise de Sequência de DNA , Adulto Jovem
17.
Medicine (Baltimore) ; 96(7): e6112, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28207531

RESUMO

Diseases characterized by recurrent symptoms with prolonged intervals without any clinical manifestations can pose diagnostic difficulties. Some diagnoses will be obvious but other situations can be very challenging.To nosologically delineate a new entity characterized by recurrent flares of induration of the forearms and legs with swelling of the extremities accompanied by intense fatigue and variable other symptoms.Retrospective observational study of patients recorded from 2000 to 2015. All patients included were seen during a consultation at the Dermatology Department of the University Hospital of Strasbourg, France. We retrieved the medical records from patients seen and recorded over the last 16 years having induration of the extremities, the forearm and the legs occurring between 4 and 12 hours after a physical effort accompanied by systemic signs that lasted for a few days. We analyzed in detail the clinical and biological features, evolution, and treatments of these patients.We included 6 males, with a mean age of 47 years; mean age at disease onset was 42. All patients were initially misdiagnosed as having rheumatic disorders. The mean delay before diagnosis was 5 years. The main complaint was painful induration or muscle soreness of the forearms and the legs associated with transient functional impairment and prolonged asthenia for a mean duration of 3.5 days. Induration of the deep soft tissues was very suggestive of myofasciitis. The delay between the triggering physical effort and the swelling was between 6 and 12 hours. Physical effort as triggering factor was never spontaneously mentioned. Two patients had partial response to high dose antihistamines and 2 other patients to the interleukin-1 inhibitor anakinra. One patient responded to hydroxychloroquine.The very stereotypical presentation in those 6 patients suggests that this is a recognizable entity characterized by effort-induced induration of forearms and/or legs, due to deep edematous myofascial involvement, occurring a few hours after a physical effort. We suggest to name this entity delayed effort-induced swelling with myofasciitis and systemic manifestations.


Assuntos
Braço , Edema/fisiopatologia , Perna (Membro) , Miosite/fisiopatologia , Urticária/diagnóstico , Urticária/fisiopatologia , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico/fisiologia , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Fatores de Tempo , Urticária/classificação , Urticária/tratamento farmacológico
19.
Pediatr Dermatol ; 34(1): 58-63, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27873356

RESUMO

BACKGROUND/OBJECTIVES: Little information is available on the prevalence and clinical aspects of nail involvement in children with psoriasis. The objective of this study was to evaluate the prevalence and clinical aspects of and the risk factors for nail involvement in French children with psoriasis. METHODS: We performed a multicenter, cross-sectional study in 23 French dermatology centers. All children seen during the 1-year study were systematically included. Clinical features of the nails were collected. Association with clinical aspects of the disease and comorbidities were evaluated. RESULTS: Of 313 children with psoriasis (mean age 9.1 ± 4.2 yrs; 149 boys, 164 girls), 31.1% had familial psoriasis and 30% had severe psoriasis. The mean age at onset was 6.1 ± 3.7 years. Nails were involved in 32.3% of children. The main clinical aspects were pitting (69.1%) for fingernails and onycholysis (40.0%) and pachyonychia (27.5%) for toenails. All of the fingers were involved at similar frequencies, whereas the big toe was involved twice as often as the others (p < 0.005). Nail involvement was associated with male sex (p < 0.001), palmoplantar psoriatic (p < 0.001), severity of disease (p = 0.003), and psoriatic arthritis (p = 0.03). CONCLUSION: The prevalence of nail involvement was 32.3% in children with psoriasis. Clinical aspects in children are reported, as well as clinical associations. As in adults, nail psoriasis is closely associated with psoriatic arthritis.


Assuntos
Doenças da Unha/epidemiologia , Unhas/patologia , Psoríase/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Prevalência , Fatores de Risco
20.
Am J Dermatopathol ; 38(2): 83-91, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26825155

RESUMO

Netherton syndrome (NS) is a severe genetic skin disorder, with often delayed or misleading clinical signs. The histological features of skin biopsies, usually described as a psoriasiform hyperplasia, have only been reported in isolated case reports or small case series. The aim of this study is to define, for the first time, the precise histological pattern of cutaneous lesions, in a large cohort of skin biopsies from confirmed NS patients. The study included 80 consecutive skin biopsies from 67 patients taken between January 1995 and June 2014. All were from confirmed NS patients with either a negative lympho-epithelial Kazal-type-related inhibitor (LEKTI) immunohistochemistry and/or molecular confirmation by identified mutation in SPINK5. In this cohort, the most frequent histological finding was also psoriasiform hyperplasia, but there were additional, less common, or previously unreported findings, including compact parakeratosis with large nuclei, subcorneum or intracorneum splitting, presence of clear cells in the upper epidermis or stratum corneum, dyskeratosis, dermal infiltrate with neutrophils and/or eosinophils, and dilated blood vessels in the superficial dermis. An early confirmation of the diagnosis of NS is essential for improved patient management. Thus, in the situation of a patient with an unknown skin disorder and non specific clinical presentation, the dermatopathologist may now be able to suggest the diagnosis of NS based on these newly reported characteristics. However, LEKTI immunohistochemistry remains the essential diagnostic investigation in cases with misleading or nonspecific histological features and is mandatory for the definitive diagnosis of NS in all patients.


Assuntos
Síndrome de Netherton/patologia , Pele/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Análise Mutacional de DNA , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Mutação , Síndrome de Netherton/genética , Síndrome de Netherton/metabolismo , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Proteínas Secretadas Inibidoras de Proteinases/análise , Proteínas Secretadas Inibidoras de Proteinases/genética , Estudos Retrospectivos , Inibidor de Serinopeptidase do Tipo Kazal 5 , Pele/química , Adulto Jovem
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