RESUMEN
BACKGROUND: Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown. OBJECTIVES: To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD). METHODS: We used questionnaire-derived and genotype data from the European population-based Lifelines cohort and biobank. We performed a discovery genome-wide association study (GWAS) of HE (2879 cases and 16 249 controls) and of AD (1706 cases and 17 190 controls). We replicated our findings in an independent Lifelines sample for HE (1188 cases and 6431 controls) and AD (757 cases and 6747 controls). We conducted several post-GWAS analyses and performed genetic correlation analyses between our HE results and independent AD data. RESULTS: The two-step GWAS of HE, regardless of adjusting for AD, identified one independent locus 20q13.33, likely driven by a number of causal single-nucleotide polymorphisms. For the AD GWAS, we replicated a known stop-gained rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p < 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63). CONCLUSIONS: Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD.
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Dermatitis Atópica , Eccema , Estudio de Asociación del Genoma Completo , Dermatosis de la Mano , Polimorfismo de Nucleótido Simple , Humanos , Dermatitis Atópica/genética , Masculino , Eccema/genética , Femenino , Dermatosis de la Mano/genética , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Genotipo , Sitios Genéticos , Proteínas FilagrinaRESUMEN
BACKGROUND: No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin-tape strips for molecular investigations enable noninvasive investigations of HE. OBJECTIVE: By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated. METHODS: Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed. RESULTS: The largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such as EPHA1. CONCLUSION: Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.
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Dermatosis de la Mano/diagnóstico , Dermatosis de la Mano/genética , Manejo de Especímenes/métodos , Cinta Quirúrgica , Transcriptoma , Adulto , Anciano , Biomarcadores/metabolismo , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/genética , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/genética , Dermatitis Irritante/diagnóstico , Dermatitis Irritante/genética , Diagnóstico Diferencial , Regulación hacia Abajo , Femenino , Dermatosis de la Mano/inmunología , Humanos , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Receptor EphA1/metabolismo , Piel/inmunología , Piel/metabolismo , Secuenciación del ExomaRESUMEN
Hand eczema is a common inflammatory skin condition of the hands whose pathogenesis is largely unknown. More insight and knowledge of the disease on a more fundamental level might lead to a better understanding of the biological processes involved, which could provide possible new treatment strategies. We aimed to profile the transcriptome of lesional palmar epidermal skin of patients suffering from vesicular hand eczema using RNA-sequencing. RNA-sequencing was performed to identify differentially expressed genes in lesional vs. non-lesional palmar epidermal skin from a group of patients with vesicular hand eczema compared to healthy controls. Comprehensive real-time quantitative PCR analyses and immunohistochemistry were used for validation of candidate genes and protein profiles for vesicular hand eczema. Overall, a significant and high expression of genes/proteins involved in keratinocyte host defense and inflammation was found in lesional skin. Furthermore, we detected several molecules, both up or downregulated in lesional skin, which are involved in epidermal differentiation. Immune signalling genes were found to be upregulated in lesional skin, albeit with relatively low expression levels. Non-lesional patient skin showed no significant differences compared to healthy control skin. Lesional vesicular hand eczema skin shows a distinct expression profile compared to non-lesional skin and healthy control skin. Notably, the overall results indicate a large overlap between vesicular hand eczema and earlier reported atopic dermatitis lesional transcriptome profiles, which suggests that treatments for atopic dermatitis could also be effective in (vesicular) hand eczema.
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Eccema/fisiopatología , Dermatosis de la Mano/fisiopatología , Adulto , Anciano , Estudios de Casos y Controles , Eccema/genética , Femenino , Dermatosis de la Mano/genética , Humanos , Masculino , Persona de Mediana Edad , Transcriptoma , Adulto JovenRESUMEN
Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French-Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools.
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Epidermólisis Ampollosa Simple/genética , Queratina-14/genética , Queratina-15/genética , Simulación por Computador , Epidermólisis Ampollosa Simple/patología , Femenino , Dermatosis del Pie/genética , Úlcera del Pie/genética , Úlcera del Pie/patología , Dermatosis de la Mano/genética , Heterocigoto , Humanos , Persona de Mediana Edad , Mutación Missense , Enfermedades de la Uña/genética , FenotipoRESUMEN
Autosomal recessive congenital ichthyosis (ARCI) manifests with generalized scaling often associated with generalized erythema. Mutations in at least 13 different genes have been reported to cause ARCI. Acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder manifesting with peeling over the distal limbs and dorsal surfaces of hands and feet. APSS is mostly due to mutations in TGM5, encoding transglutaminase 5. Both ARCI and APSS are fully penetrant genetic traits. Here, we describe a consanguineous family in which one patient with mild ARCI was found to carry a homozygous mutation in ALOXE3 (c.1238G > A; p.Gly413Asp). The patient was also found to carry a known pathogenic homozygous mutation in TGM5 (c.1335G > C; p.Lys445Asn) but did not display acral peeling skin. Her uncle carried the same homozygous mutation in TGM5 but carried the ALOXE3 mutation in a heterozygous state and showed clinical features typical of APSS. Taken collectively, these observations suggested that the ALOXE3 mutation suppresses the clinical expression of the TGM5 variant. We hypothesized that ALOXE3 deficiency may affect the expression of a protein capable of compensating for the lack of TGM5 expression. Downregulation of ALOXE3 in primary human keratinocytes resulted in increased levels of corneodesmosin, which plays a critical role in the maintenance of cell-cell adhesion in the upper epidermal layers. Accordingly, ectopic corneodesmosin expression rescued the cell-cell adhesion defect caused by TGM5 deficiency in keratinocytes as ascertained by the dispase dissociation assay. The present data thus provide evidence for phenotypic suppression in a human hereditary skin disorder.
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Adhesión Celular/genética , Dermatitis Exfoliativa/genética , Ictiosis Lamelar/genética , Lipooxigenasa/genética , Enfermedades Cutáneas Genéticas/genética , Transglutaminasas/genética , Células Cultivadas , Niño , Análisis Mutacional de ADN , Dermatitis Exfoliativa/complicaciones , Células Epidérmicas/fisiología , Femenino , Dermatosis del Pie/genética , Dermatosis de la Mano/genética , Heterocigoto , Homocigoto , Humanos , Ictiosis Lamelar/complicaciones , Masculino , Linaje , Fenotipo , Cultivo Primario de Células , Enfermedades Cutáneas Genéticas/complicaciones , Secuenciación del ExomaRESUMEN
BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease. Its classification as a variant of psoriasis is controversial. Exogenous factors may affect PPP. OBJECTIVES: Occupational aspects of PPP based on a retrospective evaluation of patient data are discussed. METHODS: Data from 1518 patients who took part in a tertiary prevention program (TIP) for occupational skin diseases in our department between January 2015 and June 2019 were evaluated. RESULTS: PPP was diagnosed in 30 patients (1.98%). The hands were affected in all of them, while concomitant feet involvement was found in 83.3%. The majority was female (70.0%) and reported tobacco smoking (83.3%). Systemic treatment was continued or initiated in one third of patients. In only 8 patients (26.7%) was PPP considered to be work-related. CONCLUSIONS: PPP is an endogenous disease which is influenced by nonoccupational factors (e.g., tobacco smoking). Therefore, a thorough investigation is mandatory when assessing whether occupational factors are legally essential and exceed aggravation by everyday life. For this purpose, a well-documented course of the disease and a critical appraisal of occupational and nonoccupational factors are crucial. Only if occupational causality is probable can preventive measures be provided by the statutory accident insurance and PPP can be legally recognized as an occupational disease.
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Dermatosis del Pie , Dermatosis de la Mano , Psoriasis , Enfermedades Cutáneas Vesiculoampollosas , Enfermedad Crónica , Femenino , Dermatosis del Pie/diagnóstico , Dermatosis del Pie/genética , Dermatosis de la Mano/diagnóstico , Dermatosis de la Mano/genética , Humanos , Psoriasis/diagnóstico , Psoriasis/genética , Estudios RetrospectivosRESUMEN
We describe a 43-year-old woman with a 10-year history of grossly hyperkeratotic nodules which progressively extended over the right ring finger. These involuted leaving pale, atrophic skin in their wake. At presentation, the advancing border had an arciform series of nodules in the pattern of keratoacanthoma centrifugum marginatum. The presence of filiform keratinisation that encased the nail plate, gross onychogryphotic masses of keratin on the ventral finger surface and a flat nail-like plate of keratin on the dorsal finger surface were distinctive features. Skin biopsy showed epidermal acanthosis, gross papillomatous cutaneous horn formation that had onycholemmal features. The pathology differed from keratoacanthoma and was not crateriform or infundibulocystic. Although HPV was not detected on immunohistochemistry, pathogenesis may still represent an HPV-related transfection of onycholemmal keratin committed stem cells producing an onycholemmal variant of keratoacanthoma centrifugum marginatum. A conceptual model linked to advances in follicular stem cell biology is formulated to explore this case.
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Dermatosis de la Mano/genética , Queratoacantoma/genética , Enfermedades de la Uña/genética , Adulto , Femenino , Dedos , Dermatosis de la Mano/patología , Humanos , Queratoacantoma/patología , Mutación , Enfermedades de la Uña/patología , Células MadreRESUMEN
BACKGROUND: Filaggrin is an important protein for structure and function of the skin barrier. Filaggrin gene (FLG) mutations are known to result in dry skin, impaired skin barrier, and increased risk for atopic dermatitis. However, it is not clear whether these mutations are associated with contact allergy or hand eczema in adolescence. OBJECTIVES: The purpose of this study was to investigate whether FLG mutations are associated with contact allergy, self-reported hand eczema, or dry skin in adolescence. METHODS: We used data from the 16-year follow-up in the BAMSE cohort, information obtained from a Web-based questionnaire including questions on hand eczema and dry skin, from FLG mutation analysis (R501X, R2447X, 2282del4), and patch testing (n = 1822). RESULTS: Logistic regression analyses showed no statistically significant associations between FLG mutations and contact allergy (any contact allergy, nickel allergy, or fragrance allergy) according to patch test, or self-reported hand eczema at 16 years, or hand eczema ever. However, FLG mutations were associated with self-reported dry skin at 16 years. CONCLUSIONS: FLG mutations are associated with self-reported dry skin at 16 years. However, in this study no consistent associations were found between FLG mutations and contact allergy or hand eczema at 16.
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Dermatitis Alérgica por Contacto/genética , Dermatosis de la Mano/genética , Mutación , Proteínas S100/genética , Adolescente , Femenino , Proteínas Filagrina , Humanos , Masculino , Níquel/efectos adversos , Perfumes/efectos adversos , Análisis de Regresión , Factores de Riesgo , Autoinforme , Fenómenos Fisiológicos de la PielRESUMEN
BACKGROUND: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. OBJECTIVE: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. METHODS: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. RESULTS: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p>0.1). STUDY LIMITATION: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. CONCLUSIONS: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.
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Interleucinas/genética , Mutación , Psoriasis/genética , Adulto , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Pueblo Asiatico/genética , China , Femenino , Dermatosis del Pie/genética , Dermatosis del Pie/patología , Estudios de Asociación Genética , Dermatosis de la Mano/genética , Dermatosis de la Mano/patología , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Psoriasis/patología , Análisis de Secuencia de ADN , Estadísticas no ParamétricasRESUMEN
Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Psoriasis/genética , Interleucinas/genética , Mutación , Fenotipo , Psoriasis/patología , China , Análisis de Secuencia de ADN , Estadísticas no Paramétricas , Pueblo Asiatico/genética , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Estudios de Asociación Genética , Dermatosis del Pie/genética , Dermatosis del Pie/patología , Dermatosis de la Mano/genética , Dermatosis de la Mano/patología , HeterocigotoRESUMEN
BACKGROUND: There are no Indian studies on the association between filaggrin gene (FLG) mutations and any dermatosis, including hand eczema. OBJECTIVES: To determine the prevalence of FLG mutations in Indian hand eczema patients, and examine associations between such mutations and any aetiological type of hand eczema. MATERIALS AND METHODS: A total of 163 patients and 86 controls were included. Patients were categorized into aetiological subtypes of hand eczema. FLG polymorphisms (S2889X, 2282del4, R501X, and Q2417X) were determined in patients and controls, and correlated with subtypes. RESULTS: The prevalences of FLG mutations were 33.7% in cases and 3.5% in controls. Mutations in S2889X constituted 96.4% of all FLG mutations. No carrier of R501X and Q2417X mutations was identified. Among 55 patients with mutations, irritant contact dermatitis (ICD) with or without atopy was found in 22 patients, allergic contact dermatitis (ACD) with or without atopy was found in 12, and idiopathic hand eczema was found in 12. There was a significant association of FLG mutations with ICD with or without atopy, ACD without atopy, and idiopathic subtypes. FLG mutations were associated with more severe hand eczema. CONCLUSIONS: S2889X mutation is commoner in patients than in controls. FLG polymorphisms are associated with specific subtypes of hand eczema and severe disease.
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Dermatitis Alérgica por Contacto/genética , Dermatitis Atópica/genética , Dermatitis Irritante/genética , Dermatosis de la Mano/genética , Proteínas de Filamentos Intermediarios/genética , Mutación , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Proteínas Filagrina , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Prospectivos , Proteínas S100 , Adulto JovenRESUMEN
BACKGROUND: Knowledge about the skin deposition and penetration of nickel into the stratum corneum (SC) after short contact with metallic items is limited. OBJECTIVE: To quantify nickel skin deposition and penetration into the SC after short contact with metallic nickel. METHODS: Sixteen nickel-allergic participants and 10 controls were exposed to 3 pure nickel discs and 1 aluminium disc on each volar forearm for 3 × 10 minutes. Before exposure, 1 forearm was irritated with 0.5% sodium lauryl sulfate under 24-hour occlusion. Immediately, as well as 24 and 72 hours after metallic disc exposure, outer SC layers were removed with adhesive tapes and the nickel content was measured. RESULTS: Nickel deposition and SC penetration capable of eliciting allergic nickel dermatitis were found immediately and after 24 hours. Significantly higher nickel amounts were found on normal skin and in the SC of nickel-allergic participants than in controls both immediately and after 24 hours, and on irritated skin immediately after exposure. CONCLUSIONS: Nickel deposition and SC penetration is considerable after nickel skin exposure of 3 × 10 minutes. Combined with the allergic responses resulting from the same exposures reported previously, this study highlights that short skin exposure to nickel-releasing items may cause allergic nickel dermatitis.
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Quelantes/metabolismo , Dermatitis Alérgica por Contacto/metabolismo , Níquel/metabolismo , Absorción Cutánea , Piel/metabolismo , Adulto , Aluminio/metabolismo , Quelantes/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/genética , Dermatitis Atópica/genética , Femenino , Proteínas Filagrina , Dermatosis de la Mano/genética , Humanos , Proteínas de Filamentos Intermediarios/genética , Masculino , Persona de Mediana Edad , Mutación , Níquel/efectos adversosRESUMEN
Epidermolysis bullosa is a group of inherited blistering skin diseases resulting in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal epidermal keratins 5 and 14. Here, we present a patient diagnosed with a localized subtype of epidermolysis bullosa simplex caused by a heterozygous mutation p.Ala428Asp in the KRT5 gene, that has not been previously identified. Moreover, a bioinformatic analysis of the novel mutation was performed, showing changes in the interaction network between the proteins. Identification of novel mutations and genotype-phenotype correlations allow to better understanding of underlying pathophysiologic bases and is important for genetic counselling, patients' management, and disease course prediction.
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Epidermólisis Ampollosa Simple/genética , Queratina-5/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Epidermólisis Ampollosa Simple/patología , Femenino , Dermatosis del Pie/genética , Estudios de Asociación Genética , Dermatosis de la Mano/genética , Heterocigoto , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Lactante , Queratina-5/química , Simulación de Dinámica Molecular , Mutación Missense , Conformación Proteica , Estabilidad Proteica , Alineación de Secuencia , Lengua/patologíaAsunto(s)
Dermatosis de la Mano/genética , Mosaicismo , Pubertad/genética , Telangiectasia/genética , Niño , Humanos , MasculinoAsunto(s)
Adenosina Desaminasa/genética , Predisposición Genética a la Enfermedad , Trastornos de la Pigmentación/congénito , Proteínas de Unión al ARN/genética , Luz Solar , Xerodermia Pigmentosa/diagnóstico , Niño , Diagnóstico Diferencial , Dermatosis de la Mano/genética , Dermatosis de la Mano/patología , Humanos , Hiperpigmentación/genética , Hiperpigmentación/patología , Masculino , Trastornos de la Pigmentación/genética , PronósticoAsunto(s)
Cardiomiopatías/diagnóstico , Enfermedades del Cabello/genética , Dermatosis de la Mano , Queratodermia Palmoplantar , Disfunción Ventricular Izquierda/diagnóstico , Adulto , Dermatosis de la Mano/genética , Dermatosis de la Mano/patología , Humanos , Queratodermia Palmoplantar/genética , Queratodermia Palmoplantar/patología , MasculinoRESUMEN
BACKGROUND: Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. OBJECTIVES: To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. METHODS: Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of the hands of 15 Caucasian women. Biopsies from lesional and adjacent nonlesional (NL) areas were processed for histological analysis or gene expression profiling. RESULTS: Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared with NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL vs. NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. CONCLUSIONS: Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. In particular, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.
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Matriz Extracelular/patología , Lentigo/patología , Trastornos por Fotosensibilidad/patología , Piel/patología , Anciano , Dorso , Dermoscopía , Epidermis/metabolismo , Matriz Extracelular/metabolismo , Femenino , Perfilación de la Expresión Génica , Genes/genética , Dermatosis de la Mano/genética , Dermatosis de la Mano/metabolismo , Dermatosis de la Mano/patología , Humanos , Lentigo/genética , Melaninas/metabolismo , Melanocitos/metabolismo , Persona de Mediana Edad , Trastornos por Fotosensibilidad/genética , Piel/metabolismo , Transcriptoma/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Atopic dermatitis and hand eczema often impair the ability of people to work. Only a few studies have investigated whether individuals with loss-of-function filaggrin gene (FLG) mutations, who often have severe and early onset of dermatitis, experience occupational consequences. OBJECTIVE: To investigate the personal consequences of having atopic dermatitis and/or hand eczema and FLG mutations. METHOD: Adult Danes from the general population (n = 3247) and patients with atopic dermatitis and/or hand eczema (n = 496) were genotyped for common FLG mutations, and completed a questionnaire about skin symptoms and hand eczema. Socioeconomic variables, including disability pension, and information on work in risk occupations were retrieved from national registries. The reasons for granting disability pension were unknown. RESULTS: Disability pension was associated with hand eczema in the general population, especially among individuals with a history of atopic dermatitis. Moreover, self-reported hand eczema and atopic dermatitis were associated with particularly high risk of disability pension among FLG mutation carriers [odds ratio (OR) 4.02 and 95% confidence interval (CI): 1.15-14.11; and OR 6.01 and 95%CI: 2.37-15.34, respectively]. Furthermore, 60% of the FLG mutation carriers with atopic dermatitis who developed hand eczema had experienced symptoms before adulthood. CONCLUSION: In the general population, self-reported hand eczema and atopic dermatitis, particularly in individuals with a genetically impaired skin barrier, were associated with disability pension, suggesting that FLG mutations carriers with a history of atopic dermatitis and hand eczema could benefit from early attention with respect to choice of occupation.