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1.
Medicine (Baltimore) ; 103(9): e37335, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428853

RESUMO

RATIONALE: Darier disease (DD) is a rare autosomal dominant disorder that primarily manifests as hyperkeratotic papules and itching. The underlying etiology of DD is pathogenic variation in the ATP2A2 gene. However, this disease has a high penetrance but variable expressivity, indicating that patients inheriting the genotype may have different manifestations due to exogenous factors. Meanwhile, a few reports have documented that COVID-19 may be implicated in the flare of DD. PATIENT CONCERNS: A 51-year-old man presented with keratotic papules and scaly erythematous rash on his trunk with pruritus after being infected with COVID-19. Laboratory test results were normal. Histological analysis revealed epidermal hyperkeratosis and intraepidermal lacunae containing dyskeratinized cells. Genetic analysis revealed a novel variant of ATP2A2 (c.815G>A, p.Trp272*), which was considered pathogenic in this case. DIAGNOSES: The patient was diagnosed as having DD. INTERVENTIONS: Oral acitretin and topical corticosteroid hormone ointments were used. OUTCOMES: The patient achieved complete resolution of symptoms during the 3-month follow-up period. LESSONS: We revealed the first novel ATP2A2 variant (c.815G>A, p.Trp272*) in the flare of DD following COVID-19 infection. Additionally, this pathogenic variant enriches the ATP2A2 gene mutation spectrum.


Assuntos
COVID-19 , Doença de Darier , Masculino , Humanos , Pessoa de Meia-Idade , Doença de Darier/complicações , Doença de Darier/genética , Doença de Darier/patologia , COVID-19/complicações , Mutação , Genótipo , Prurido , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
2.
J Drugs Dermatol ; 23(1): 1274-1277, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206153

RESUMO

BACKGROUND: Keratosis pilaris (KP) is a benign dermatosis consisting of folliculocentric keratotic papules or pustules with surrounding erythema, often on proximal extensor surfaces of extremities. Management strategies for KP largely center on moisturization and exfoliation. Urea, a well-established ingredient in topical skincare, is a component of the natural moisturizing factors with concentration-dependent humectant, emollient, and exfoliative properties.  Given the overlap of urea’s properties and management goals of KP, a 4-week, open-label, noncomparative clinical study was conducted to evaluate a moisturizing cream formulated with 20% urea for use in KP.  Thirty participants aged 18 to 65 years with KP completed this study. After a 5-day washout period, study participants applied a 20% urea cream once daily to areas of KP for 4 weeks. At baseline, 1-week, and 4-week visits, clinical grading of skin texture, adverse event monitoring, and participant satisfaction questionnaires were conducted. After 1 week and 4 weeks of product use, the percent change in skin smoothness/texture from baseline was significant (P≤0.001). Furthermore, after 4 weeks of use, the majority of participants indicated satisfaction with the feel of their skin, as well as improved confidence and decreased embarrassment related to their skin. No significant adverse events were reported. Overall, the results of this study support that 20% urea cream is generally well tolerated and suitable for use in treating KP. J Drugs Dermatol. 2024;23(1):1274-1277.     doi:10.36849/JDD.7806.


Assuntos
Anormalidades Múltiplas , Doença de Darier , Sobrancelhas , Humanos , Emolientes , Emoções , Excipientes , Sobrancelhas/anormalidades , Pele
4.
Photodiagnosis Photodyn Ther ; 45: 103892, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37951326

RESUMO

Darier's disease is a rare, genetically determined dyskeratotic skin disorder. Although many conventional treatments have been reported, management of Darier's disease remains challenging. Most patients are at high risk of recurrence during long-term follow-up. Here, we present two patients who were successfully treated with ALA photodynamic therapy (PDT) and ablative 2940 nm Er:YAG fractional laser. Both patients exhibited significant improvements in the affected areas with moderate pain, transient erythema and edema. Remission durations of up to 2 years were observed in both patients after combination treatment. Our findings suggest that the combination of ALA-PDT and 2940 nm fractional Er:YAG laser may be an effective, safe and well-tolerated treatment option for Darier's disease.


Assuntos
Doença de Darier , Lasers de Estado Sólido , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Doença de Darier/tratamento farmacológico , Fotoquimioterapia/métodos , Lasers de Estado Sólido/uso terapêutico , Terapia Combinada
5.
Vet Dermatol ; 35(2): 126-137, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37867253

RESUMO

BACKGROUND: A combination of dermoscopic and histological findings may provide useful information for the diagnosis of hair follicle diseases. However, there are no studies on dermoscopic-histopathological correlations in dogs affected by alopecia X, and comparison of longitudinal versus transversal sectioning of skin biopsy specimens in the assessment of this hair loss disorder has not been thoroughly investigated. HYPOTHESIS/OBJECTIVES: The aim of this study was to correlate dermoscopic and histological features using both longitudinal and transversal sectioning of skin biopsy samples to gain additional information for the diagnosis of alopecia X. ANIMALS: Nineteen Pomeranian dogs affected by alopecia X and five healthy Pomeranians as controls. MATERIALS AND METHODS: Dermoscopic-histological correlation was performed within the diseased group, whereas histological comparisons against controls. The demographic and clinical characteristics also were related to the histological findings. RESULTS: The dermoscopic findings revealed scattered, thinned, short hairs mixed with amorphous keratoseborrhoeic-like material (follicular plugging), perifollicular and intrafollicular scaling, and hyperpigmentation varying from pinpoint black spots to a diffuse texture. Dermoscopic findings correlated with histological findings for selected qualitative and quantitative findings. The usefulness of transversal sections was demonstrated in accurately determining the hair follicular density and counts, growth arrest phases and in identifying mineralisation of hair follicle basement membrane when compared to the longitudinal. Conversely, no correlations between histological findings and demographic and clinical characteristics were detected. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide evidence of the usefulness of dermoscopic evaluation as an accessory diagnostic tool and of transversal sections of skin biopsies as complementary to the diagnosis of alopecia X.


Assuntos
Alopecia , Doença de Darier , Animais , Cães , Alopecia/diagnóstico , Alopecia/veterinária , Alopecia/patologia , Cabelo/patologia , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/patologia , Pele/patologia , Doença de Darier/patologia , Doença de Darier/veterinária
7.
J Eur Acad Dermatol Venereol ; 38(2): 419-429, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37863661

RESUMO

BACKGROUND: Hailey-Hailey disease (HHD) remains a difficult-to-treat dermatosis and little is known about the patient's perception of the disease activity, the treatment success and its impact on quality-of-life (QoL). OBJECTIVE: To obtain better understanding of HHD patients' needs regarding their medical condition, financial burden, QoL, subjective well-being and treatment thereof as well as satisfaction to evaluate common treatments' 'real-life' relevance. METHODS: With initiation of the national registry for Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH) MDHHgermany, patients with HHD diagnosis were included starting June 2020. To assess subjective symptoms, patients filled out questionnaires such as the DLQI (dermatological life quality index), numeric rating scale (NRS) for itch, pain and burning sensation, as well as the SWLS (satisfaction with life scale) questionnaire to quantify overall satisfaction in life. Additionally, data on therapies were collected along with the patients' satisfaction of those and their medical care. Furthermore, patients assessed financial aspects and work ability. RESULTS: One hundred and two patients were recruited from dermatology clinics, office-based dermatologists and self-help platforms across Germany between June 2020 and February 2023, 90 were eligible and analysed (mean: 49.91 years, 73.33% females, 26.67% males). 39.77% stated according to the DLQI their life is severely/very severely affected. Satisfaction with life was mediocre. Burning sensation was most pronounced among subjective symptoms (NRS 5.85 ± 2.80). Systemic treatments were rated as ineffective according to 56.92%, 25.56% had never received one. Most prescribed systemic treatments were corticosteroids (73.8%), followed by low-dose naltrexone (LDN) (26.2%), retinoids (15.4%) and antibiotics (13.8%). Satisfaction with medical care was generally low. CONCLUSION: Our 'real-life' data state a major disease burden and impact on the QoL for affected individuals, as well as limited disease control due to inadequate therapies. MDHHgermany can provide insights into improvement of healthcare support with this debilitating disease and improve QoL. In the long term, it aims to provide basis for further clinical trials, epidemiological studies and immunological investigations.


Assuntos
Doença de Darier , Pênfigo Familiar Benigno , Masculino , Feminino , Humanos , Pênfigo Familiar Benigno/tratamento farmacológico , Qualidade de Vida , Objetivos , Doença de Darier/tratamento farmacológico , Naltrexona
8.
J Dermatol ; 51(2): 253-260, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087855

RESUMO

Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-linked hereditary disorder characterized by the triad of follicular hyperkeratosis-photophobia-alopecia. The clinical heterogeneity makes the diagnosis difficult. To investigate the clinicopathologic and trichoscopic features of KFSD and to further clarify the essential requisites for the diagnosis, we conducted a retrospective study of patients with KFSD. The clinical information, histologic features, and trichoscopic findings were evaluated. Eight patients were from seven separate families. Two females were mother and daughter from the same family and the other six patients were male and represented sporadic cases. The average age of onset of alopecia was 21.25 years. Involvement of the scalp hairs leading to progressive scarring alopecia on the midline of the scalp with variable degrees of inflammation was the pathognomonic feature. It typically began after puberty. Vellus hair-associated follicular hyperkeratosis affected all of the patients. However, photophobia was not a constant feature. Histopathologic examination revealed disorders of the hair follicle with an acute-chronic inflammatory response. Follicular changes including fused infundibulum, the protrusion of the outer root sheath into the follicular canal, and a dilatation of the follicles at the isthmus level caused by the occlusion of keratin were observed. The trichoscopic features included perifollicular scaling, tufted hairs, and loss of follicular openings. In conclusion, terminal hair involvement, either scalp hairs, eyebrows, or eyelashes, and the hyperkeratosis of the follicle of vellus hairs is the diagnostic basis of KFSD. We hypothesize that follicular changes in histopathology are the primary event that trigger variable inflammation and further follicular destruction.


Assuntos
Anormalidades Múltiplas , Doença de Darier , Sobrancelhas , Doenças Genéticas Ligadas ao Cromossomo X , Ictiose , Dermatopatias Genéticas , Feminino , Humanos , Masculino , Adulto Jovem , Adulto , Sobrancelhas/patologia , Estudos Retrospectivos , Doença de Darier/diagnóstico , Doença de Darier/patologia , Alopecia/patologia , Fotofobia/patologia , Inflamação/patologia
9.
Acta Dermatovenerol Alp Pannonica Adriat ; 32(4): 191-195, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38126103

RESUMO

Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.


Assuntos
Doença de Darier , Fármacos Dermatológicos , Adolescente , Humanos , Feminino , Doença de Darier/tratamento farmacológico , Alitretinoína/uso terapêutico , Acitretina/uso terapêutico , Isotretinoína/uso terapêutico , Fármacos Dermatológicos/uso terapêutico
10.
Eur Rev Med Pharmacol Sci ; 27(21): 10705-10715, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37975396

RESUMO

BACKGROUND: Perforating dermatoses are heterogeneous skin disorders characterized by transepidermal elimination of dermal tissue components. Acquired perforating dermatoses can be divided into four types, according to the eliminated dermal materials: Kyrle disease, perforating reactive collagenosis, elastosis perforans serpiginosa, and perforating folliculitis. They characterize adult patients with coexisting systemic diseases, regardless of the dermal materials eliminated. The association between Kyrle disease and renal failure or diabetes mellitus is common. CASE REPORT: We reported the case of Kyrle disease in a patient with chronic kidney disease. A literature review was performed with the aim to highlight the associated comorbidities and point out the role of early and specific treatment of the cutaneous symptoms and manifestations. CONCLUSIONS: Being Kyrle disease a pruritic condition which adversely affects the patient's quality of life, it would be desirable to place greater therapeutic attention on the alleviation of itching and on the correct management of the underlying comorbidity.


Assuntos
Doenças do Colágeno , Doença de Darier , Foliculite , Dermatopatias , Adulto , Humanos , Qualidade de Vida , Doença de Darier/diagnóstico , Doença de Darier/complicações , Foliculite/complicações , Doenças do Colágeno/complicações , Doenças do Colágeno/diagnóstico , Prurido/complicações
11.
Nat Commun ; 14(1): 7470, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978298

RESUMO

Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD.


Assuntos
Doença de Darier , Humanos , Doença de Darier/genética , Doença de Darier/metabolismo , Doença de Darier/patologia , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-23/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Pele/patologia , Células Th17/metabolismo
12.
J Drugs Dermatol ; 22(10): 985-989, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37801530

RESUMO

Keratosis pilaris (KP) is a chronic disorder of follicular hyperkeratinization and perifollicular erythema with lesions affecting the extensor surfaces of arms, upper legs, and buttocks. While there is some evidence that laser therapies and topical therapies such as lactic acid reduce the follicular papules of KP, support is limited with respect to which topical treatments dermatologists utilize and their perception of efficacy. A 16-question survey was distributed to a random sampling of the ODAC Conference listserv to determine which topical treatments dermatologists utilize the most, the duration of therapy needed with various treatment modalities, and the effectiveness of topical and laser therapy for treating KP. Our study found topical lactic acid is the most used first-line therapy for KP (43.63% of survey respondents), followed by salicylic acid (20.72%). Laser therapy is only utilized by 8.76% of survey respondents, with a lack of insurance coverage and proper equipment limiting its use. KP is often recalcitrant to treatment, and our study demonstrated that over 60% of respondents found recurrence of KP lesions within three months of stopping salicylic acid treatment and OTC moisturizer treatment. The data herein can be used to better utilize the selection of topical and laser therapies for the treatment of KP. J Drugs Dermatol. 2023;22(10):985-989 doi:10.36849/JDD.7534.


Assuntos
Doença de Darier , Dermatologistas , Humanos , Doença de Darier/diagnóstico , Doença de Darier/terapia , Doença de Darier/patologia , Ácido Salicílico/uso terapêutico , Ácido Láctico
16.
JCI Insight ; 8(18)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37561594

RESUMO

Mutation of the ATP2A2 gene encoding sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) was linked to Darier disease more than 2 decades ago; however, there remain no targeted therapies for this disorder causing recurrent skin blistering and infections. Since Atp2a2-knockout mice do not phenocopy its pathology, we established a human tissue model of Darier disease to elucidate its pathogenesis and identify potential therapies. Leveraging CRISPR/Cas9, we generated human keratinocytes lacking SERCA2, which replicated features of Darier disease, including weakened intercellular adhesion and defective differentiation in organotypic epidermis. To identify pathogenic drivers downstream of SERCA2 depletion, we performed RNA sequencing and proteomics analysis. SERCA2-deficient keratinocytes lacked desmosomal and cytoskeletal proteins required for epidermal integrity and exhibited excess MAPK signaling, which modulates keratinocyte adhesion and differentiation. Immunostaining patient biopsies substantiated these findings, with lesions showing keratin deficiency, cadherin mislocalization, and ERK hyperphosphorylation. Dampening ERK activity with MEK inhibitors rescued adhesive protein expression and restored keratinocyte sheet integrity despite SERCA2 depletion or chemical inhibition. In sum, coupling multiomic analysis with human organotypic epidermis as a preclinical model, we found that SERCA2 haploinsufficiency disrupts critical adhesive components in keratinocytes via ERK signaling and identified MEK inhibition as a treatment strategy for Darier disease.


Assuntos
Doença de Darier , Camundongos , Animais , Humanos , Doença de Darier/tratamento farmacológico , Doença de Darier/genética , Doença de Darier/metabolismo , Epiderme/metabolismo , Queratinócitos/metabolismo , Retículo Endoplasmático/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
19.
Microbiome ; 11(1): 162, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496039

RESUMO

BACKGROUND: Darier's disease (DD) is a genodermatosis caused by mutations of the ATP2A2 gene leading to disrupted keratinocyte adhesion. Recurrent episodes of skin inflammation and infections with a typical malodour in DD indicate a role for microbial dysbiosis. Here, for the first time, we investigated the DD skin microbiome using a metabarcoding approach of 115 skin swabs from 14 patients and 14 healthy volunteers. Furthermore, we analyzed its changes in the context of DD malodour and the cutaneous DD transcriptome. RESULTS: We identified a disease-specific cutaneous microbiome with a loss of microbial diversity and of potentially beneficial commensals. Expansion of inflammation-associated microbes such as Staphylococcus aureus and Staphylococcus warneri strongly correlated with disease severity. DD dysbiosis was further characterized by abundant species belonging to Corynebacteria, Staphylococci and Streptococci groups displaying strong associations with malodour intensity. Transcriptome analyses showed marked upregulation of epidermal repair, inflammatory and immune defence pathways reflecting epithelial and immune response mechanisms to DD dysbiotic microbiome. In contrast, barrier genes including claudin-4 and cadherin-4 were downregulated. CONCLUSIONS: These findings allow a better understanding of Darier exacerbations, highlighting the role of cutaneous dysbiosis in DD inflammation and associated malodour. Our data also suggest potential biomarkers and targets of intervention for DD. Video Abstract.


Assuntos
Doença de Darier , Humanos , Doença de Darier/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Disbiose , Pele , Inflamação
20.
Sci Rep ; 13(1): 10160, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349344

RESUMO

This work reports a high-performance, low-cost, biocompatible triboelectric nanogenerator (TENG) using chicken skin (CS). The device is suitable to power wearable devices, which is critical to adapt electronics in monitoring, predicting, and treating people. It also supports sustainability by providing a cost-effective way to reduce the poultry industry's waste. It has been shown here that CS-derived biowaste is an effective means of generating tribopositive material for TENGs. The CS contains amino acid functional groups based on (Glycine, Proline, and Hydroxyproline), which are essential to demonstrate the electron-donating ability of collagen. The skin was cut into 3 × 3 cm2 and used as the raw material for fabricating the TENG device with a stacking sequence of Al/Kapton/spacing/CS/Al. The chicken skin-based TENG (CS-TENG) is characterized at different frequencies (4-14 HZ) using a damping system. The CS-TENG produces an open-circuit voltage of 123 V, short-circuit current of 20 µA and 0.2 mW/cm2 of a power density at 20 MΩ. The biocompatible CS-TENG presents ultra-robust and stable endurance performance with more than 52,000 cycles. The CS-TENG is impressively capable of scavenging energy to light up to 55 commercial light-emitting diodes (LEDs), a calculator, and to measure the physiological motions of the human body. CS-TENG is a step toward sustainable, battery-less devices or augmented energy sources, especially when using traditional power sources, such as in wearable devices, remote locations, or mobile applications is not practical or cost-effective.


Assuntos
Galinhas , Doença de Darier , Humanos , Animais , Pele , Aminoácidos
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