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Background

Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75  90%), which appear to be underestimated.

Objective

To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses.

Methods

We studied 31 patients (47.0 ± 13.2 years old, range 15–71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs).

Results

FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn’t done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD.

Conclusions

Skin lesions appear to be more prevalent than previously reported (<30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.  相似文献   

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Introduction

Tinea capitis (TC) is a dermatophytosis that affects the hair and scalp. The epidemiology of TC depends on the different geographical areas and is variable over time. Direct microscopic examination and fungal culture are essential to confirm the diagnostic suspicion and to identify the germ involved.

Objectives

To determine the frequency of TC, to identify the etiological agents and to analyze the epidemiological aspects, in patients with suspected TC from Santiago Norte during the period 2009-2015.

Materials and methods

A total of 505 patients with suspected TC were evaluated in the Dermatology Laboratory, Hospital Clinico Universidad de Chile. Direct microscopic examination was performed with KOH 30% and fungal culture of scalp lesions. Identification of the fungi was mainly morpho-physiological.

Results

The diagnosis of TC was confirmed in 155 cases (30.7%). Male gender predominated (57.4%). The average age was 5 years. 85.2% of the cases occurred in the preschool and school population. The most frequent isolated agent was Microsporum canis in 89.8%, followed by Trichophyton tonsurans in 7.1%. It was confirmed that 81.8% of the cases of Trichophyton tonsurans had foreign ancestry, mainly of Haiti and Peru.

Conclusions

This study evidenced the occurrence of Trichophyton tonsurans as a cause of TC, which could be explained by the increase in the immigrant population and the anthropophilic characteristics of the dermatophyte.  相似文献   

5.

Introduction

Bowen's disease is a squamous cell carcinoma in situ. Its prevalence is higher in women, and mainly occurs in sun-exposed skin. It typically presents as well-demarcated scaly plaques. Multiple treatments currently exist, with the most common being surgical excision. Using several cases, this study describes the clinical and demographic characteristics of this disease in Bucaramanga, Colombia, with this being the first data reported on this condition in Latin-America.

Methods

A case series study was conducted that included patients from 2005 to 2017 with a clinical and histological diagnosis of Bowen's disease. Cases were extracted from the database of an outpatient department of a high-complexity centre in Bucaramanga, Colombia.

Results

A total of 64 cases were analysed. Women were more commonly affected than men (67.2%) with a 2:1 ratio. The most affected area was the lower extremities (34.3%), and the classic lesion was present in 92.2% of the cases, followed by pigmented lesions (6.2%). Surgical excision was performed on 57.9% of the patients, and persistence of the lesions was found in 6.2% of the cases, with all of them being treated initially with imiquimod.

Discussion

No significant differences were found in the clinical or demographic distribution or in the treatment performed compared with world literature. Nonetheless, a higher frequency of multiple lesions in atypical locations, and pigmented lesions were observed, with no identified risk factor to account for these results.  相似文献   

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Background

Cold atmospheric plasma (CAP) emerged as a novel therapeutic field with applications developed for bacterial sterilization, wound healing and cancer treatment. For clinical implementation it is important to know how CAP works and which molecular changes occur after the CAP treatment. Vascularization is an important step during wound healing, however, the effects of CAP on wound angiogenesis are not well examined so far. Furthermore, it has not been investigated, whether CAP primarily affects endothelial cells directly or via paracrine mechanisms to modulate the vasculature.

Objective

This study concentrates on the influence of CAP on angiogenesis-related molecules in human epidermal keratinocytes, dermal fibroblasts and endothelial cells.

Methods

CAP was generated by the MicroPlaSter ß® plasma torch system and CAP effects on angiogenesis were determined in vitro and in vivo.

Results

We observed that CAP significantly induces the expression of Artemin, EGF, EG-VEGF (PK1), Endothelin-1 (ET-1), FGF-2 (FGF basic), IL-8 (CXCL8) and uPA in keratinocytes and Angiogenin (ANG), Endostatin (Col18A1), MCP-1 (CCL2), MMP-9, TIMP-1, uPA and VEGF in fibroblasts. In addition, CAP activates the expression of Angiopoietin-2 (Ang-2), Angiostatin (PLG), Amphiregulin (AR), Endostatin, FGF-2 and angiogenic-involved receptor expression of FGF R1 and VEGF R1 in HUVEC endothelial cells. It was also demonstrated that supernatants collected from CAP activated fibroblasts and keratinocytes elevate tube formation by endothelial cells and FGF-2 appears to be an important pro-angiogenic factor that controls vascularization via paracrine mechanisms. Mouse experiments supplement that CAP promotes angiogenesis during wound healing in vivo.

Conclusions

Taken together, these results suggest that CAP modulates angiogenesis-involved factors via autocrine and paracrine mechanisms and may be used to affect angiogenesis during wound healing.  相似文献   

9.

Background

Tuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood.

Objective

Recently emerging evidence supports a role for autophagy in skin pigmentation. Herein, we investigated the impact of autophagic dysregulation on TSC-associated hypopigmentation.

Methods

Skin samples from 10 patients with TSC, each bearing characteristic hypopigmented macules, and 6 healthy donors were subjected to immunohistochemical and electron microscopic analyses. In addition, TSC2-knockdown (KD) was investigated in human epidermal melanocytes by melanin content examination, real-time PCR, western blotting analyses, and intracellular immunofluorescence staining.

Results

Activation of the mTOR signaling pathway decreased melanocytic pigmentation in hypopigmented macules of patients with TSC and in TSC2-KD melanocytes. In addition, LC3 expression (a marker of autophagy) and autophagosome counts increased, whereas, intracellular accumulation of autophagic degradative substrates (p62 and ubiquitinated proteins) was evident in TSC2-KD melanocytes. Furthermore, depigmentation in TSC2-KD melanocytes was accelerated by inhibiting autophagy (ATG7-KD or bafilomycin A1-pretreatment) and was completely reversed by induction of autophagy via mTOR-dependent (rapamycin) or mTOR-independent (SMER28) exposure. Finally, dysregulation of autophagy, marked by increased LC3 expression and accumulation of ubiquitinated proteins, was also observed in melanocytes of TSC-related hypopigmented macules.

Conclusion

Our data demonstrate that melanocytes of patients with TSC display autophagic dysregulation, which thereby reduced pigmentation, serving as the basis for the hypomelanotic macules characteristic of TSC.  相似文献   

10.

Background

Mechanical stress is an ubiquitous challenge of human cells with fundamental impact on cell physiology. Previous studies have shown that stretching promotes signalling cascades involved in proliferation and tissue enlargement.

Objective

The present study is dedicated to learn more about cellular structures contributing to perception and signal transmission of cell stretch. In particular, we hypothesized that desmosmal contacts and the adjacent keratin filament build an intercellular matrix providing information about the mechanical load.

Methods

Epidermal cells with different keratin equipment were seeded on flexible silicon dishes and stretched. As read out parameter the activation of PKB/Akt and p44/42 was monitored by Western blotting. Likewise desomosomal contacts were manipulated by depletion or addition of calcium. Moreover, desmoglein 3 and desmocollin 3 were blocked by either specific antibodies or siRNA.

Results

It was found that the omission of calcium from the medium, a necessary cofactor for desmosomal cadherins, inhibited stretch mediated activation of PKB/Akt and p44/42. The relevance of desmosomes in this context was further substantiated by experiments using a desmoglein 3 blocking antibody (AK23) and siRNA against desmocollin 3. Moreover, disruption of the keratin filament by sodium orthovanadate also abrogates PKB/Akt and p44/42 activation in response to stretch. Likewise, KEB-7 keratinocytes harbouring a mutation in the keratin 14 gene and genetically modified keratinocytes devoid of any keratin show an altered signalling after stretch indicating the relevance of the keratin filament in this context.

Conclusion

Besides their important role in cell architecture our results identify desmosomes and keratins as mechanosensing structures.  相似文献   

11.

Introduction

Tattooing has become a popular practice in western countries, particularly among younger populations. Tattoos, however, can cause complications, such as infections, allergic or foreign-body reactions, and even systemic inflammatory responses.

Patients and methods

We conducted a retrospective study of all patients seen for tattoo-related complications at our skin allergy unit between January 2002 and December 2016.

Results

We studied 23 patients. Nine of these experienced early complications, all related to infection. The other 14 patients developed late reactions. Ten were diagnosed with probable allergic contact dermatitis to ink, but the suspect allergen was identified in just 3 cases and confirmed in just 1 of these. There were 2 cases of cutaneous sarcoidosis, 1 case of foreign body granuloma, and 1 case of neuropathy.

Conclusions

Complications resulting from tattoos are relatively common dermatology complaints. Drawing from our experience, we propose a diagnostic algorithm designed to guide dermatologists in evaluating different reactions to tattoos and prescribing appropriate treatment.  相似文献   

12.

Introduction

Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor.

Objective

To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib.

Materials and methods

Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians’ assessment and patients’ subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible.

Results

In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months).

Conclusions

This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.  相似文献   

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Background

Atopic dermatitis (AD) is recently increasing among populations, but the underlying mechanisms remain controversial. Interactions between the gut microbiota and mucosal immunity are considered to be a crucial etiology. Fructooligosaccharide (FOS), prebiotics have been reported as activators of the gut microbiota.

Objective

The aim of this study was to investigate the effects of kestose, the smallest FOS and FOS on atopic dermatitis in mice.

Methods

An AD mouse model was developed by (ovalbumin) epidermal sensitization using BALB/c mice. Kestose (1%, 5%, and 10%) or FOS (5%, positive control) was orally administered throughout the study.

Results

In comparison with the values observed for the control AD mice, transepidermal water loss (TEWL), clinical score, and skin inflammation on histopathology were significantly decreased by the oral administration of kestose. Total IgE, thymic stromal lymphopoietin (TSLP) in skin, and IL-4 were also suppressed by this administration. In addition, the population of CD4+Foxp3+ cells in mesenteric lymph nodes (MLNs) and acetate concentrations in feces were significantly increased by kestose treatment.

Conclusions

These findings suggest that kestose activates the gut immune system to induce the tolerance against allergic skin inflammations in AD.  相似文献   

16.

Background

Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and increased T cell infiltration. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key factor that affects T cell function and immune response. However, whether the expression of CTLA-4 affects the severity of psoriasis is still unknown.

Objective

The aim of the project was to investigate the correlation between the expression of CTLA-4 and the severity of psoriasis.

Methods

The plasma soluble CTLA-4 levels and membrane CTLA-4 expression were measured by enzyme-linked immunosorbent assay and immunohistochemistry analysis in mild, moderate and severe psoriasis patients, respectively. Imiquimod-induced mouse model of psoriasis was treated with CTLA-4 immunoglobulin fusion protein (CTLA-4 Ig) or anti-CTLA-4 antibody. Epidermal thickness and infiltrating CD3+ T cell counts were evaluated.

Results

The plasma soluble CTLA-4 levels had no significant difference among mild, moderate, and severe patients (p?>?0.05). However, the membrane CTLA-4 expression in skin was significantly higher in mild psoriasis patients compared to moderate and severe psoriasis patients (17652.86?±?18095.66 vs 6901.36?±?4400.77 vs 3970.24?±?5509.15, p?<?0.001). Furthermore, in imiquimod-induced mouse model of psoriasis, the results showed that mimicking CTLA-4 function improved the skin phenotype and reduced epidermal thickness (172.87?±?28.25 vs 245.87?±?36.61?μm, n?=?6, p?<?0.01) as well as infiltrating CD3+ T cell counts (5.09?±?3.45 vs 13.45?±?4.70, p?<?0.01) compared to control group. However, blocking CTLA-4 function aggregated the skin phenotype including enhanced epidermal thickness and infiltrating CD3+ T cell counts compared to control group.

Conclusion

These results indicated that the expression of mCTLA-4 in skin lesion inversely correlated with the severity of psoriasis and CTLA-4 might play a critical role in the disease severity of psoriasis.  相似文献   

17.

Introduction

Although Mercromina Film and other topical antiseptics are widely used, they are not included in the standard series recommended by the Spanish Contact Dermatitis and Skin Allergy Research Group for testing suspected allergic contact dermatitis (ACD). Furthermore, no recent studies have investigated the allergenic potential of merbromin.

Objective

To determine the allergenic potential of merbromin and compare it with that of other topical antiseptics widely used in clinical practice, including povidone-iodine, chlorhexidine, and eosin.

Material and methods

Prospective single-center observational safety study of 105 patients with suspected ACD seen at the dermatology department of our hospital.

Results

Of the 105 patients studied, 1.9% had a positive patch test to merbromin and 12.4% were sensitized to povidone-iodine. The differences in the proportion of patients with ACD to Betadine Solución Dérmica (povidone-iodine) compared with the rest of the antiseptics was statistically significant (McNemar test, P < .05). No adverse reactions were observed in any of the patients.

Conclusions

Based on the patch tests conducted, Mercromina Film has very low allergenic potential. The highest allergenic potential was observed for povidone-iodine.  相似文献   

18.

Background

Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported.

Objective

The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis.

Methods

Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i.p.) with or without RvD1 or tert-butoxycarbonyl Met-Leu-Phe peptide (Boc), a lipoxin A4 (ALX) receptor antagonist. The severity was monitored and graded using a modified human scoring system, the Psoriasis Area and Severity Index (PASI), histopathology, and the signature cytokines of psoriasis (IL-23, IL-17, IL-22 and TNF-α). The mRNA and protein levels of inflammatory cytokines were quantified by quantitative real-time PCR (QRT-PCR) and ELISA. The expressions of signaling proteins MAPKs and NF-κB p65 were analyzed using western blotting. Electrophoretic mobility shift assay (EMSA) was used to check NF-κB p65 DNA binding activity.

Results

Our study showed that RvD1 alleviated IMQ-induced psoriasiform dermatitis and improved skin pathological changes. RvD1 markedly inhibited IMQ-induced activation of ERK1/2, p38, JNK (c-Jun N-terminal protein kinase, a subfamily of MAPKs), and NF-κB. Furthermore, pretreatment with Boc, would not exacerbate skin inflammation of IMQ-induced mice, but significantly reversed the beneficial effects of RvD1 on IMQ-induced psoriasiform inflammation.

Conclusion

RvD1 can obviously improve skin inflammation in IMQ-induced mice psoriasiform dermatitis. The protective mechanisms might be related to its selective reaction with lipoxin A4 receptor/Formyl-peptide receptor 2 (ALX/FPR2), by downregulating relevant cytokines of the IL-23/IL-17 axis expression, the inhibition of MAPKs and NF-κB signaling transduction pathways. Thus, these results show that RvD1 could be a possible candidate for psoriasis therapy.  相似文献   

19.

Background and objective

Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24 weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab.

Material and methods

The consensus document we present is the result of a series of meetings by the CSU working group of “Xarxa d’Urticària Catalana i Balear” (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon.

Results

Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7 days, the Urticaria Control Test, or both.

Conclusions

The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.  相似文献   

20.

Background

Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities.

Objective

We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology.

Methods

Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized.

Results

SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients.

Conclusion

The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc.  相似文献   

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