皮肤癣菌致病因素的研究进展

皮肤癣菌感染是人类最常见的真菌感染.皮肤癣菌专性感染角质层、指（趾）甲、毛发等部位,引起体癣、手足癣、甲癣、头癣等疾病.其致病过程主要包括黏附、侵袭.通过对各种体外模型的研究发现,皮肤癣菌的主要致病因素包括黏附相关物质、多种蛋白水解酶等,但这些物质在皮肤癣菌致病过程中所起的具体作用尚待继续研究.通过概述皮肤癣菌感染过程中出现的主要致病因素的研究进展,为进一步研究皮肤癣菌病的致病机制和临床治疗带来新的思路.     

浅部真菌病2600例病原菌分析

目的了解昆明地区浅部致病真菌的分布情况。方法对本科2010年1月-2011年6月拟诊为浅部真菌病患者的临床标本再次进行镜检和分离培养及菌种鉴定,并对结果进行统计学分析。结果 7944份临床送验标本中,直接涂片镜检阳性率29.39%,培养阳性率19.70%,而镜检和(或)培养的阳性率为32.73%,显著高于单一的镜检或培养。上述3种方法的真菌检出率差异均有统计学意义(P均<0.005)。分离的1565株浅部致病真菌中,红色毛癣菌1088株(69.52%),马拉色菌216株(13.80%),须癣毛癣菌118株(7.54%)。镜检和(或)培养阳性的2600例浅部真菌病患者中,足癣803例(30.88%),甲真菌病424例(16.31%),股癣386例(14.85%),体癣364例(14.00%),花斑癣259例(9.96%),手癣194例(7.46%),马拉色菌毛囊炎83例(3.19%)和头癣46例(1.77%),同时患有手癣和足癣41例(1.58%)。结论镜检结合培养法的阳性率显著高于单一镜检或培养法,昆明地区浅部真菌的病种以足癣、甲真菌病、股癣较多见,浅部致病真菌以红色毛癣菌和马拉色菌为主。     

共聚焦激光扫描显微镜在皮肤浅部真菌感染诊断中应用价值的评估

目的 探讨皮肤共聚焦激光扫描显微镜（CLSM）在常见浅部真菌感染诊断中的应用价值。 方法 根据临床病史及体征初步诊断为浅部真菌感染患者59例,选定3处典型皮损做CLSM检查,记录各项指标的扫描结果,再行真菌镜检。结果 CLSM检测的25例手足癣患者中,14例（56%）角质层内可见菌丝,真菌镜检均阳性;11例角质层内未发现菌丝,真菌镜检8例阳性;新皮损（＜ 3周） 共8例,CLSM阳性7例,真菌镜检均阳性;旧皮损（＞ 3周）共17例,CLSM阳性7例（41%）,真菌镜检阳性14例（82%）。在检测的24例股癣患者中,19例（79.17%）角质层内可见菌丝,真菌镜检均阳性;5例角质层内未发现菌丝,真菌镜检4例阳性;新皮损（＜ 3周） 共17例,CLSM阳性16例（94.12%）,真菌镜检均阳性;旧皮损（＞ 3周）共7例,CLSM阳性3例,真菌镜检阳性6例。在检测的10例花斑糠疹患者中,CLSM均未发现菌丝,而真菌镜检阳性8例。外用联苯苄唑乳膏2周后的10例手足癣、股癣患者,CLSM检查均未见菌丝,角质层完整,真菌镜检阴性。结论 CLSM在手足癣、股癣的新发皮损的检查上与真菌镜检具有较高的一致性,在临床诊断上有一定的应用价值。     

Butenafine: an update of its use in superficial mycoses

Butenafine is a synthetic benzylamine antifungal agent that may be fungicidal against susceptible organisms, e.g., dermatophytes. Butenafine may be effective and safe in the treatment of interdigital tinea pedis (apply twice daily for 1 week or once daily for 4 weeks), tinea corporis/tinea cruris (apply twice daily for 2 weeks), and pityriasis versicolor (apply once daily for 2 weeks). The effectiveness of the drug persists for at least 4 weeks following the discontinuation of therapy suggesting that there is some retention of the drug in the skin following termination of active therapy.     

Optimal Management of Fungal Infections of the Skin, Hair, and Nails

Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.     

Defective barrier function in melasma skin

Background Melasma is characterized by increased pigmentation and photodamaged features, which include solar elastosis. Recently, we detected the downregulation of the genes most associated with lipid metabolism using microarray analysis in melasma. These findings suggested that lesional skin may have different biophysical characteristics, and, in particular, an altered skin barrier function. Objective To determine the cutaneous biophysical characteristics of melasma. Methods The melanin index, erythema index, stratum corneum hydration, sebum content and transepidermal water loss (TEWL) were measured for lesional and perilesional normal skin of 16 melasma patients and then compared. In addition, a skin biopsy was performed on 11 of the 16 study subjects to measure stratum corneum thickness and to study the protein expressions of PPAR‐α and ALOX15B. Results Melanin index, erythema index and stratum corneum hydration were significantly higher in lesional skin than in perilesional normal skin. No significant difference was found between lesional and normal skin in terms of basal TEWL level or sebum content. However, the rate of TEWL after barrier perturbation was significantly higher for lesional skin, and the barrier recovery rate was significantly delayed. Furthermore, a trend towards thinned stratum corneum was observed for lesional skin, and this was correlated with barrier recovery rate. The expressions of PPAR‐α and ALOX15B were variable in the samples. Conclusions Melasma skin is characterized by impaired stratum corneum integrity and a delayed barrier recovery rate.     

Phenotypic characterization in situ of inflammatory cells in pityriasis (tinea) versicolor

The cellular response in pityriasis (tinea) versicolor lesions was analysed in situ with an immunohistochemical double staining technique combined with periodic acid-Schiff staining in frozen sections of skin biopsies from 9 patients. The proportions of B and T cells and subpopulations of T cells in the blood were normal as were the proliferative responses of blood mononuclear cells against various B- and T-cell mitogens and antigens. Fungi were observed in stratum corneum in all lesions, and there were moderate cell infiltrates in both epidermis and dermis as compared to biopsies from normal-looking skin. The majority of the infiltrating perivascular cells reacted with anti-Leu 1 antibodies (all mature peripheral T cells). Anti-Leu 2a reactive cells ('suppressor/cytotoxic' phenotype) were few and scattered, whereas anti-Leu 3a reactive cells ('helper/inducer' phenotype) dominated. This investigation demonstrates that pityriasis versicolor is not a simple overgrowth of the fungus in stratum corneum, but is accompanied by infiltrating immunocompetent cells in both epidermis and dermis.     

Barrier function, epidermal differentiation, and human beta-defensin 2 expression in tinea corporis

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-beta-defensin 2 (hBD-2) protein expression in 10 patients with tinea corporis caused by Trichophyton rubrum (T. rubrum). We found disturbed skin barrier function as shown by a significant increase in transepidermal water loss (TEWL) and specific ultrastructural changes including disturbed formation of extracellular lipid bilayers, lamellar body extrusion, and deposit of clotted material at the stratum granulosum/stratum corneum interface. Epidermal proliferation in tinea increased several fold and accordingly, proliferation and inflammation-associated keratins K6, K16, and K17 were expressed. Expression of basal keratins K5 and K14 increased, whereas differentiation-associated K10 was reduced. Reduction of the cornified envelope proteins involucrin, loricrin, and the S100 protein filaggrin was also seen. Reduced filaggrin expression correlated with reduced skin hydration; protein breakdown products of filaggrin have been shown to be important for water binding. Surprisingly, we found pronounced epidermal protein expression of hBD-2, which may be related to disturbed epidermal differentiation and inflammation. hBD-2 showed a weak, although significant, antifungal activity against T. rubrum in the turbidimetric assay and the immunohistological staining was somewhat less pronounced in areas directly underneath fungal hyphae in the stratum corneum. Together, we describe profound changes in skin barrier structure and function, epidermal proliferation, and differentiation including pronounced protein expression of hBD-2 in tinea corporis.     

Wood灯在皮肤浅表真菌感染诊断中应用价值评估

目的 评估Wood灯在皮肤常见浅表真菌感染诊断中的应用价值.方法 对129例根据临床病史及体征初步诊断为皮肤浅表真菌感染患者进行Wood灯和真菌实验室检查.结果 花斑糠疹、马拉色菌毛囊炎患者Wood灯检查的阳性率分别为84%、85.7%,同时阳性病例的真菌培养或镜检的阳性率达92.9%、87.5%,两者有高度的一致性.而临床诊断手足癣和体股癣者其荧光阳性率只有8.3%.真菌总检出率却高达85.4%(41/48),两者不具有一致性.结论 Wood灯在花斑糠疹、马拉色菌毛囊炎的检查上有较高的特异性和敏感性,临床诊断上有应用价值,而对手足癣和体股癣诊断则无意义.

Abstract：

Objective To estimate the performance of Wood's lamp examination in the diagnosis of superficial cutaneous fungal infections. Methods Totally, 129 patients, who were diagnosed with superficial cutaneous fungal infections according to clinical medical history and signs, were enrolled in this study. Wood's lamp examination of lesions was carried out. Cutaneous samples were obtained from the patients and subjected to microscopic examination and fungal culture. Results Wood's lamp examination was positive in 84% and 85.7% of patients with tinea versicolor and malassezia folliculitis, respectively; among these patients positive for Wood's lamp examination, 92.9% were positive for fungal culture, and 87.5% for microscopic examination. In patients clinically diagnosed with tinea manus and pedis, tinea corporis or tinea cruris, 8.3% were positive for Wood's lamp examination, while 85.4% were positive for fungal examination. There was a high consistency between Wood's lamp examination and fungal examination in patients with tinea versicolor and malassezia folliculitis, but not in those with tinea manus and pedis, tinea corporis or tinea cruris. Conclusions Wood's lamp examination shows a high specificity and sensitivity and is useful in the diagnosis of tinea versicolor and malassezia folliculitis, but seems unapplicable for the diagnosis of tinea manus and pedis, tinea corporis or tinea cruris.     

【开放获取】皮肤干燥是通透屏障功能受损的表现吗？

【摘要】 有学者认为,皮肤干燥是表皮通透屏障功能受损的表现,但目前尚没有足够的证据证明这一观点。实际上,皮肤干燥是角质层含水量降低的表现。角质层含水量主要由角质层天然保湿因子的量决定,而表皮通透屏障功能则主要由角质层脂质的质和量以及结构蛋白决定。如果皮肤干燥是由表皮通透屏障功能降低所致,那么,角质层含水量应当与透皮失水率呈负相关性。但是研究表明,无论是正常人皮肤、鱼鳞病皮损或皮脂腺缺乏的小鼠皮肤,角质层含水量与透皮失水率均无负相关性。相反,有研究显示,人角质层含水量与透皮失水率呈正相关性。因此,皮肤干燥似乎不是表皮通透屏障功能受损的表现。     

Tinea versicolor in dark‐skinned individuals

In this article, we review the salient features of tinea versicolor and describe the epidemiology, clinical presentation, and histopathology of this mycosis in dark‐skinned individuals. Tinea versicolor is caused by an overgrowth of the Malassezia genus. It manifests clinically as asymptomatic hypopigmented macules, hyperpigmented macules, or a combination of the two. Under light microscopy, Malassezia presents as a dimorphic fungus – in both the hyphal and yeast form. Most clinicians have found that the majority of dark‐skinned patients present solely with hypopigmented lesions. Under light microscopy, lesions on dark skin involved with tinea versicolor tend to have a thicker stratum corneum, more tonofilaments in the granulosum, and more sequestered melanosomes. Differential diagnosis includes confluent and reticulated papillomatosis, seborrheic dermatitis, pityriasis rosea, pityriasis alba, and vitiligo. Tinea versicolor can be successfully managed in most cases with topical antifungal treatments. Cases of recurrence, such as those seen in immunocompromised patients, may necessitate scheduled oral or topical therapy.     

Depth profiling of stratum corneum biophysical and molecular properties

Background The barrier function of the skin may be characterized by a number of biophysical and molecular methods. Variation in the barrier properties as a function of depth has not been explored in detail. Objectives To characterize changes in corneocyte surface area, corneocyte maturity, selected protease activities and transepidermal water loss (TEWL) in the ventral forearm with increasing depth. Methods The left mid‐ventral forearm of 22 healthy volunteers was selected as the study site. After tape stripping, corneocyte maturity and surface area were assessed. The protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and inflammatory tryptase was measured using a fluorogenic probe assay. Protein content and TEWL were also recorded. Results Corneocyte maturity and surface area decreased with increasing number of tape strippings, i.e. depth into the skin. More mature corneocytes were typically larger than less mature corneocytes. The protease activities of both the desquamatory and inflammatory enzymes together with the protein content were highest in the outer layers of the stratum corneum and decreased with depth. As expected, TEWL increased as more stratum corneum layers were removed. There were no statistical differences between men and women or caucasian and black subjects for all of the parameters studied. Conclusions The techniques used in this study provide rapid noninvasive measures of the spatial distribution of corneocyte maturity and surface area as well as protease activity and protein content within different levels of the stratum corneum layers. The methods used will allow mechanistic insight into the effects of formulation excipients and active ingredients on epidermal turnover and skin barrier function.     

Clinical and mycological status of the Trichophyton mentagrophytes (interdigitale) syndrome of chronic dermatophytosis of the skin and nails

The syndrome of tinea pedis caused by human-adapted Trichophyton mentagrophytes (interdigitale) can be recognized by two signs not characteristically seen in tinea pedis caused by T. rubrum and Epidermophyton floccosum:1 bullous > 2 mm vesicles in the thin skin of the plantar arch and along the sides of the feet and heel adjacent to the thick plantar stratum corneum,2 and white superficial onychomycosis. The relationship of the syndrome to zoophilic T. mentagrophytes remains in question.     

Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation

BACKGROUND: UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. OBJECTIVE: The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. METHODS: Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. RESULTS: The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. CONCLUSION: The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.     

Functions of the stratum corneum in systemic sclerosis as distinct from hypertrophic scar and keloid functions

Both transepidermal water loss (TEWL) and skin surface high-frequency conductance are functions of the skin barrier. Systemic sclerosis (SSc) and hypertrophic scar (HS)/keloid are characterized by abnormal fibrotic changes in the dermis. Since the close interrelationship between the epidermis and the dermis has been well established, we analyzed the stratum corneum functions of forearm skin in 39 SSc patients after assessing the degree of the skin thickening and compared those functions with 10 age-matched normal controls. We also analyzed the stratum corneum functions of HS or keloid lesions in seven patients using the same methods, and compared those functions to adjacent or contralateral normal skin in identical patients. Neither the TEWL, nor high-frequency conductance of forearm skin in SSc patients were significantly different from those in normal controls. There was no correlation between the levels of TEWL or high-frequency conductance and the degree of skin thickening in SSc. In HS or keloid conditions, high-frequency conductance was significantly elevated (42.5+/-8.9 vs. 26.4+/-5.7, P<0.001). Although TEWL was elevated, there was no statistical significance (48.6+/-39.7 vs. 25.1+/-10.1). Our results revealed that stratum corneum functions are distinct between SSc and HS or keloid. This may reflect the various natures of dermal changes, which in turn differentiate the functions of the stratum corneum in the diseases.     

Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation

Sodium lauryl sulfate (SLS), a surfactant frequently used in the induction of experimental irritant contact dermatitis in animals and in humans, characterstically induces a dose-related increase in TEWL (transepidermal water loss). Ceramides are considered to be important in the regulation of the skin barrier. We therefore examined the relationship between initial ceramide content of stratum corneum and induced changes in skin color (erythema) and barrier function, after SLS application under occlusion (1% and 3% in water) to the forearm of 14 volunteers. Stratum corneum sheets were removed, stratum corneum lipids extracted, and ceramide composition determined from chromatograms (TLC) using densitometry. After determining baseline skin color and TEWL at each area. 2 samples of stratum corneum were obtained from each volunteer. Clinical and instrumental controls of the SLS-induced irritation were performed at 24, 48, 72 and 96 h. Erythema was evaluated by colorimetry; barrier impairment by changes in TEWL. We found inverse correlations between baseline ceramide 61 (weight) and the 24 h erythema score for SLS: between ceramide I and 24 h TEWL, and between ceramide 611 and 72 h TEWL for SLS 3%. Our findings suggest that low levels of these ceramides may determine a proclivity to SLS-induced irritant contact dermatitis.     

Defective barrier function accompanied by structural changes of psoriatic stratum corneum

Although barrier function of psoriatic skin is shown to be decreased by measuring transepidermal water loss (TEWL), few reports exist examining other physical skin properties and components including stratum corneum hydration, natural moisturizing factor (NMF), free fatty acids (FFA), β‐sheet and α‐helix ratio of structural protein(s), and sebum content. We compared the skin properties and components of normal, involved and uninvolved skin of psoriasis. Using a corneometer and attenuated total reflection‐infrared spectrometer, we measured TEWL, stratum corneum hydration, NMF, FFA, β/α ratio and sebum in psoriasis vulgaris patients and healthy controls. TEWL and β/α ratio of involved psoriatic skin were significantly increased compared with uninvolved skin and normal control skin. In contrast, stratum corneum hydration , NMF and FFA, but not sebum, are significantly decreased in the involved skin compared with uninvolved skin and normal skin. TEWL and stratum corneum hydration returned to the normal levels following clinical improvement of the lesion. Barrier function and hydration of psoriatic skin are defective and secondary structure in stratum corneum protein is altered in the involved psoriatic skin.     

Skin Characteristics in Patients with Pityriasis Versicolor Using Non-Invasive Method, MPA5

Background

Skin pigmentary changes of pityriasis versicolor may occur as either hyperpigmented or hypopigmented lesions, depending on the outcome of interactions between Malassezia yeasts and the skin, such as lipoperoxidation process, stimulus of inflammatory cell to melanocytes, and increased thickness of keratin layer.

Objective

To investigate skin characteristic factors that enhance the susceptibility to Malassezia yeasts and provoke different color changes of pityriasis versicolor patients.

Methods

To clarify these factors, we investigated the skin characteristics of pityriasis versicolor patients, using a non-invasive method known as MPA 5® (Courage and Khazaka, Germany). A total of 90 normal healthy subjects and 30 pityriasis versicolor patients were included in this study.

Results

Both hyperpigmented and hypopigmented pityriasis versicolor skin lesions showed higher humidity, increased sebum excretion rate and increased transepidermal water loss (TEWL) values than normal healthy subjects. But no significant difference of specific Malassezia yeasts species between hyperpigmented and hypopigmented skin lesions was evident.

Conclusion

These results indicate that higher humidity and increased sebum level provide a better growing environment of Malassezia yeasts in the skin, leading to the assumption that interaction between Malassezia yeasts and skin barrier materials makes disruption of skin barrier causing increased TEWL.     

Ciclopirox for the treatment of superficial fungal infections: a review

Ciclopirox is a broad-spectrum antifungal agent that also exhibits anti-inflammatory and antibacterial activity. The lotion and cream formulations of ciclopirox are effective in many types of infection, including tinea corporis/cruris, tinea pedis, cutaneous candidiasis, pityriasis (tinea) versicolor, and seborrheic dermatitis. The new ciclopirox gel 0.77% formulation is also indicated for the treatment of seborrheic dermatitis of the scalp, interdigital tinea pedis and tinea corporis.     

Mycology – an update. Part 1: Dermatomycoses: Causative agents,epidemiology and pathogenesis

Dermatomycoses are caused most commonly by dermatophytes. The anthropophilic dermatophyte Trichophyton rubrum is still the most frequent causative agent worldwide. Keratinolytic enzymes, e.g. hydrolases and keratinases, are important virulence factors of T. rubrum. Recently, the cysteine dioxygenase was found as new virulence factor. Predisposing host factors play a similarly important role for the development of dermatophytosis of the skin and nails. Chronic venous insufficiency, diabetes mellitus, disorders of cellular immunity, and genetic predisposition should be considered as risk factors for onychomycosis. A new alarming trend is the increasing number of cases of onychomycosis – mostly due to T. rubrum – in infancy. In Germany, tinea capitis is mostly caused by zoophilic dermatophytes, in particular Microsporum canis. New zoophilic fungi, primarily Trichophyton species of Arthroderma benhamiae, should be taken into differential diagnostic considerations of tinea capitis, tinea faciei, and tinea corporis. Source of infection are small household pets, particularly rodents, like guinea pigs. Anthropophilic dermatophytes may be introduced by families which immigrate from Africa or Asia to Europe. The anthropophilic dermatophytes T. violaceum, T. tonsurans (infections occurring in fighting sports clubs as “tinea gladiatorum capitis et corporis”) and M. audouinii are causing outbreaks of small epidemics of tinea corporis and tinea capitis in kindergartens and schools. Superficial infections of the skin and mucous membranes due to yeasts are caused by Candida species. Also common are infections due to the lipophilic yeast fungus Malassezia. Today, within the genus Malassezia more than 10 different species are known. Malassezia globosa seems to play the crucial role in pityriasis versicolor. Molds (also designated non‐dermatophyte molds, NDM) are increasingly found as causative agents in onychomycosis. Besides Scopulariopsis brevicaulis, several species of Fusarium and Aspergillus are found.