基于脂质组学的新生儿痤疮面部皮损脂质分析

【摘要】 目的 分析新生儿痤疮皮损和健康婴儿面部正常皮肤表面脂质（SSL）的差异。方法 2018年6 - 8月在首都儿科研究所附属儿童医院皮肤科收集36例新生儿痤疮（痤疮组）面部皮损及 36例健康婴儿（对照组）面部皮肤脂质标本。采用超高效液相色谱-四极杆飞行时间质谱联用技术得到脂质图谱,用多元数据分析方法得到脂质成分的具体信息。采用SPSS19.0软件进行独立样本t检验分析两组间差异。结果 与对照组相比,痤疮组患儿面部皮肤甘油脂类和孕烯醇酮脂类显著增加（均P < 0.001 ）,但脂肪酸类、甘油磷脂类、鞘脂类、固醇脂类、糖脂类、多聚乙烯类显著下降（P < 0.01或0.05）。进一步分析显示,痤疮组脂质总量、甘油二酯、蜡酯 、角鲨烯平均相对含量均高于对照组（P < 0.001或0.05）,但亚油酸平均相对含量低于对照组（P < 0.001）。结论 新生儿痤疮面部皮损脂质总量较健康婴儿明显增加,脂质成分也存在明显差异。     

The effect of testosterone and anabolic steroids on the skin surface lipids and the population of Propionibacteria acnes in young postpubertal men

The effect of testosterone and anabolic steroids on skin surface lipids and the population of Propionibacteria acnes (P. acnes) was studied in power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 12-week strength training period. After 8 weeks' use of hormones the amount of dissolved skin surface lipids (SSL), and the Colony Forming Units/cm2 (CFU/cm2) of P. acnes had increased (p less than 0.01). The percentage values of dissolved SSL constituents changed. The cholesterol (CHO) and also the relative values of free fatty acids (FFA) increased. SSL constituents obtained by collection on absorbent paper likewise changed the dissolved constituents. It was concluded that high doses of testosterone and anabolic steroids may increase the SSL, the P. acnes population, and the percentage of the CHO and FFA of the skin surface lipids in healthy young men.     

Effect of a single overnight topical application of miconazole nitrate paste on acne papules

BACKGROUND: The classical management of acne calls for prolonged oral and/or topical treatments; however, some patients request a rapid effect to make the papules disappear within a few hours or days. OBJECTIVE: To test the effect of a single overnight application of a paste containing 0.25% miconazole nitrate on acne papules, and comparison with the effect of the same but unmedicated paste. METHOD: Narrow-band reflectance spectroscopy was used to assess the changes in E index (erythema) after overnight application of the pastes. In the first study, a total of 117 acne papules were assessed in 15 adolescents. Measurements of the E index were performed at 24-h intervals for 4 days on acne papules and the surrounding normal-looking skin. The last two assessments were performed the mornings preceding and following, respectively, a single application of the medicated paste. The second part of the study consisted of a double-blind, split-face study on 25 adolescents with acne. They applied each of the two formulations on a randomized part of the forehead. A total of 161 acne papules received the medicated paste and 160 received the same but unmedicated paste. Measurements were performed the mornings before and after the overnight treatment. RESULTS: In the first part of the study, no significant daily difference was observed between the three series of pretreatment E indices, on both acne papules and normal skin. The treatment did not affect the E index of normal skin. By contrast, it decreased significantly the E index of the acne papules. The second part of the study also showed that the medicated paste significantly decreased the E index of acne papules. This effect was significantly (P < 0.05) superior to that of the unmedicated paste. CONCLUSION: A single overnight application of miconazole nitrate paste appears to reduce the erythematous aspect of acne papules.     

The cutaneous microflora of adolescent, persistent and late-onset acne patients does not differ

The cutaneous microbiology and antibody status to Propionibacterium acnes of patients with persistent (males, n = 32; females, n = 33) and late-onset (females, n = 25) acne were compared with individuals with adolescent acne (males, n = 22; females, n = 18) and normal control volunteers (persistent acne: males, n = 26; females, n = 30; late-onset: females, n = 20). Males had significantly higher grades of acne compared with females (P < 0.05). The microflora consisted in the main of propionibacteria, staphylococci and Malassezia; other bacteria represented less than 0.01% of the total microflora. At all sites for all samples there were significantly more propionibacteria than staphylococci or Malassezia (P < 0.05). There were significantly higher (P < 0.05) numbers of microorganisms in follicular casts from patients compared with their control volunteers for female facial skin and male back skin. Twenty-six papules and 48 normal follicles were analysed. A bimodal distribution of microbial colonization was noted, with about 90% of normal follicles and about 10% of acne follicles having no detectable viable microorganisms. Anti-P. acnes IgG antibody titres were measured using a secondary fluorescein isothiocyanate antibody technique, and no significant differences in titre were found between any groups of patients (P > 0.05). Correlation analysis showed no association between the population densities of P. acnes and anti-P. acnes IgG titres. There were no differences in the microbiology of skin of adolescent acne patients, persistent acne patients or late-onset acne patients which could account for these various forms of acne.     

Fatty acids of acylceramides from comedones and from the skin surface of acne patients and control subjects

Comedonal lipids and skin surface lipids were collected from six acne patients and surface lipids were collected from sex- and age-matched controls without acne. Six series of ceramides were found in each sample, the relative amounts of which were determined by thin-layer chromatography/photodensitometry. Acylceramides (ceramide 1) were isolated by preparative thin-layer chromatography and their ester-linked fatty acids were analyzed by gas-liquid chromatography. The comedonal acylceramides contained higher proportions of 16:0, 16:1 delta 6, and 18:1 delta 6 + delta 8 and much less linoleate (18:2 delta 9,12) than the acylceramides from the skin surface. In the surface lipids from legs, acylceramides from the acne patients contained less linoleate than the acylceramides from control subjects. Free fatty acids from the comedones were also isolated and analyzed, and had a composition very similar to the esterified fatty acids of comedonal acylceramides. The results confirm that fatty acids derived from sebum become incorporated into comedonal acylceramides, displacing linoleate, and show that this process even affects the acylceramides of surface epidermis, more so in acne patients than in normal subjects.     

A possible role for squalene in the pathogenesis of acne. II. In vivo study of squalene oxides in skin surface and intra-comedonal lipids of acne patients

Skin surface lipids and lipids from open and closed comedones in acne patients were analysed by thin layer chromatography. The results showed that these lipids were enriched in polar lipids, as compared with the skin surface lipids obtained from controls without acne. In both open and closed comedones, these polar lipids appeared to be derived mainly from the oxidation of squalene, which is in agreement with our previous in vitro results. We suggest that squalene oxidation is the link between comedogenesis and bacterial colonization, and based on this, we propose a hypothesis of the pathogenesis of acne.     

The effect of marked inhibition of sebum production with 13cis-retinoic acid on skin surface lipid composition

Sebum production and skin surface lipid composition have been measured during the oral treatment with 13cis-retinoic acid of a group of patients with severe cystic acne. Two hundred and thirty-eight paired samples have been analyzed and compared. A marked, drug-induced decrease in sebum production was accompanied by a decrease in the concentration of wax esters, a slight decrease in the squalene concentration and in increase in the cholesterol concentration in the skin surface lipids. These changes were consonant with changes in the relative contributions of sebum and epidermal lipid to the surface film, except that at very low levels of sebum production there might be preferential preservation of squalene synthesis.     

Topical cimetidine treatment of acne

We present first results of topically applied cimetidine in acne. Ten patients suffering from papulopustular and comedone acne administered 2% cimetidine in indifferent lotion on their face twice a day. Clinical controls were performed every two weeks; sebum was monthly determined. After treatment of 13 weeks on the average, the clinical success was generally good. Comedones responded best, followed by papules. Pustules were hardly reduced. There was no significant reduction of SER and the lipid fractions at the end of treatment. Low concentration or insufficient penetration might be possible explanations. The efficient reduction of comedones might be an antiandrogenic effect due to modulation of the keratinization in the follicle excretory duct. Immune-modulatory effects of cimetidine and effects on the skin vessels are other possible explanations for the clinical efficacy of topical application of cimetidine in acne.     

Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy

Background  There remains the need for more effective therapeutic options to treat acne vulgaris. Interest in light-based acne treatments has increased, but few randomized, controlled clinical trials assessing the value of photodynamic therapy (PDT) for acne have been reported.
Aims  We sought to examine the efficacy of PDT using 5-aminolevulinic acid (ALA) and pulsed dye laser therapy in the treatment of acne.
Patients/methods  We conducted a randomized, controlled, split-face, single-blind clinical trial of 44 patients with facial acne. Patients were randomized to receive three pulsed dye laser treatments to one side of the face after a 60–90 min ALA application time, while the contralateral side remained untreated and served as a control. Serial blinded lesion counts and global acne severity ratings were performed.
Results  Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin. Erythematous macules (remnants of previously active inflammatory lesions) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin. There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion. Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts, while only 7% of patients responded in terms of noninflammatory lesion counts.
Conclusions  PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne.     

The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients

An important feature of atopic eczema (AE) is a decreased skin barrier function. The stratum corneum (SC) lipids – comprised of ceramides (CERs), free fatty acids (FFAs) and cholesterol – fulfil a predominant role in the skin barrier function. In this clinical study, the carbon chain length distribution of SC lipids (FFAs and CERs) and their importance for the lipid organization and skin barrier function were examined in AE patients and compared with control subjects. A reduction in FFA chain length and an increase in unsaturated FFAs are observed in non‐lesional and lesional SC of AE patients. The reduction in FFA chain length associates with a reduced CER chain length, suggesting a common synthetic pathway. The lipid chain length reduction correlates with a less dense lipid organization and a decreased skin barrier function. All changes are more pronounced in lesional SC compared with non‐lesional skin. No association was observed between lipid properties and filaggrin mutations, an important predisposing factor for developing AE. The results of this study demonstrate an altered SC lipid composition and signify the importance of these changes (specifically regarding the CER and FFA chain lengths) for the impaired skin barrier function in AE. This provides insights into epidermal lipid metabolism as well as new opportunities for skin barrier repair.     

Skin capacitance imaging of acne lesions

BACKGROUND: Little information is available about specific functional characteristics of skin in acneic patients. OBJECTIVE: To determine a capacitance mapping of lesional skin in acne in order to predict drug affinity according to the hydrophilic-lipophilic characteristics. METHOD: Skin capacitance imaging based on silicon image sensor technology was used with the SkinChip device. RESULTS: The non-optical images obtained by this means clearly identified low capacitance comedones contrasting with a perifollicular rim of high capacitance in inflammatory papules. This method also showed sweating and the follicular pores distributed in a pinpoint pattern. CONCLUSION: The objective mapping of skin surface capacitance showed large differences between acne lesions and the surrounding skin. The low capacitance of comedones contrasted with the high capacitance of the perifollicular area in inflammatory papules. These electrometric characteristics reflecting the corneocyte hydration may influence drug affinity to acne lesions.     

Different cutaneous innate immunity profiles in acne patients with and without atrophic scars

Background

Acne is a chronic inflammatory disease associated with scar development in many patients.

Objectives

To check whether early inflammatory events in the epidermis via keratinocytes influence the development of scars in acne patients.

Methods

We investigated several immunological markers involved in epidermal innate immunity in both clinically normal skin and inflammatory early papules in acne patients prone to scars or not.

Results

In normal skin of acne patients prone to scars vs not prone to scars, TLR-4, IL-2, IL-10, TIMP-2 and JUN were significantly overexpressed and the MMP-9 protein level was decreased. Similar results were obtained in early inflammatory papules (no more than three days), except for TLR-4.

Conclusion

These results suggest for the first time a link between the early events of inflammation with levels of activation of innate immunity in normal epidermis of acne patients and the development of scars. These markers could be a target for drugs in the field of scar prevention.

     

泛发型环状肉芽肿2例

环状肉芽肿是以环状丘疹或结节性损害为特征的慢性皮肤病,其中泛发型环状肉芽肿临床较少见。本文报道2例女性泛发型环状肉芽肿病例,皮损表现为躯干四肢弥漫的丘疹、环状斑块。甲状腺功能、EB病毒及巨细胞病毒抗体、血糖血脂检查均未见异常。组织病理表现为真皮浅中层栅栏样肉芽肿形成,中央结缔组织变性,周围上皮样细胞,多核巨细胞及淋巴组织细胞浸润。     

Inflammatory events are involved in acne lesion initiation

The earliest subclinical acne "lesion" is a microcomedone, of which hyperproliferation of the follicular epithelium is a characteristic feature. Inflammatory cells have been observed at the periphery of these "lesions". This study investigated whether inflammatory events occur pre or post hyperproliferative changes. Cellular, vascular, and proliferative markers were examined by immunohistochemical techniques on biopsies of clinically normal follicles from uninvolved skin and early inflamed lesions from acne patients. Control follicles were obtained from non-acne subjects. Follicles from uninvolved skin exhibited no microcomedonal features. Proliferation in the epithelium was comparable to controls and was significantly lower than in inflamed lesions. Numbers of CD3+, CD4+ T cells were elevated in the perifollicular and papillary dermis although levels were not equivalent to those in papules. The number of macrophages was also greatly increased and similar to those in papules. There were no changes in blood vessel numbers or vascular intercellular adhesion molecule 1 expression but E-selectin expression was increased to levels found in papules and vascular adhesion molecule 1 levels were upregulated. Levels of the pro-inflammatory cytokine interleukin-1 were also upregulated perifollicularly. Moreover, aberrant integrin expression was demonstrated in the epidermis around these uninvolved follicles and inflamed lesions whereas the basement membrane was still intact. These results provide novel evidence for vascular endothelial cell activation and involvement of inflammatory responses in the very earliest stages of acne lesion development.     

Acne vulgaris: proliferative cells in sebaceous glands

The proliferative activity of sebaceous glands of uninvolved skin from acne patients was analysed by means of ³H-thymidine autoradiography and by planimetry. Twelve specimens of normal skin from the back (with thirty-five glands) and two specimens from the face (with six glands) were analysed. Labelling indices and planimetric values were determined separately for the two portions within each gland: the differentiating cell pool with germinative cells and large lipid cells; and the undiffer-entiated cell pool with multilayered cells. The germinative cells of the differentiating cell pool on the back and face of patients with acne showed a significantly greater labelling index than in control subjects. The undifferentiated cell pool, although having a higher labelling index than the differentiating cell pool, was similar both in acne patients and in controls. Planimetry confirmed that the sebaceous glands of patients are much larger than those of normal subjects. Therefore, the known increase in sebum excretion in acne patients is a result of two factors—an increase in lipid cell production and an increase in sebaceous gland size.     

GLYCOSAMINOGLYCAN IN THE SKIN AND URINE OF A HUNTER SYNDROME PATIENT WITH A SPECIFIC SKIN LESION

The glycosaminoglycan (GAG) contents of the cutaneous papules, the non-eruptive skin, and the urine of a patient with Hunter syndrome were examined. Both skin samples contained hyaluronic acid (HA) and dermatan sulfate (DS) as major components and heparan sulfate (HS) and chondroitin sulfate (CS) as minor components. The HA content of the papules was greatly increased, while that of the non-eruptive skin was normal. The amounts of DS and HS were increased in all three samples; the papules, non-eruptive skin, and urine. HS from the patient's skin and urine had an electrophoretic mobility different from that of authentic HS. It seemed interesting from a pathogenetic viewpoint that the components of GAG in the cutaneous papules differed from those in the non-eruptive skin and urine.     

Clinical evidence of the endocrinological influence of a triphasic oral contraceptive containing norgestimate and ethinyl estradiol in treating women with acne vulgaris. A pilot study

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol in the treatment of women with acne vulgaris. METHODS: 12 female patients were included and 10 completed the trial. Over a period of 6 months, efficacy was assessed by means of facial acne lesion counts, by an investigator's global assessment, by patients' self-assessments and by measuring epidermal moisture and skin surface lipids. In addition, a photo documentation was compiled and hormone levels were measured. RESULTS: After 6 months of therapy, the number of acne counts improved. The success of treatment was rated positively both by the investigator and by all patients but one who did not report any changes. Skin surface lipids were significantly reduced while skin hydration showed no significant change. Testosterone and progesterone decreased, and sex-hormone-binding globulin increased, significantly. CONCLUSION: Our data show that an OC containing norgestimate and ethinyl estradiol is a good therapeutic option for women of fertile age suffering from mild to moderate acne vulgaris.     

Eosinophilic pustular folliculitis. Studies on possible chemotactic factors involved in the formation of pustules

Eosinophilic pustular folliculitis (EPF) is a dermatosis of unknown aetiology, characterized by repeated development of pruritic follicular papulopustules with a tendency to form an annular configuration on the face and other seborrhoeic areas, and by palmoplantar pustular lesions in one-fifth of the patients. Both types of lesions are infiltrated mainly by eosinophils with some polymorphonuclear leukocytes (PMN). To elucidate the mechanisms underlying pustule formation, we studied the chemotactic activity for leukocytes of the skin surface lipids (SSL) obtained from seborrhoeic areas. No specific chemotactic activity was detectable in stored SSL from patients with EPF. However, fresh SSL collected from the seborrhoeic areas of normal adults contained chemotactic substances for eosinophils and PMN which were labile on storage in air. In stratum corneum extracts from palmoplantar lesions of patients with EPF we demonstrated the presence of a 13000 molecular weight chemoattractant factor for PMN, the activity of which was partially inhibited by antiserum against C5a, and a low molecular weight lipid-soluble chemotactic factor for eosinophils, the activity of which was also lost on storage in air. Our findings suggest that these chemotactic factors play a role in the production of the characteristic pustular lesions of EPF.     

胶原贴敷料对面部轻度痤疮的屏障功能作用观察

目的评价胶原贴敷料对面部轻度痤疮患者面部屏障功能的作用,同时观察痤疮皮损、炎症后色素沉着的变化。方法对36例患有面部轻度痤疮的受试者,采用自身左右面部对比的方法,采用胶原贴敷料治疗。在治疗前、治疗1周和治疗4周对面部皮肤角质层含水量、经皮水分丢失、皮脂量、皮肤颜色进行测试;采用炎症性皮损和粉刺计数判定痤疮皮损改善情况。结果患者治疗侧面部皮肤角质层含水量显著升高（P〈0．05）;经皮水分丢失明显下降（P〈0．01）,治疗侧发生皮肤红斑,粗糙和脱屑低于对照侧面部皮肤。治疗侧炎性丘疹数目减少,红斑指数下降,但与对照侧相比无统计学差异。所有受试者均未出现不良反应。结论胶原贴敷料单独使用可促进轻度痤疮患者的面部屏障功能的修复,同时对于炎症性皮损、皮肤红斑反应有一定的抑制作用。     

Acne vulgaris: an investigation into the number of anaerobic diphtheroids and members of Micrococcaceae the in normal and acne skin

A quantitative study was made of the microflora of 174 acne and 68 non-acne subjects. Two groups of organisms were investigated, the anaerobic diphtheroids and members of the Micrococcaceae. The results showed high numbers of both groups of bacteria in skin bearing blackheads, papules or pustules and in non-acne adolescent skin. There were significantly lower numbers of bacteria in the pilosebaceous ducts of normal looking skin in acne areas and in pre-adolescent skin when compared with non-acne adolescent skin. It is suggested that increased numbers of bacteria alone do not predispose to acne, but that their interaction with the skin, which is a function of the localized skin environment, may be important.