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Skin colonization by Malassezia species in neonates: a prospective study and relationship with neonatal cephalic pustulosis.

OBJECTIVES: To assess skin colonization by Malassezia species in full-term healthy newborns, to investigate factors associated with colonization, and to look at acnelike cephalic pustulosis associated with this carriage. DESIGN: Samples were obtained from neonates and their mothers 0 to 5 days after birth and again 3 weeks later. Clinical patterns of common acnelike pustulosis were reported as mild (<10 papulopustules), moderate (> or =10 papulopustules), or absent. Direct examination and culture of sample. Identification of yeasts was based on microscopic and physiologic criteria. SETTING: A maternity hospital and the pediatric dermatology unit of a university hospital. PARTICIPANTS: Consecutive series of 102 neonates and their mothers. MAIN OUTCOME MEASURES: Incidence of skin colonization and type of Malassezia species found in neonates and correlation with neonatal cephalic pustulosis (neonatal acne). RESULTS: At the first visit, 11 neonates and 36 mothers had cultures positive for Malassezia. Malassezia sympodialis and Malassezia globosa were preferentially cultured. At 3 weeks, 29 (52%) of 56 neonates and 18 (32%) of 56 mothers had cultures positive for only M sympodialis and M globosa. Breastfeeding was not associated with a higher prevalence of Malassezia carriage in neonates. Malassezia colonization was higher when pustulosis was more severe and M sympodialis was found in pustules. CONCLUSIONS: Malassezia colonization begins at birth and increases in the first weeks of life. A high prevalence of M sympodialis in neonates is noted from birth. Its association with neonatal acne is confirmed. Further investigation is needed to study the role of sebum secretion rate and quality in the neonatal period.

Acne Vulgaris↗

Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis.

BACKGROUND: Progressive macular hypomelanosis is a common hypopigmentation mainly on the central parts of the trunk, predominantly in young adults, especially women. It is often mistaken for pityriasis versicolor and pityriasis alba. It occurs in all races and has been described in many parts of the world. We discovered follicular red fluorescence restricted to lesional skin. We suspected a relation with a porphyrin-producing bacteria residing in sebum of the pilosebaceous duct, and we therefore performed a study in 8 patients. Observation In all biopsy specimens taken from lesional skin of 8 women, we could demonstrate gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular lymphocytic infiltrate was seen. In all but 1 patient, Propionibacterium acnes was yielded from cultured biopsy specimens taken from follicular lesional skin. Healthy follicular skin did not show bacteria in histological sections, and cultures did not yield anaerobic bacteria. CONCLUSIONS: There seems to be a relation between the presence of P acnes and the hypopigmented macules. We propose that a factor is produced by these strains of P acnes, which interfere with melanogenesis. Based on these observations, we are undertaking a clinical trial to find a treatment for this troubling, intractable disease.

Adolescent↗

The histopathology of closed and open comedones of Favre-Racouchot disease.

OBJECTIVE: To determine the distinction between a comedo and an infundibular cyst of Favre-Racouchot disease. SETTING: A university hospital. PATIENTS: From the 8 patients included in the study, 19 cysts and comedones were evaluated. MAIN OUTCOME MEASURE: The distinguishing features between the cysts and comedones of Favre-Racouchot disease. RESULTS: All lesions were histologically indistinguishable from the primary comedones of acne vulgaris, except for the presence of a marked actinic elastosis in the surrounding dermis. The presence of a variable number of hair shafts and an abundant amount of bacteria, which was positive in the results of Gram staining and periodic acid-Schiff reaction and intermingled with sebum and eosinophilic laminated horny material within the dilated infundibulum, characterizes a comedo and differentiates it from an infundibular cyst. CONCLUSIONS: The cysts and comedones of Favre-Racouchot disease are closed and open comedones. They can be easily differentiated from an infundibular cyst by the histopathologic features rather than by the connection to the surface.

Aged↗

In search of the elusive benign cystic ovarian teratoma: application of the ultrasound "tip of the iceberg" sign.

The benign cystic ovarian teratoma (dermoid) has distinctive ultrasonic features that differentiate it from other adnexal masses. The most frequent sign is the presence of highly reflective irregular solid components within a fluid-containing adnexal mass. In vitro scans of surgical specimens have shown that the strongly reflective echo pattern is caused by the hair and sebum within the dermoid. Calcium is often sparse or absent. Acoustic shadowing from the hair may totally obscure the back wall of a large, clinically evident mass; hence the term "tip of the iceberg" sign. Recognition of this sign reduces the possibility of a false negative interpretation and confusion with a "bowel gas pattern."

Dermoid Cyst↗

Tea tree oil concentration in follicular casts after topical delivery: determination by high-performance thin layer chromatography using a perfused bovine udder model.

Tea tree oil, a popular antimicrobial agent is recommended for the treatment of acne vulgaris, a disease of the pilosebaceous unit. Tea tree oil formulations (colloidal bed, microemulsion, multiple emulsion, and liposomal dispersion containing 5% w/w tea tree oil) were applied to bovine udder skin. The follicular uptake of tea tree oil upon application was determined by a cyanoacrylate method. Tea tree oil was determined by quantifying terpinen-4-ol content using high-performance thin layer chromatography. The accumulation of tea tree oil in the follicular casts was 0.43 +/- 0.01, 0.41 +/- 0.009, 0.21 +/- 0.006, and 0.16 +/- 0.005 percentage by weight (milligram oil/gram of sebum plug) for microemulsion, liposomal dispersion, multiple emulsion, and colloidal bed, respectively. This is the first study of its kind to quantify tea tree oil concentration in the follicles.

Adhesives↗

Centrioles, microtubules and microfilaments in activated mononuclear and multinucleate macrophages from rat peritoneum: electron-microscopic and immunofluorescence microscopic studies.

In male Wistar rats of the BD I strain, mononuclear macrophages and multinucleate giant cells obtained from the peritoneum 1 day to 5 weeks after implantation of coverslips coated with dermoid cyst sebum, were examined by light microscopy and immunofluorescence microscopy, using antibodies specific for actin and tubulin and also by scanning and transmission electron microscopy. In activated mononuclear macrophages, microtubules radiate from the centrioles, situated in the perinuclear area, into the cytoplasm and the major cell processes. Microfilaments form a dense meshwork beneath the plasmalemma. When mononuclear macrophages fuse to form multinucleate giant cells, the initially unordered ("Foreign body") syncytia still reveal the original distribution patterns of centrioles, microtubules and microfilaments similar to those seen in the individual cells. In the ordered (Langhans) multinucleate giant cell all centrioles are accumulated in a main pluricorpuscular central group. Centrioles are the initiating and organising centres in the formation of microtubules. From the centrioles microtubules extend into the entire cytoplasm of the syncytium as a uniformly organised, stellate, radial system. The centrosphere, which is characteristic for ordered multinucleate giant cells, seems free from microfilaments, which form a ring-shaped woven network encircling the nuclei. Depolymerisation and inhibition of microtubules upon exposure to colchicine, indicates that both the organisation of the cytoplasm and the cellular movements depend on the undisturbed coordination of centrioles, microtubules and microfilaments. This applies also to the fusion of mononuclear macrophages to form syncytia, the ordering processes within multinucleate giant cells, and the function of ordered giant cells.

Animals↗

Ligand-dependent activation of the melanocortin 5 receptor: cAMP production and ryanodine receptor-dependent elevations of [Ca(2+)](I).

The melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands. The purpose of this study was to identify the peptide that functions as a natural ligand at the MC5R in the skin. alpha-MSH, ACTH1-39, ACTH1-17, ACTH1-10, and ACTH4-10 all increased the production of cAMP in HEK293 cells transfected with the mouse MC5R. alpha-MSH and ACTH1-17 were the most potent in this respect. In addition, all peptides stimulated a rapid and transient increase in [Ca(2+)](i), and, ACTH1-10 was the most potent. The increases in [Ca(2+)](i) were of intracellular origin, but not associated with inositol phosphate production. The elevations in [Ca(2+)](i) were reduced by ruthenium red and procaine and it is therefore possible that they were mediated via ryanodine receptors.

Adrenocorticotropic Hormone↗

Distribution, teratogenicity, and embryonic delivered dose of retinoid Ro 23-9223.

Ro 23-9223 is a highly lipophilic aromatic retinoid with antiproliferative and sebum supressive effects in preclinical disease models of acne. To investigate the relation between Ro 23-9223 developmental toxicity, drug distribution, and transplacental transfer, groups of pregnant hamsters were given oral doses of 50-500 mg/kg Ro 23-9223 on days 8 and 9 of gestation. The teratogenic phenotype induced at doses greater than 125 mg/kg per day was similar to that found after exposure to doses of 13-cis-retinoic acid (isotretinoin, Accutane) greater than 37.5 mg/kg per day. Oral bioavailability of Ro 23-9223 was very low compared to 13-cis-retinoic acid. The highest concentrations of Ro 23-9223 were found in maternal liver, lung, adipose tissue, cardiac muscle, and placenta, whereas only little of the compound crossed the blood-brain barrier. Based on embryo AUC, Ro 23-9223 had a 30- to 50-fold greater embryo:maternal concentration ratio than 13-cis-retinoic acid plus its bioactive metabolites following similar doses of the two retinoids. In preclinical pharmacology studies, oral doses of Ro 23-9223 (5 mg/kg per day) and 13-cis-retinoic acid (10 mg/kg per day) produced comparable gland size reductions in the hamster ear sebaceous gland reduction assay. Under these conditions, Ro 23-9223 plasma AUC was 40 times smaller than that of 13-cis-retinoic acid plus its bioactive metabolites. Assuming that the near linear dose-exposure relationship of Ro 23-9223 extends beyond the dose range of this study, embryo AUCs of Ro 23-9223 and 13-cis-retinoic acid (plus metabolites) would be near identical following pharmacologically equivalent doses. A comparison of embryo retinoid AUCs suggests a 4-fold lower teratogenic potency of Ro 23-9223 compared to with 13-cis-retinoic acid. Despite high embryo levels in hamsters, the data suggest an improved therapeutic index for Ro 23-9223 compared with 13-cis-retinoic acid in a preclinical acne disease model.

Abnormalities, Drug-Induced↗

Application of computer taxonomic techniques to the study of cutaneous propionibacteria and skin-surface lipid.

Colonisation of the forehead by propionibacteria and the composition of both free fatty acid and fatty acid of the triglyceride fraction of skin-surface lipid were studied, and the results were analysed using numerical taxonomic techniques. The density and prevalence of propionibacteria increased with age in a population of 230 children aged 5-18 years. The fatty-acid composition of casual sebum on the forehead changed with age, suggesting that the prevalence and density of organisms may be related to lipid composition. Cluster-analysis techniques revealed groups of individuals who resembled each other with respect to their triglyceride and free-fatty-acid profiles. These groups tended to consist of subjects who were of a similar age and maturity, and who were similarly colonised with propionibacteria. However, no relationship was evident between the composition of lipid and clinical acne.

Adolescent↗

Tissue connections in a transplantable virus-producing sebaceous adenoma of the mouse.

In this study a transplantable sebaceous adenoma is presented, which maintained its histological structure with similarities to normal sebaceous glands over a long series of transplantations. From the periphery toward the center a basal lamina, an outer layer of undifferenciated stem cells, loosely connected secreting tissue, a tightly packed zone of close cell attachment, and finally a central sebaceous zone can be distinguished. Special reference is made to the belt-like region around the zone of cell lysis and sebum accumulation, which forms a barrier to the surrounding tissue by means of numerous cell adhesions in the form of desmosomes. Relatively few virus particles of the retrovirus group, particularly type A particles, were found in any of the examined tumors.

Adenoma↗

[Pityriasis versicolor due to Malassezia ovalis].

In a randomly collected series of 175 cases of pityriasis versicolor in residents of the central-northern part of Venezuela, 13% of the patients were infected with ovoid unicellular units of the causal fungus (Malassezia ovalis) and 87% with globous unicellular units in the scales (M. furfur). Only globous unicellular units (Pityrosporum orbiculare) were seen outside the active lesions and in these, after the successful treatment with ketoconazole. The median age of 40 'ovalis' patients was 37.5 years; the same in 40 'furfur' patients was 24.5 years. The median age at the moment of discovering the first lesions among 'ovalis' patients was 31; among 'furfur' patients this was 20 years. There were 16 male patients among the 'ovalis' and 24 among the 'furfur' groups of 40. The topographic distribution of the lesions varied according to the type of the invader. M. ovalis prevailed on the trunk below the waist-line and on the limbs, mainly on buttocks and upper legs. M. furfur prevailed on the chest, neck, face and upper limbs. The hypothesis is offered that the ovoid agent of pityriasis versicolor preferentially occupies the less sweating and sebum-producing parts of the body in older (and drier) persons than the globous type does.

Adolescent↗

Effects of cyproterone acetate and carboxylic acid derivatives on the sebaceous glands of the Syrian hamster.

The Syrian hamster ear model was used to study effects of the anti-androgen cyproterone acetate and of the anti-lipogenic compound 17beta-carboxylic acid methyl ester and its ethyl ester. The steroid derivatives were applied topically in a 1-2% concentration or given systemically. Response of sebaceous gland was measured by means of cell proliferation (3H-TdR autoradiography) and by gland size (histoplanimetry). Cyproterone acetate significantly reduced the labelling and the planimetric value, both topically and systemically. The carboxylic acid derivatives, which block the 5alpha-reductase were ineffective. The new animal model is a sensitive and suitable means to study inhibition of sebum production.

Androgen Antagonists↗

Oxidative enzymes in the sebaceous glands of the domestic cat.

The distribution and activities of several oxidative enzymes in various regions of the sebaceous glands of the domestic cat have been studied. The results obtained emphasize the outstanding importance of NADP-linked dehydrogenases for lipogenesis during sebum production. In particular, the reactions for glucose-6-phosphate dehydrogenase were very strong. Among the NAD-linked dehydrogenases investigated, lactate dehydrogenase showed strong activity in the peripheral cells of the sebaceous gland. The reactions for cytochrome oxidase and succinate dehydrogenase were weaker.

Animals↗

[Modern antimycotics. What the treating physician needs to know].

The treatment of dermatophytoses is a complex process influenced by the properties of the antimycotic and the causative agent as well as by patient-related factors. Both the minimal inhibition concentration and the drug concentration in the infected tissue influence treatment success. Dermatophytes can be present as arthrospores in the skin, nails or hair. Non-proliferating dermatophytes (arthrospores) are less susceptible to antimycotics than proliferating ones, particularly to antibiotics which act through the inhibition of fungal ergosterol synthesis. Non-proliferating dermatophytes do not synthesize ergosterol, a essential component of fugal cell membranes. Also, dermatophytes accumulating in hollow spaces mostly in the nail plate, cannot be reached by antimycotics. The concentration of terbinafine and itraconazole is very high in sebum. This is of importance in the treatment of dermatophytoses localized to in the stratum corneum and in or around the hair. Preadolescent children do not have functioning sebaceous glands; this explains the difficulties in the treatment of pediatric tinea capitis.

Antifungal Agents↗

[The extraneuronal cholinergic system of the skin. Basic facts and clinical relevance].

Acetylcholine (ACh) is a prototypical neurotransmitter that has recently been recognized to occur extraneuronally in a large variety of cells. ACh and its nicotinic and muscarinic receptors are produced in the epidermis and in the adnexal structures of the skin in a highly complicated pattern. They are also produced in melanocytes, fibroblasts, endothelial cells and immune cells. Through autocrine, paracrine and endocrine mechanisms, the cholinergic system is involved in the basic functions of the skin, such as keratinocyte differentiation, epidermal barrier formation, sweating, sebum production, blood circulation, angiogenesis and a variety of immune reactions. Hence diseases like acne vulgaris, vitiligo, psoriasis, pemphigus vulgaris and atopic dermatitis may be influenced. The exploration of the extraneuronal cholinergic system of the skin has only just begun.

Acetylcholine↗

[Christ-Siemens-Touraine syndrome].

The Christ-Siemens-Touraine syndrome (CST syndrome) is the rare an- or hypohidrotic form of the ectodermal dysplasia. During embryonic development, the formation and maturation of the central nervous system and the epithelia of the sense organs, skin, teeth, hair (and less frequently the nails) are disturbed. In addition to the cosmetic impairment, insufficient or absent secretion of sweat and sebum is particularly discomforting as it leads to extreme heat intolerance. The decreased number of apocrine sweat glands and mucous glands in the upper nasopharynx results in diminished resistance to respiratory infections. We describe typical features of the disease in a 60 year old female patient, distinguishing this disease from other forms of ectodermal dysplasia. Diagnostic criteria as well as therapeutic options are discussed.

Diagnosis, Differential↗

Functional analysis of the stratum corneum of scalp skin: studies in patients with alopecia areata and androgenetic alopecia.

Because of the presence of thick long hairs on the scalp, little information is available concerning the functional characteristics of the stratum corneum (SC) of scalp skin. We therefore conducted a functional study of the SC of lesional scalp skin of patients with alopecia areata and of patients with androgenetic alopecia. We compared the scalp with the cheek and the flexor surface of the forearm (volar forearm). The water barrier function of the scalp SC of both patient groups, in terms of transepidermal water loss (TEWL), was almost comparable to that of the volar forearm, and was far better than that of facial skin. However, hydration of the scalp skin surface, as evaluated by measurement of high-frequency conductance, was markedly higher than that of facial skin, and showed significantly higher values than the volar forearm. These characteristics seem to be dependent, at least to some extent, on the amount of sebum-derived skin surface lipids because these were abundant on the scalp skin. Moreover, removal of skin surface lipids led to a significant decrease in skin surface hydration. The superficial corneocytes, the size of which reflects the proliferative activity of the epidermis, were substantially smaller on the scalp than on the volar forearm but significantly larger than on the cheek. These findings suggest that the rate of turnover of the scalp epidermis is intermediate between that of the facial and volar forearm epidermis. We conclude that the SC of the scalp skin in humans is functionally distinct from that of the face and extremities.

Adolescent↗

Perspiration versus saliva--basic aspects concerning their use in roadside drug testing.

Various aspects concerning the practical application and forensic interpretation of data obtained by saliva drug testing and drug monitoring from the skin surface are discussed. Basic information on the composition of saliva and skin secretions and their particular transport mechanisms, as far as known, are given. For drugs of abuse secretion into saliva is suggested to be by passive diffusion and to depend on lipid solubility, pKa, plasma protein binding and on the pH of saliva. Drug molecules from blood are considered to reach the skin surface by various routes such as by sweat and sebum as well as by inter- and/or transcellular diffusion. The role of the stratum corneum as a temporary drug reservoir exceeding positive drug findings in urine is outlined. Current data on opioids, cocaine metabolites, cannabinoids and amphetamines detected in saliva and on the skin surface are reviewed. Aspects of collection, processing and analysis of the samples for implementation in roadside testing are addressed. The requirement of test sensitivity covering the broad concentration ranges and the importance of test specificity bearing in mind that the parent drug is the main analyte present in those specimens is stressed. Theoretical and practical findings on frequently abused drugs are discussed with regard to the possibilities and limitations of drug monitoring from saliva and perspiration to support a suspicion of actual or recent drug administration.

Drug Monitoring↗