Stratum corneum hydration and skin surface pH in patients with atopic dermatitis

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.     

Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis

Background Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces. Objective To study the stratum corneum (SC) covering the areola using noninvasive methods. Methods Eighteen adult healthy subjects comprising nine men and nine women and 18 age‐ and sex‐matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed. Results All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients. Conclusions In adults, the SC barrier function and SC water‐binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD.     

Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis

Atopic dermatitis is an inflammatory skin disease characterized by dryness and itch of the skin. In this study, we measured the phospholipid content and the fatty acid pattern of lesional and lesion-free epidermal keratome biopsies on 15 patients. For comparison, epidermal biopsies were obtained from healthy individuals undergoing plastic surgery. The phospholipid content of atopic epidermis was nearly twice as high as in healthy epidermis. Monounsaturated fatty acids in the phosphoglycerides were significantly increased (p less than 0.001) and n-6 fatty acids were significantly decreased (p less than 0.001) in lesional atopic epidermis compared to lesion-free epidermis. The content of esterified arachidonic acid in phosphatidylcholine from lesional epidermis was only 49% of that found in healthy epidermis (p less than 0.001). The content of free arachidonic acid was 47% higher (p less than 0.05), whereas the content of free long-chain saturated fatty acids was decreased by 29% (p less than 0.01), in lesional compared to lesion-free atopic epidermis. The disease severity, calculated as an arbitrary index, correlated inversely with the n-6 fatty acid content of lesion-free atopic epidermis (r = -0.89, p less than 0.001). Our findings suggest that atopic epidermis is characterized by an increased activity of phospholipase A2 and an incomplete transformation of phospholipids into other lipid classes.     

Neuropeptides in the skin of patients with atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuro-peptides were examined in lesional and non-lesional skin of AD patients (n= 5) and in normal controls (n= 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9·5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0·05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients hut no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetyleholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD.     

Staphylococcus aureus skin colonization in atopic dermatitis patients

A study was conducted to compare the Staphylococcus aureus skin colonization of 21 patients with atopic dermatitis (AD) and 22 healthy controls. It was found that the total aerobe count (total CFU/cm2), the S. aureus fraction thereof and the S. aureus carrier frequency were significantly higher in apparently normal skin of AD patients than in healthy individuals. In addition, compared to normal skin of patients S. aureus density was 100 to 1,000 times higher in the 3 different kinds of lesional skin (dermatitic, lichenified and impetiginized sites). 190 S. aureus strains isolated from the skin of AD patients were tested for sensitivity to 5 topically used antibiotics and the results reported. Besides the biological consequences for the person affected by AD this severe colonization with S. aureus is of epidemiological importance. Several outbreaks of S. aureus infections by dispersal from dermatitic skin have been described. Therefore some preventive and therapeutic aspects are discussed.     

Occurrence of patchy parakeratosis in normal-appearing skin in patients with active atopic dermatitis and in patients with healed atopic dermatitis: a cause of impaired barrier function of the atopic skin

It remains unclear whether an impaired barrier function often seen in areas of normal-appearing skin in patients with active atopic dermatitis (AD) is primary event in nature or secondary to subclinical eczematous change. We then attempted to evaluate the barrier function of normal-appearing skin in both active and healed AD patients, and as well as see whether a subclinical eczematous change exists or not in the normal-appearing skin using a non-invasive method. Transepidermal water loss (TEWL) measurement and exfoliative cytology method for corneal layer were applied in 153 AD patients who have active skin lesions and 29 individuals with completely healed AD for at least 5 years and 40 normal individuals. The TEWL of normal-appearing skin in severe, moderate and mild AD cases was 10.5+/-2.9, 8.3+/-2.4 and 7.3+/-2.1 g/m2 per h, respectively. The TEWL values in severe and moderate cases were significantly higher than the normal controls (6.2+/-1.6 g/m2 per h). However, the TEWL was not deranged in patients with completely healed AD. An exfoliative cytology examination of corneal layer disclosed that patchy parakeratosis appeared in normal-appearing skin in severe, moderate and mild AD cases at a rate of 42, 29 and 19%, respectively. However, no patchy parakeratosis was recognized in patients with completely healed AD. The occurrence of patchy parakeratosis in normal-appearing skin in patients with active AD suggests that an impaired barrier function often seen in normal-appearing skin in AD patients is secondary to subclinical eczematous change in the area.     

IgE-positive epidermal Langerhans cells in allergic contact dermatitis lesions provoked in patients with atopic dermatitis

Summary To see whether or not IgE-bearing epidermal Langerhans cells are specific to skin lesions of atopic dermatitis (AD), we performed immunohistochemical and immunoelectron microscopic examinations of dinitrochlorobenzene (DNCB) contact dermatitis lesions provoked in uninvolved skin of eight patients with AD. In all of the eight examined, IgE-positive epidermal Langerhans cells were observed in the DNCB dermatitis lesions. Typical staining of anti-IgE was absent in the epidermis of normal-appearing skin of five patients with AD. Thus, it is likely that IgE positive epidermal Langerhans cells non-specifically occur in different eczematous diseases provoked in patients with AD.     

Comparative study of staphylococci from the skin of atopic dermatitis patients and from healthy subjects

BACKGROUND: Bacterial infections occur frequently on the skin of atopic dermatitis (AD) patients. The objectives of this study were to evaluate the microbiology of the skin of AD patients for staphylococci, the frequency and density of each species, and their susceptibility to antimicrobial drugs. METHODS: To study the staphylococci present on the skin of 21 AD outpatients and of 12 healthy subjects (HS), cutaneous organisms were obtained using the contact-plate method. RESULTS: Staphylococcus aureus was isolated in 85.7% of AD patients (mild type, 77.8%; moderate type, 87.8%; and severe type, 100%) and in 25% of HS, while Staphylococcus epidermidis was isolated in 83.3% of HS and in 38.1% of AD patients. Among the coagulase-negative staphylococci (CNS) identified, S. epidermidis was the common type and several other CNS were detected in both AD patients and HS. As the eruption grade of dermatitic skin became more severe, the average density of S. aureus increased (severe, 2.68 +/- 0.86; moderate, 2.49 +/- 0.48; mild, 2.28 +/- 0.44). A reversed tendency was seen in S. epidermidis (severe, 1.80; moderate, 1.90; mild, 2.10). Among nine antimicrobial drugs tested against S. aureus, S. epidermidis, and some other types of CNS isolates, vancomycin (VCM) and minocycline (MINO) were the most active, gentamycin (GM) was the less active, and ampicillin (ABPC) was the least active. CONCLUSIONS: The skin of AD patients was more frequently colonized with S. aureus than that of normal controls. As the severity of the AD lesions increased, the numbers of S. aureus isolated increased. The skin of HS was more colonized with S. epidermidis. Other species of CNS were isolated from several cases of AD patients and HS. In addition, S. aureus, S. epidermidis, and the other CNS showed poor susceptibility to some of the tested antimicrobial drugs.     

The epidermal barrier in atopic dermatitis

Epidermal barrier function is abnormal in individuals with atopic dermatitis (AD). It is controversial whether primary epidermal barrier abnormalities alone account for the physiological and clinical abnormalities found in those persons with AD or whether the observed barrier dysfunction is a consequence of primary immunologic abnormalities. Recent evidence is strengthening the argument for the former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has long been an important part of the therapy of AD. Advances in our understanding of the biology of the epidermal barrier and how this relates to the clinical manifestations of this disease has important consequences for new therapeutic approaches in the management of AD.     

Premenstrual deterioration of skin symptoms in female patients with atopic dermatitis

BACKGROUND: Although it has been recognized that women with atopic dermatitis often show menstrual-cycle-associated skin deterioration, information about this subject is meager. OBJECTIVE: To clarify the clinical features of the monthly worsening of atopic dermatitis. METHODS: A total of 286 Japanese women with atopic dermatitis were interviewed to see whether the menstrual cycle had any influence upon their skin lesions, and whether they had symptoms of premenstrual syndrome. Patients suffering from monthly skin deterioration were then observed during and after the monthly worsening. RESULTS: Of the 286 patients interviewed, 134 (47%) had monthly skin deterioration, most of which occurred in the premenstrual week. There was individual difference in severity of the monthly skin worsening. All patients with the premenstrual skin aggravation had symptoms of premenstrual syndrome. CONCLUSIONS: Premenstrual worsening of skin lesions occurs in approximately half of women with atopic dermatitis. The premenstrual skin deterioration is related to the premenstrual syndrome.     

Complement and immunoglobulin deposits in the skin of patients with atopic dermatitis

The immunofluorescent patterns of uninvolved and involved skin biopsies from eight patients with atopic dermatitis were studied, using direct immunofluorescence techniques to identify deposits of the immunoglobulins G, A and M as well as the complement factors C1q, C3, C4, C5, factor B and properdin. Immunoglobulin deposits (mainly IgG) were found in five patients, complement deposits in three patients in the basement membrane zone. In three patients the immunofluorescence was positive for C3, in two patients for C1q, C4 and C5. Regarding the factors of the alternative pathway of the complement system, two patients showed deposits of properdin, one of factor B. The changes were not confined to the eczematous lesions, but were found in uninvolved skin too. The most prominent changes were observed in patients with severe disease.     

Malassezia sympodialis stimulation differently affects gene expression in dendritic cells from atopic dermatitis patients and healthy individuals

It is known that 28-84% of patients with atopic dermatitis exhibit IgE and/or T-cell reactivity to the opportunistic yeast Malassezia sympodialis, which can be taken up by immature monocyte-derived dendritic cells (MDDCs), resulting in MDDC maturation. The aim of this study was to investigate whether MDDCs from patients with atopic dermatitis respond differently to M. sympodialis compared to MDDCs from healthy individuals. Immature MDDCs were stimulated with M. sympodialis and the gene expression profiles were analysed with cDNA arrays containing 406 genes. Our results show that M. sympodialis differently affected MDDCs from patients with atopic dermatitis, and more so in severely ill patients, compared with healthy individuals. Six genes were more than fivefold up-regulated in MDDCs from more than one patient with atopic dermatitis, coding for CD54, CD83, IL-8, monocyte-derived chemokine (MDC), BTG1 and IL-1R antagonist. In healthy individuals this was true only for BTG1. Up-regulations of IL-8 and MDC were confirmed at the protein level. Our findings might reflect an increased trafficking and stimulatory capacity in MDDCs from the patients, which is likely to result in a stronger inflammatory response to M. sympodialis.