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.     

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.     

Tenascin-C is upregulated in the skin lesions of patients with atopic dermatitis

BACKGROUND: Tenascin-C is a large, hexameric extracellular matrix glycoprotein that is expressed during embryogenesis, carcinogenesis and wound healing. In normal adult human skin the expression level of tenascin-C is low, but levels are elevated in skin tumors and rise significantly in the dermal compartment during wound healing. Although the expression of tenascin-C could be upregulated by inflammatory cytokines, the role of tenascin-C in atopic dermatitis (AD) is still unclear. OBJECTIVE: To identify genes that plays a role in AD. METHODS: We screened for differentially expressed genes in lesional and non-lesional skin of AD patients using DNA microarray. Then we monitored with quantitative PCR the expression of the novel disease related genes in human keratinocytes or pinnae from NC/Nga mice. RESULTS: We found that tenascin-C gene expression was expressed at higher levels in lesional skin compared to non-lesional skin of the patients, whereas it was not upregulated in the skin of psoriatic patients or healthy controls. In human cultured keratinocytes, tenascin-C was markedly upregulated by IL-4 and IL-13, and moderately upregulated by IFN-gamma. Tenascin-C expression was also upregulated in the AD-like skin lesions induced in NC/Nga mice ears by intradermal injection of mite antigen, and this upregulation was inhibited by prednisolone. CONCLUSION: These results suggest that upregulation of the tenascin-C expression is specific to AD lesions, and that tenascin-C may therefore play a critical role in regulating the underlining inflammatory processes, which are involved in the pathology of AD.     

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.     

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.     

特应性皮炎患者皮肤表面真菌定植分析

目的：观察念珠菌、红酵母、青霉、曲霉在特应性皮炎患者皮肤表面定植情况,分析这4种常见致敏真菌与特应性皮炎症状严重程度的相关性。方法特应性皮炎患者50例,健康对照组20例。刮取特应性皮炎患者皮损部位及非皮损部位的鳞屑（以四肢屈侧为主）、健康对照组肘关节屈侧皮屑行真菌镜检,无1例发现菌丝或假菌丝;将皮屑标本接种于沙氏葡萄糖培养基,置25℃恒温箱内培养,发现真菌及酵母样可疑菌落,转种沙氏葡萄糖培养基斜面,获得纯培养后,根据菌落形态特征及颜色、菌落生长的快慢、镜下孢子及菌丝的特征进行菌种鉴定。结果特应性皮炎组50例,皮损表面检出念珠菌29例（58%）、红酵母17例（34%）;健康对照组20例,检出念珠菌5例（25%）、红酵母2例（10%）,特应性皮炎组念珠菌、红酵母检出率明显高于健康对照组（χ2值分别为6.23、4.10,均P<0.05）。重度患者25例,检出念珠菌19例（76%）、红酵母12例（48%）;中度患者25例,检出念珠菌10例（40%）、红酵母5例（20%）,重度患者皮损表面念珠菌、红酵母检出率明显高于中度患者（χ2值分别为6.65、4.37,均P<0.05）。患者组与对照组青霉、曲霉检出率差异无统计学意义。结论特应性皮炎患者皮肤表面念珠菌、红酵母定植明显高于健康对照组,且重度患者定植率高于中度患者,表明真菌定植的种类与皮肤的健康状况相关,与特应性皮炎患者症状的严重程度相关。     

Neuropeptides concentrations in the skin of a murine (NC/Nga mice) model of atopic dermatitis

BACKGROUND: It has been reported that the expression of neuropeptides (NPs), and the density and structure of peripheral nerves in atopic dermatitis (AD) are different from those in normal skin. OBJECTIVE: We investigated the role of NPs, in the development of AD with quantitative study of substance P (SP) and calcitonin gene-related peptide (CGRP) in the skin of AD-model mice. METHODS: We measured the NPs in the skin of mice (NC/Nga as AD-model mice, BALB/c and C57BL/6 as control) by enzyme-linked immunosorbentassay (ELISA). Peripheral nerve fibers and SP in the skin were stained by immunohistochemical staining, using anti-PGP9.5 antibody and anti-SP antibody. RESULTS: Under conventional condition, SP concentration in AD-like skin lesions of NC/Nga mice was higher than that in non-affected skin of the same mice. Under specific pathogen-free condition, SP concentration in the skin of NC/Nga mice was higher than that in the skin of BALB/c and C57BL/6 mice. In contrast, CGRP concentration in the skin lesions was lower than that in non-affected skin of NC/Nga mice. SP was detected not only in the nerve fibers in the dermis but also in mast cells in the inflammatory areas. CONCLUSIONS: The skin of NC/Nga mice contains more SP congenitally, and environmental factors may aggravate this abnormal condition. We hypothesize that increase of SP accompanied with a decrease of CGRP in the skin may play important roles in the pathogenesis and development of AD.     

Distribution to the skin of epinastine hydrochloride in atopic dermatitis patients

Although the pharmacological profiles and clinical efficacy of antihistamines for patients with atopic dermatitis (AD), one of the representative cutaneous pruritic diseases, have been well documented, the in vivo concentrations of antihistamines in human skin have previously been studied in less detail. In this randomized trial, the suction blister technique was applied to the measurement of the concentrations of epinastine hydrochloride in the extracellular water compartment in comparison with chlorpheniramine maleate in skin from AD patients. A total of 79 patients (mean age, 28.6 years) were randomly allocated to receive either 20 mg of epinastine or 6 mg of chlorpheniramine. Suction blisters were induced on both upper arms in all patients, and blister fluid was obtained for the measurement of concentrations of the 2 test agents by liquid chromatography-tandem mass spectrometry. Epinastine concentrations in 42 samples were 5.02-33.07 ng/mL (mean +/- SD, 14.08 +/- 10.51; median, 7.00), demonstrating that epinastine is distributed to the skin in high concentrations equal to the levels found in plasma and sufficient to exert its variety of pharmacological modes of action. In contrast, chlorpheniramine concentrations in all 37 samples were below the lower limit of quantification (< 0.5 ng/mL). Corresponding to these pharmacological results, a significant decrease of pruritus was observed in AD patients administered epinastine compared with chlorpheniramine. Hence epinastine is likely to be more effective clinically than chlorpheniramine in AD. This is the first report for the determination of in vivo local drug levels of antihistamines in the skin from AD patients.     

Cytokine expression of skin T-lymphocytes from patients with atopic dermatitis.

We analysed the cytokine profile of skin T cells by establishing 11 T-cell lines from adult patients with moderate-to-severe atopic eczema using T-cell growth factors interleukin-2 and interleukin-4. We compared T-cell lines from lesional skin of atopic dermatitis patients with those from non-atopic skin of patients with other skin diseases, observing that T-cell lines of patients with atopic dermatitis unstimulated cultures expressed a Th1 profile. After stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, the cytokine expression showed rapid initial upregulation of Th2 followed by a Th1 profile. Furthermore, strong upregulation of interleukin-10 was observed after 24 h stimulation. Our findings suggest that skin T-lymphocytes from atopic dermatitis patients seem to consist of a heterogenous population of Th1 and Th2 or Th0 cells and the results for secreted cytokines indicate that T-cell lines from each inflammatory skin disease showed the corresponding disease-specific original cytokine profile.     

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.     

Expression of e-selectin in the skin of patients with atopic dermatitis: morphometric study

Adhesion molecules may play an important role in the homing of T-cell subsets into allergen-exposed skin of atopic individuals. The aim of this study was to examine the expression of adhesion molecules in atopic dermatitis skin lesions. Biopsies were obtained from lesions in 30 adult patients with atopic dermatitis and 10 healthy adults as controls. Biopsy specimens were studied by immunohistochemistry for the expression of E-selectin in epidermis and dermis cells. Results showed significant changes in the epithelial cell expression of E-selectin, which were especially pronounced in vascular endothelium of the dermis of atopic dermatitis patients.     

Leukoderma in patients with atopic dermatitis

Atopic dermatitis (AD) is occasionally associated with vitiligo, however, the incidence and conditions of vitiligo or leukoderma, and the characteristics of concurrent AD, remain unclear. We conducted a prospective observational study to investigate the leukoderma‐related clinical manifestations and bioparameters of AD. Because vitiligo in AD lesions is occasionally associated with inflammation, we used leukoderma in this study. Enrolled were all AD patients who had been followed up in our AD outpatient clinic and visited within the previous 4 months. During this period, we carefully inspected whether the patients had leukoderma. Eight of 52 patients had leukoderma (15.4%) and were designated as the leukoderma group, and the remaining 44 patients comprised the non‐leukoderma group. While the ages were statistically not different between the two groups, female preponderance was significantly observed in the leukoderma group. The leukoderma patients tended to have higher values of SCORAD, CCL17/thymus and activation regulated chemokine and lactate dehydrogenase than the non‐leukoderma patients. The leukoderma group was also characterized by a lower frequency of allergic rhinitis and a higher frequency of prurigo lesions. Thus, despite the possession of high AD severity, the leukoderma patients may possibly retain a relatively T‐helper 1‐skewing state in relation to the development of leukoderma and less association with rhinitis.     

Neuronal sensitization for histamine-induced itch in lesional skin of patients with atopic dermatitis

OBJECTIVE: Lowered threshold of neurons (ie, neuronal sensitization) in atopic dermatitis was investigated by testing sensitivity to histamine. DESIGN: Comparative study. SETTING: A dermatological clinic and a research laboratory. PARTICIPANTS: Eighteen patients with atopic dermatitis (AD) and 6 patients with chronic plaque-type psoriasis as well as 14 healthy control subjects. INTERVENTIONS: Histamine prick was performed in lesional and nonlesional skin of patients and in control subjects. MAIN OUTCOME MEASURES: Axon reflex flare and wheal were measured planimetrically, and the itch intensity was rated on a numerical scale (0-10). RESULTS: In nonlesional skin of patients with AD, itch intensity and axon reflex flare were both significantly smaller compared with controls (mean +/- SEM maximum itch, 1.5 +/- 0.3 vs 3.1 +/- 0.2 [P<.05]; mean +/- SEM diameter, 12.3 +/- 2.0 vs 25.3 +/- 2.5 mm [P<.01]). In lesional skin of patients with AD, on the contrary, massive itch was provoked (maximum itch, 4.4 +/- 0.3), although flare was relatively small (diameter, 16.1 +/- 3.4 mm). Itch ratings in patients with psoriasis were low both in lesional and nonlesional skin (maximum itch, 1.3 +/- 0.6 and 1.0 +/- 0.4, respectively). CONCLUSION: As the area of axon reflex flare is an indirect measure of activity in primary afferent neurons, our results suggest a decreased activation of peripheral pruriceptors in patients with AD. The massively increased itch in lesional skin of patients with AD might therefore be based on sensitization for itch in the spinal cord rather than in primary afferent neurons. This sensitization does not appear to be simply based on skin inflammation because histamine-induced itch was not augmented in lesional skin of psoriasis.