Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema

Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.     

Non-invasive measurement of the vascular dynamics of dermographism--comparative study in atopic and non-atopic subjects

There is no dissent about the vascular origin of dermographism (D); however, the microcirculatory events underlying this phenomenon are not yet elucidated sufficiently. In particular, the vascular mechanisms producing the white D pattern in atopics are a matter of divergent hypotheses. In order to quantify the D phenomenon reproducibly, we constructed an easily usable device called "Dermographometer" which enables us to apply constant stretching pressure to the skin. We were able to investigate several parameters of microvascular cutaneous reaction to defined skin stretching pressure by laser-Doppler-microfluxmetry and infrared-thermography. These measurements were performed on 23 patients with atopic eczema (AE) and 21 healthy controls under standardized investigative conditions. Only patients under similar therapeutic regimens (no corticosteroids) with dry or lichenified skin inflammation (lumbar area) were included in the study. The basic values of laser-Doppler-fluxmetry (LDF) showed a significant reduction in the intensity of hyperemia in the patients from those in the normal controls; this reaction depended on the visual degree of the dermographic blanching effect (white, delayed white, indifferent, pale-red). Patients with white or indifferent D had the lowest rises in blood flux; those with delayed white or pale-red D had more elevated blood fluxes, but these were still clearly below the mean levels of normal red D. Infrared-thermography showed a significant diminution of both the rise and plateau phase of the radiating temperature in comparison to the controls. Our results support the hypothesis that white D (including different subtypes of its pallor) depends on the degree of local vasoconstriction, possibly in combination with altered blood flow in cutaneous shunt vessels.     

Pooling the evidence: A review of swimming and atopic dermatitis

Swimming is an excellent form of aerobic exercise and is an essential life skill. Many children with atopic dermatitis (AD) are advised not to swim because of concerns about negative impacts on their skin disease, and some children with AD do not swim because they are self-conscious about the appearance of their skin. We aimed to perform a narrative review of the available literature on swimming and AD and scientifically analyze the potential impact of all components of swimming in AD—water, skin barrier, swimming gear, and exercise. Studies examined the impact of swimming on the skin barrier and the relative contraindications to swimming. Constituents of water which may affect AD include hardness, pH, temperature, antiseptics, and other chemicals. Potential interventions to reduce damage included emollient application, special swim gear, and showering post-submersion. The benefits of swimming as a form of exercise in AD included reduced sweating, cardiorespiratory fitness, and maintenance of healthy weight. Drawbacks of swimming as a form of exercise in AD included the limited benefit on bone mineral density. Future research should examine the impact of swimming on flares of AD using noninvasive biomarkers as well as clinical severity assessment and assess the role for different types of emollient as an intervention for optimal eczema control. This review highlights gaps in the scientific literature on swimming and AD and provides evidence-based guidance on interventions to minimize deleterious effects on skincare and maximize opportunities for children with AD to swim.     

The role of cutaneous dendritic cells in the immunopathogenesis of atopic dermatitis

We review the immunology of atopic dermatitis (AD) and focus attention on the role of cutaneous dendritic cells. AD is a complex immune-mediated skin disorder characterized by the recruitment of both CD4+ and CD8+ T cells into the skin. T-helper (Th) 2-type cytokines are dominant in acute AD skin, while both Th1- and Th2-type cytokines are present in chronic AD. Cutaneous dendritic cells, which are present in increased numbers within AD skin, are believed to play a key part in the activation of T cells in the skin. They may also help to determine the pattern of cytokines produced by activated effector T cells.     

Identification of subjects with atopic dermatitis in questionnaire studies

Patients with contact allergy to sesquiterpene lactones (SLs) are usually hypersensitive to Asteraceae plant products such as herbal teas. The objective of this study was to show sensitizers in chamomile tea by patch testing with thin-layer chromatograms. Tea made from German chamomile was separated by thin-layer chromatography. Strips of the thin-layer chromatograms were used for patch testing SL-positive patients. 15 (43%) of 35 patients tested positively to 1 or more spots on the thin-layer chromatogram, with many individual reaction patterns. Patch testing with thin-layer chromatograms of German chamomile tea showed the presence of several allergens.     

Recent progress in studies of infantile hemangioma

A hallmark of infantile hemangioma, the most common tumor of infancy, is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The growth and involution of infantile hemangioma is quite different from other vascular anomalies, which do not regress and can occur at any time during life. Some hemangioma lesions can be extremely disfiguring and destructive to normal tissue and may even be life‐threatening. Unfortunately, existing therapeutic approaches have limited success and significant adverse effects of some treatment modalities limit their use. Better understanding of the pathogenesis of hemangioma will enable the development of better therapeutic strategies. Here, we review recent studies and new hypotheses on the pathogenesis of the tumor. Detailed mechanisms of activated vascular endothelial growth factor signaling in tumor cells, identification of their origin and characterization of multipotent stem cells that can give rise to infantile hemangioma are shedding new light on this intriguing vascular tumor.     

Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic subjects.

Clinical dryness of the leg skin is a common problem among dermatological patients. The efficacy and safety of 12% ammonium lactate emulsion (Keratisdin) for the treatment of dry skin on the legs of atopic and non-atopic subjects has been assessed by clinical criteria and by five different non-invasive methods. These methods measure biophysical parameters such as electrical capacitance of stratum corneum, skin surface lipids, transepidermal water loss (TEWL), skin surface topography (scanning electron microscopy and image analysis) as well as the biomechanical properties of the skin. Treatment with the test emulsion significantly reduced the severity scores for dryness, desquamation and pruritus when measured 15 days later. All patients tested showed a significant increase in electrical capacitance, skin surface lipids, extensibility and firmness of the skin, and an improvement in the skin barrier function and skin surface topography. This study showed that non-invasive techniques are excellent complementary tools in clinical studies.     

Dermatomyositis: comparative studies of cutaneous photosensitivity in lupus erythematosus and normal subjects

PURPOSE: Cutaneous features of dermatomyositis (DM) strongly suggest that ultraviolet (UV) radiation plays an important role in the pathogenesis of the disease. However, the incidence and the nature of photosensitivity in this disorder have not been established. The aim of this study was to investigate the UVB (290-320 nm) minimal erythema dose (MED) in DM patients in comparison with those in lupus erythematosus (LE) and healthy controls. METHODS: Non-irradiated back skin of 75 Caucasians with skin types II and III according to the Fitzpatrick classification were present in three different subject groups and tested for photomanifestation on non-irradiated suprascapular back skin with an ETG-1 Erythemtester. The first group included 19 DM patients, the second 30 patients with LE, and the third 26 healthy control volunteers. The MEDs were determined 24 h after irradiation adjusted according to skin type. RESULTS: Nine of the 19 DM patients (47.4%) demonstrated reduced MEDs to UVB radiation. Seven DM patients (36.8%) had a history of increased cutaneous photosensitivity and four of these (21.1%) reported diseased aggravation after sun exposure. Both the DM and LE patient groups showed reduced MED to UVB radiation (P<0.05) compared with the control group (19.2%). Increased erythemal sensitivity to UVB irradiation was found more frequently in patients with systemic LE and cutaneous discoid LE, than in those with subacute cutaneous LE. CONCLUSION: DM patients, similar to those with LE, showed a significantly reduced MED to UVB irradiation compared with healthy persons.     

Late adverse effects after soft X-ray therapy of cutaneous malignancies: pruritus, burning, epiphora and insufficient occlusion of the mouth

Background Pruritus, burning, epiphora and insufficient occlusion of the mouth have been less extensively studied than cosmetic changes in irradiated fields. Objectives How frequent are these late adverse effects? Do they usually occur permanently? Are they influenced by treatment and tumour parameters, sex and age of the patients? Methods Patients were interviewed at least once later than 90 days after soft X‐ray therapy. Results Pruritus has been reported in 18.5% of the interviews, burning in 7.7%, epiphora in 36.2% and insufficient occlusion of the mouth in 11.5%. Patients were usually not permanently troubled and irritated by these symptoms: pruritus more than once per week was reported in every interview for 0.6% of the fields, burning for 0.2%, epiphora for 6.4% and insufficient occlusion for 0%. Irritation by these symptoms has been stated in every interview for 5.1% of fields around the eye and for 1.4% of fields at other sites. Late pruritus, burning and epiphora were less frequently reported after irradiation with lower total doses, lower time–dose–fractionation factor (TDF) and by men. Patients older than 70 years of age experienced pruritus and burning less frequently. The largest diameter of the irradiated field influenced pruritus and the half value depth of the X‐rays influenced burning and epiphora. Conclusions Late pruritus, burning, epiphora and insufficient occlusion of the mouth do not considerably reduce the value of soft X‐ray therapy because these adverse effects usually are not experienced permanently. Total dose and TDF should not be chosen higher than necessary.     

Infrared-spectroscopic determination of the water content of the horny layer in healthy subjects and in patients suffering from atopic dermatitis

Summary Infrared spectroscopic measurements of hydration of the stratum corneum before and after stripping the skin five and ten times with scotch tape are reported. Investigations on 64 healthy persons show that for individuals over 45 and under 15 years of age the range of the measurement values is strikingly larger than for persons in the age group 15–45 years of age. A small, but not significant reduction in the measurement values is found in females as compared to males. A comparison of the clinically unaffected skin of atopic dermatitis patients with the skin of normal persons points to an increase in the hydration of the stratum corneum of atopic dermatitis patients, which is especially evident in patients who show clinical evidence of dry and rough skin.Supported by the Deutsche Forschungsgemeinschaft (grant Gl 91/4)     

Cutaneous reactions and sensations after intracutaneous injection of vasoactive intestinal polypeptide and acetylcholine in atopic eczema patients and healthy controls

Received: 24 July 1997     

非特应性的湿疹皮炎患者皮肤菌群的测定与分析

目的：探讨非特应性的湿疹皮炎患者携带细菌尤其是金黄色葡萄球菌（金葡菌）的携带情况。方法：选取正常人30名及门诊非特应性的湿疹皮炎患者186例，以棉签法分别在正常人及皮损部位反复擦拭后进行细菌培养及鉴定。结果：正常人未检出金葡菌；湿疹继发感染患者皮损金葡菌及细菌总检出率均为92.9%；非特应性的湿疹皮炎患者金葡菌检出率和细菌总检出率分别为30.1%和67.7%；临床无感染的湿疹皮炎患者金葡菌检出率和细菌总检出率分别为25.0%和65.7%，后两者金葡菌及细菌总检出率均显著低于湿疹继发感染患者，而金葡菌检出率显著高于正常人。结论：金葡菌与一部分非特应性的湿疹皮炎可能有一定的关系。     

Study of three complementary techniques for measuring cutaneous hydration in vivo in human subjects: NMR spectroscopy, transient thermal transfer and corneometry – application to xerotic skin and cosmetics

Background/aims: The aim of this study was to determine the capability and the analytical quality of three different in vivo, non‐invasive, quantitative methods for measuring skin hydration: two innovative methods that have been used for more than eight years – nuclear magnetic resonance spectroscopy (NMR‐S) and transient thermal transfer (TTT) – and the more widely used and conventional corneometry. Methods: The work presented evaluated the capability and precision, as well as cutaneous exploration depths, of the three methods. Experiments were carried out in vivo following the hydration, in kinetic terms, induced by topic application of reference moisturizing products. Spatio‐temporal efficacy of a lipolotion was also studied by the TTT method. Cases of xerotic skin were studied with TTT and corneometry. Results: The results obtained showed better repeatability and reproducibility with the TTT and NMR‐S methods than with corneometry. NMR‐S is one of the only direct hydration measurement methods. It measures skin hydration down to the outer dermis with high precision. It is indicated for products having an action down to the deep cutaneous layers. By changing thermal power parameters, the TTT method can determine hydration to the outer, middle or deep epidermal layers. It is, therefore, possible to track the penetration of products in various layers of the epidermis. The small size of the probe enables the hydration measurement of skin sites (lips, eyelids) that were not, up to now, measurable with the two other methods. Corneometric investigations are restricted to the surface of the horny layer; measurements are easy and rapid but influenced by the composition of products applied to the skin and their phases: aqueous, oily or ionic. The xerotic skin study highlights the importance of exploration in different layers of the epidermis, as dehydration concerns not only the upper layers of the epidermis but also the medial and deep layers. With the TTT method, it has been possible to highlight the penetration dynamics of a lipolotion with, initially, an increase in the hydration in the outer epidermis, followed 3 h later by a transfer from the outer to the middle epidermis. Conclusion: NMR‐S, TTT and corneometry represent three possible ways to assess skin hydration. Because they explore different cutaneous depths, they are more complementary than competitive. Transient thermal transfer, although a semi‐direct method, is a precise, informative, and innovative solution to evaluate skin hydration at different epidermal depths and sites.     

Laser induced autofluorescence studies of animal skin used in modeling of human cutaneous tissue spectroscopic measurements

BACKGROUND/PURPOSE: Laser-induced autofluorescence spectroscopy provides excellent possibilities for medical diagnostics of different tissue pathologies including cancer. However, to create the whole picture of pathological changes, investigators collect spectral information from patients in vivo or they study different tumor models to obtain objective information for fluorescent properties of every kind of healthy and diseased tissue. Therefore, it is very important to find the most appropriate, and close to the human skin, animal samples from the fluorescence point of view, which will allow the extrapolation of the animal data to human spectroscopic diagnostics. METHODS: In the present work, we examined the autofluorescence properties of different animal skin tissues, which are considered as the most common skin models. A nitrogen laser was used as an excitation source. Samples of healthy mouse, chicken and pig skin in vivo and/or ex vivo were studied and were compared with results obtained from investigations of healthy human skin in vivo. RESULTS AND CONCLUSION: Specific features of the recorded spectra are discussed and the possible origin of the obtained fluorescence signals is proposed. Quantitative evaluation of data extrapolation for each skin type is also depicted.     

A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0-42 months

BACKGROUND: There is strong evidence that the incidence and prevalence of atopic diseases is increasing. However, estimates of the prevalence of atopic dermatitis (AD) have varied greatly in the U.K. and most parts of the developed world. OBJECTIVES: The aim of the study was to estimate the prevalence and incidence of AD between the ages of 0 and 42 months in children born in the 1990s in a defined population in the U.K. DESIGN: We used data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a large population-based study in the U.K. that enrolled all pregnant mothers who were resident in Avon and had their delivery date falling between 1 April 1991 and 31 December 1992. Since then ALSPAC has collected a wide range of data from the newborns and their parents. Data reported here were collected at 6, 18, 30 and 42 months using parental reports in a postal questionnaire. Of the 14 009 children originally enrolled 8530 provided information on AD in each of the four follow-up questionnaires. We defined AD as a report of rash in at least two of the four questionnaires. Incidence risk was defined as the percentage of new cases of AD between follow-up questionnaires, out of the total number of children whose parents had not reported that they had AD by the time of the previous follow-up. RESULTS: Period prevalence of 21.0%, 25.6%, 23.2% and 19.9% were observed at ages 0-6, 6-18, 18-30 and 30-42 months, respectively. The corresponding incidence risks were 21.0%, 11.2% and 3.8%, at 0-6, 6-18 and 18-30 months, respectively. There were no gender differences in either the incidence or prevalence of the disease. CONCLUSIONS: Results from this large, prospective study are consistent with recent reports of increased incidence and prevalence of AD. Health planners can use our estimates of incidence and prevalence to project the number of children likely to suffer from AD during infancy and early childhood, and thus to determine the human and financial resources required.     

Biochemical and clinical studies in a case of contact urticaria to potato

Contact urticaria to potato was confirmed by skin testing in a 26–year-old male with atopic dermatitis, birch-pollen rhinoconjunctivitis and a history of immediate finger itching upon handling raw potato. The potato peel was non-reactive. The urticarial reactivity to potato could be transferred by the patient's serum in a Prausnitz-Küstner test, indicating an immunological etiology. Electrophoretic and chromatographic examination of extracts from homogenized potatoes (unexposed to synthetic fertilizers and insecticides) revealed allergenic activity in a heat-labile macromolecular fraction with a mass of 20-30 kdalton migrating towards the anode during agarose gel electrophoresis at pH 8.6 with a mobility similar to that of human α₁-antitrypsin. The technique used for preliminary fractionation of the allergenic activity in a potato extract, similar to crossed immunoelectrophoresis, appears to be a simple and widely applicable technique for the characterization of proteins with this biological activity. A partially purified fraction with allergenic activity, seemingly more stable than the activity in crude homogenates, was obtained by gel filtration and preparative agarose gel electrophoresis. When an antihistamine was also injected, the urticarial reaction to the protein fraction was less pronounced. Pretreatment of the skin with compound 48/80, a histamine releaser, blocked the reaction. Histamine thus seems 10 be the major vasoactive substance mediating the contact urticarial response to potato antigen in this patient.