Beta adrenergic receptor binding on polymorphonuclear leukocytes in atopic dermatitis.

It has been postulated that the patient with atopic dermatitis has defective beta adrenergic receptor function. However, a more generalized defect is suggested by the observation that cyclic AMP generation is diminished in these patients following stimulation with both isoproterenol and PGE1. To determine the nature of this abnormality, we measured beta adrenergic receptor binding directly on polymorphonuclear leukocyte membranes using the radiolabeled beta adrenergic antagonist (-) [3H]dihydroalprenolol (DHA). DHA binding was studied in 6 mild and 9 moderate-to-severe atopic dermatitis patients, and 8 normal controls using a subsaturating concentration of DHA (0.5 nM) to estimate receptor affinity and a saturating concentration of DHA (30 mM) to determine the total number of receptors per cell. No significant differences (p greater than .05) were found in the total number of receptors per PMN between the control population (805 +/- 95) and the mild atopic dermatitis patients (745 +/- 91) or the moderate to severe group (621 +/- 79). In addition, no significant differences in receptor affinity were found among any of the 3 study groups. These findings suggest that beta receptor binding in atopic dermatitis is normal. Reduced cyclic AMP generation in atopic dermatitis PMN leukocytes would appear to be due to a defect distal to the beta adrenergic receptor itself.     

Interferon-alpha therapy in atopic dermatitis.

Thirteen patients with a severe adult form of atopic dermatitis (AD) received 3.0 x 10(6) IU of recombinant interferon-alpha 2a (rIFN-alpha 2a) 3 times a week. A satisfactory response was obtained in 5 of them. Serum IgE levels in all 13 patients remained unchanged throughout the study. Flu-like symptoms were common, but clinical or laboratory adverse effects were otherwise slight. The moderately beneficial therapeutic effects observed in this study support a possible role for IFN-alpha in controlling immunologic deficiencies in atopic dermatitis.     

Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor axon reflex test

Summary Background Impaired sweating is thought to be a cause of barrier dysfunction in atopic dermatitis (AD). Objectives To examine the sweating function in AD in a quantitative manner. Methods We investigated the sweating response of lesional and non‐lesional skin of adult patients with AD by a quantitative sudomotor axon reflex test in which the axon reflex is stimulated by acetylcholine iontophoresis. Sweat volume on the volar aspect of the forearm was measured in 18 adult patients with AD and in 40 non‐atopic controls; five patients with Sjögren's syndrome were also studied as disease comparators. We also evaluated the sweating function in four AD patients after topical corticosteroid therapy. Latency time, direct (DIR) sweat volume and axon reflex‐mediated indirect (AXR) sweat volume were the variables studied. Results The latency time in AD patients was significantly prolonged and AXR sweat volume significantly reduced compared with those in non‐atopic control subjects. The latency time and AXR sweat volume of lesional AD skin were significantly more prolonged and reduced, respectively, than those of non‐lesional skin. In contrast, the DIR sweat volume of lesional or non‐lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced when compared with that in non‐atopic controls. Latency time and sweat volumes of lesional and non‐lesional AD skin improved after topical corticosteroid therapy. Conclusions These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is reversed by topical corticosteroid administration.     

Concomitance of psoriasis and atopic dermatitis.

There is a widespread belief that psoriasis (Ps) and atopic dermatitis (AD) are clinically mutually exclusive. A prospective study was undertaken to record the concurrent and/or consecutive coincidence of the two conditions and any shared clinical features. Patients attending a dermatology clinic were systematically examined for the presence of Ps and/or AD. Nine hundred and eighty-three patients were studied--428 with Ps, 224 with AD, 45 with both Ps and AD, and 286 controls. Of AD patients 16.7% had Ps, and 9.5% of Ps patients had AD. In consecutive occurrences, Ps generally followed AD. The ratio of concurrent to consecutive incidences was 3:1. The two diseases are shown not to be mutually exclusive and may coexist in the same individual.     

Adrenaline-induced local sweating and vasoconstrictive responses in atopic skin

Sweating and vasoconstrictive responses to intradermal injections of adrenaline were studied in the normal-looking back skin of young adult males with atopic dermatitis (AD) and in non-atopic controls using five concentrations of adrenaline, and further in a subgroup of subjects with dry-looking AD skin using two concentrations of adrenaline. The sweating responses were measured with an evaporimeter and the area of blanching determined with planimetry. The maximal sweating response in the AD group was elicited with the suprathreshold concentration of 5 x 10(-6) mol/l and in the non-atopic group with a 10-fold higher concentration. At the three higher concentrations the sweat rates levelled out in both groups and remained at a lower level in AD subjects. The sweating responses in dry-looking AD skin were lower than in non-atopics (P less than 0.001) and were also lower than in those with AD normal-looking skin (P less than 0.05) with both concentrations. In contrast to sweating, the vasoconstrictive reactions showed similar dose-dependent increases with all tested concentrations in AD patients with normal-looking skin and in the non-atopic controls. In patients with dry AD skin the vasoconstrictive responses were also similar to those in non-atopic controls.     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996     

Microbial flora of atopic dermatitis.

The microbial flora of dermatitic skin, uninvolved skin, and the anterior nares of subjects with atopic eczema were investigated. The carriage rate of Staphylococcus aureus was 79% for the anterior nares, 76% for the uninvolved skin (normal skin), and 93% for lesions. The counts of S aureus were 7.5 X 10(4)/sq cm in lesions and 7.1 X 10(3)/sq cm on adjacent normal skin. Staphylococcus aureus was the predominant organism in the lesions and constituted 91% of the total aerobic bacterial flora. The coagulase-negative staphylococci were the second predominant organisms (9%). On normal skin, coagulase-negative staphylococci were the predominant organisms, constituting 63% of the total flora, followed by S aureus (30% of the bacterial flora). The micrococci counts were lower in the lesions (1.6 X 10(2)/sq cm) and higher on normal skin (9.5 X 10(2)/sq cm). Lipophilic diphtheroids were fewer on normal skin (6.7 X 10/sq cm), and there were none in the lesions. Fifty-eight percent of the strains belonged to group 3, and 38% were nontypeable. Staphylococcus aureus strains belonging to phage groups 2 and 4 were not detected.     

Effects of adrenergic stimulating and blocking agents on the eccrine sweat secretion in atopic dermatitis and psoriasis

Summary Quantitative measurements of eccrine sweat secretion following stimulation with adrenaline and terbutaline sulphate, a-stimulator, have been performed in patients with atopic dermatitis and psoriasis by means of the electrolytic water analyzer, Meeco. Seasonal variations were demonstrated, the values being lower in the late autumn. The response to adrenaline could be blocked by phentolamine, an -inhibitor, while propranolol, a-inhibitor, had no effect.—The response to terbutaline was blocked by atropine and partly by practolol, a-inhibitor. Terbutaline induced a larger sweat response than isoprenaline, another-stimulator. A-receptor mechanism, in some way related to cholinergic receptors, is suggested.

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Zusammenfassung Die ekkrine Schweißabgabe nach intradermaler Infektion von Adrenalin und Terbutalin sulfat, einem-Stimulator, wurde mittels des elektrolytischen Wasser-Analysators Meeco quantitativ gemessen. Saison-abhängige Variationen wurden festgestellt, wobei eine signifikante Verminderung im Herbst beobachtet wurde. Die adrenalininduzierte Schweißabgabe wurde mittels Phentolamin, einem -Inhibitor, aber nicht mittels Propranolol, einem-Inhibitor, blockiert. — Das Terbutalin-induzierte Schwitzen wurde durch Atropin eindeutig, aber durch Practolol, ein-Inhibitor, nur teilweise blockiert. Terbutalin induzierte eine größere Schweißaktivität als Isoprenalin, ein anderer-Stimulator. Die Resultate deuten auf einen-Receptoren-Mechanismus in den ekkrinen Schweißdrüsen hin, der vielleicht in engem Zusammenhang mit cholinergischen Receptoren steht.

     

角质形成细胞与特应性皮炎相关研究进展

角质形成细胞（keratinocytes,KCs）的异常导致角蛋白的表达出现异常,从而导致表皮屏障功能失调。在特应性皮炎(Atopic Dermatitis,AD)皮损中,KC大量表达胸腺淋巴基质生成素、肿瘤坏死因子α以及一些白细胞介素如IL-1α、IL-1β和IL-18等介导皮肤的炎症反应。在AD中KC还可表达模式识别受体,通过先天免疫系统,产生和维持炎症反应。另外,AD皮损中KC损伤导致抗菌肽的表达缺乏可能有助于增加AD患者皮肤对感染病毒、细菌和真菌的易感性。本文对角质形成细胞与特应性皮炎相关研究进展进行综述。     

Lysozyme in atopic dermatitis

The aim of the present study was to determine the levels of lysozyme in serum and saliva in 10 patients with atopic dermatitis (AD). A significantly decreased lysozyme levels in saliva compared to controls (p less than 0.01) were showed, whereas no differences were found in lysozyme activity in serum of patients and controls. The reduced levels in saliva can hardly be explained. The decreased levels of lysozyme in external fluids may be one explanation for the well-known predisposition for AD patients to an increased susceptibility to many cutaneous infections.     

特应性皮炎的转录组学研究进展

【摘要】 随着基因芯片技术、RNA测序技术等转录组学技术发展,特应性皮炎（AD）发病中重要的相关影响因素逐渐被揭示,如不同T辅助（Th）细胞的亚型以及其他免疫相关细胞如巨噬细胞、朗格汉斯细胞;在AD的瘙痒及皮肤屏障破坏方面,相关免疫细胞如Th2细胞及角质形成细胞等所释放白细胞介素4、白细胞介素13、聚丝蛋白、兜甲蛋白等活性物质的异常变化起着主要作用。同时,转录组技术已被用于分析患者治疗前后转录谱的变化从而对患者的病情和治疗效果进行评估等。本文总结近年来在AD转录组学方面的研究进展。     

Cromones in atopic dermatitis

Summary Three new cromones have been studied that are supposed to be better absorbed and to have a wider spectrum of anti-allergic activity than disodium cromoglycate. Pretreatment with i.d. injection of 10 g FPL 52758 significantly reduced the weal and flare reaction induced by specific antigen in 11 patients with atopic dermatitis. The weal and flare reaction was not reduced in the same patients when 1.5 mg of FPL 52758 was applied topically under occulusion for a 24-h period prior to challenge with antigen. The itch and slight pain caused by antigen injection was not experienced in the FPL 52758 pretreated areas.Preliminary clinical results were obtained with the cromone FPL 52757, but due to possible hepatotoxicity this trial was not completed. Another similar cromone without hepatotoxicity was used in a double blind within-patient study. Nine patients with mild to moderate atopic dermatitis were treated with FPL 57787 (5%) ointment and matching placebo ointment. No significant improvement was observed after 4 weeks of treatment with the cromone containing ointment.     

Diet and atopic dermatitis

Prevention or modification of the onset of atopic dermatitis has been difficult to document through prolonged breast feeding or delayed introduction of solid foods. Dietary management of established atopic dermatitis is not routinely indicated for the majority of patients. Dietary management of atopic dermatitis should not be continued indefinitely. Gradual reintroduction of the offending food(s) is often appropriate. The foods most commonly avoided in the management of atopic dermatitis are cow's milk, wheat, eggs, and nuts. Severe or prolonged dietary restrictions should not be instituted without full consideration of their impact on the patient's general health.     

Urticaria in atopic dermatitis

During examinations of 479 patients referred for atopic dermatitis and 520 with urticaria it was found that in the first group coexistence of these diseases was frequently occurring, and in the second group it was rare. Food allergens caused slightly more frequently episodes of urticaria than exacerbations of atopic dermatitis. Coexistence of urticaria with atopic dermatitis was particularly frequent in patients: a) with a high IgE titre, b) with a history of allergy in the families of both parents, c) in patients with respiratory allergy associated with skin lesions.     

Biologics in atopic dermatitis

Atopic dermatitis (AD) accounts for a significant share of chronic inflammatory skin disorders. There is a niche for the development of biologics to treat recalcitrant autoinflammatory stage AD seen mostly in adults. The heterogeneity of patient response to various existing biotherapies points to involvement of various immune responses and suggests that therapies must preferably target early development of allergen‐specific B‐ and T‐cell clones. In addition to immune targets, tissue factors that help restore the normal epidermal environment constitute interesting therapeutic tools. Several approaches are needed to find the appropriate targets in a field where so many have been investigated without definitive proof of concept for human systemic therapy. The keys to success are probably (1) to influence the inflammatory skin pattern towards less pruritogenic effects, requiring us to better understand pruritogenic inflammation and (2) to limit the amplification loop of disease by attacking abnormal regulatory mechanisms which perpetuate skin autoinflammation.