House dust mite (HDM) antigen in naturally occurring lesions of atopic dermatitis (AD): the relationship between HDM antigen in the skin and HDM antigen-specific IgE antibody.

To elucidate the etiological role of house dust mite (HDM) antigen in the pathogenesis of atopic dermatitis (AD), we conducted immunohistochemical studies on the localization of HDM antigen in naturally occurring lesions of AD. HDM antigens were found in the epidermis and dermis in 19 of 38 cases. All of the 19 patients had HDM antigen-specific IgE antibody, but HDM antigen was not detected in the lesions of patients without HDM antigen-specific IgE or in control skin specimens. Most HDM antigens were located on Langerhans cells (LCs) or near helper T cells. Our findings suggest that HDM antigen is the causative factor in the development of eczematous lesions of AD, and thus we hypothesized that IgE-mediated allergic contact sensitivity to HDM antigen plays an important role in the pathogenesis of AD.     

The role of photochemotherapy (PUVA) in the treatment of children with severe atopic dermatitis and short stature

The significance of reports^1,2, that topical application of house dust mite (HDM) to abraded or excoriated uninvolved skin of patients with atopic eczema can provoke an eczema-like reaction is controversial. We have therefore studied 17 adult in-patients with atopic eczema who demonstrated positive prick tests to Bencard HDM solution. One ml of Bencard HDM solution was applied, under a crepe bandage, daily for 5 days to an untreated 10 cm² mildly eczematous area behind one knee, and diluent only, similarly, to the other knee in a double-blind fashion. Test sites were assessed daily for itch using a visual analogue scale and for severity of erythema, papules and excoriation using a 3-point grading system. Comparing these parameters between active and control sites for each patient, local worsening of eczema in response to HDM was marked in 5/17, moderate in 3/17 and mild in 4/17 subjects, while mild deterioration with diluent only occurred in 3/17. Mean area of active eczema increased by 6 26 ± 8 4 cm² (± SD) at HDM-treated and by 0 5 ±1.5 cm² at control sites (P≤0.01; paired t -test). Further patients exposed to Bencard horse hair extract, to which they were prick-test negative, in place of HDM, showed no reaction. These results indicate that HDM can exacerbate pre-existing atopic eczema.     

Cyclosporin A in atopic dermatitis: therapeutic resonse is disociated form effects on allergic reactons

Fourteen patients with severe chronic atopic dermatitis were treated with cyclosporin A (CyA, Sandimmun; 5 mg/kg/day) for 7-16 weeks. All showed a marked clinical improvement and half could omit topical corticosteroid treatment during therapy. Adverse effects were minor, but two patients relapsed despite continued treatment. In the others, the disease recurred soon after stopping CyA. Serum IgE levels and prick-test responses were unchanged by CyA. Immediate and late-phase cutaneous responses to intradermal house dust mite antigen (HDM) were significantly increased during treatment; but a delayed response, present at 24 and 48 h, was unaffected. Four of six patients challenged with HDM patch tests to tape-stripped skin during treatment showed eczematous reactions at 48 h. Thus, cyclosporin A has a powerful therapeutic effect in atopic dermatitis but does not reduce allergic responses to inhalant antigens.     

Eczematous Skin Reaction from Patch Testing with Aeroallergens in Atopic Children With and Without Atopic Dermatitis

Abstract: To determine whether aeroaltergens could induce eczematous lesions, 30 patients with atopic dermatitis were studied in comparison with 30 patients with respiratory atopy without atopic dermatitis. All patients were between 2 end 14 years of age. Patch testing with five aeroallergens—housedust, mite, cockroach, mold mix, and grass mixwas done on skin that was stripped by 10 applications of adhesive tape. Intradermal tests with the same antigens were done on the forearm. In 27 (90%) children with staple dermatitis, patch testing with aeroallergens Induced eczematous lesions at one or more sites. Mite, cockroach, house dust, mold mix, and grass mix caused reactions In 21 (70%), 21 (70%), 19 (63%), 15 (50%), and 13 (43%) patients, respectively. Three patients had a dermatitis flare at the antecubital and popliteal fossae during testing. Only three (10%) atopic children without atopic dermatitis had eczematous lesions, which was significantly different from children with atopic dermatitis ( P < 10⁻⁵). Intradermai skin tests in both groups were not significantly different This study supports previous reports that aeroallergens play an Important role in causing eczamatous skin lesions.     

The characteristics of patients with atopic dermatitis demonstrating a positive reaction in a scratch test after 48 hours against house dust mite antigen

The clinical characteristics of patients in whom an IgE-mediated reaction against house dust mite (HDM) antigens that contribute to the pathogenesis of atopic dermatitis (AD) remain unclear. This study attempted to elucidate the characteristics of patients who exhibit a positive reaction 48 hr or later against HDM in scratch tests. The reactions after epi-cutaneous application of the allergen to skin with prior scratching were observed for one week in sixteen AD patients showing positive immediate-type hypersensitivity reactions for HDM. Fifty percent of the patients demonstrated positive reactions at 48 hours after epi-cutaneous application of HDM. Significantly higher values were demonstrated in the group positive for HDM after 48 h in serum total IgE, specific IgE for Der f 1, and lactate dehydrogenase, peripheral eosinophil counts, eruption score, and the area of eruption than in the group negative for HDM after 48 h. Domestic exposure to Der f 1 was also higher in the group positive for HDM after 48 h than in the negative group. These results indicate that the patients in whom the HDM-induced reaction continuing more than 48 h and contributing to their real eczematous eruptions are characterized by considerably increased levels of specific IgE for HDM antigens, high disease activity in AD, and increased exposure to domestic HDM.     

中国特应性皮炎诊疗指南（2020版）

【摘要】 特应性皮炎以反复发作的慢性湿疹样皮疹为主要表现，伴有显著的皮肤干燥和瘙痒。随着生活方式和环境的改变，近10余年间我国特应性皮炎的发病率不断升高，受累及的人群涉及各年龄段。本指南结合近5年特应性皮炎的研究进展，在2014版中国特应性皮炎诊疗指南的基础上予以进一步的补充和完善，对特应性皮炎的定义、患病率、发病机制、分类、诊断、预防和治疗进行更新，可为特应性皮炎的诊疗提供科学和权威的参考依据。     

The relationship between eosinophils, OKT6-positive cells and house dust mite (HDM) antigens in naturally occurring lesions of atopic dermatitis.

To determine the role of eosinophils in naturally occurring lesions of atopic dermatitis, we observed the distribution of eosinophil cationic protein (ECP) and the relationship between eosinophils, OKT6-positive cells and house dust mite (HDM) antigens. Some specimens showed many EG2-positive stains, although the accumulation of tissue eosinophils was not prominent. EG2 stains were seen not only in eosinophils but also in extracellular granules. Some macrophage-like cells of the dermis showed EG2 stains in the form of phagocytized eosinophil granules. Some EG2-positive eosinophils were in close contact with OKT6-positive cells in the epidermis and dermis. Furthermore, in three patients sensitive to house dust mite (HDM) antigen, HDM antigens invaded the skin with many EG2-positive stains. These results suggest that eosinophils play an active role in the development of eczematous lesions of atopic dermatitis.     

Eosinophil cationic protein in sera of patients with atopic dermatitis

Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergic reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p less than or equal to 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p less than or equal to 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant allergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy.     

Does food allergy cause atopic dermatitis? Food challenge testing to dissociate eczematous from immediate reactions

The objective is to evaluate and diagnose, in a controlled setting, suspected food allergy causation in patients hospitalized for management of severe, unremitting atopic dermatitis (AD). Nineteen children were hospitalized at Oregon Health and Science University with atopic dermatitis from 1986 to 2003 for food restriction, then challenge, following standard recommendations. Challenges were prioritized by categories of (a) critical foods (e.g., milk, wheat, egg, soy); (b) important foods; and (c) other suspected foods. Patients were closely observed for evidence of pruritus, eczematous responses, or IgE-mediated reactions. If results were inconsistent, double-blind, placebo-controlled food challenge was performed. A total of 17 children with atopic dermatitis were assessed. Two could not be fully evaluated, thus were excluded from data tabulations. Only one positive eczematous food response was observed of 58 challenges. Three children had well-documented histories of food-induced IgE-mediated anaphylactoid or urticaria reactions to seafood and/or nuts and were not challenged with those foods. Atopic dermatitis, even in the highest-risk patients, is rarely induced by foods. Undocumented assumptions of food causation detract from proper anti-inflammatory management and should be discouraged. Immediate IgE-mediated food reactions are common in atopic dermatitis patients; such reactions are rapid onset, typically detected outside the clinic, and must be distinguished from eczematous reactions. Diagnosis of food-induced eczema cannot be made without food challenge testing. Such tests can be practical and useful for dispelling unrealistic assumptions about food allergy causation of atopic dermatitis.     

The morphologic characteristics of dry skin in atopic dermatitis

Uninvolved skin sites in 436 consecutive patients, 6 to 25 years old, with atopic dermatitis were observed during the winter months (from November to February). Ichthyosis vulgaris occurred in 133 patients. Of the 303 remaining patients, only 11 (4%) had generalized dry skin; 191 (63%) exhibited focal areas of dry skin; and 95 (33%) showed only normal-appearing skin. Microscopically, in 41 patients, dry skin associated with atopic dermatitis showed mild eczematous changes. Dry skin coexistent with ichthyosis in patients with atopic dermatitis revealed ichthyotic changes frequently superimposed on eczematous changes. We suggest that in patients with atopic dermatitis the presence of dry skin may reflect mild eczematous changes, a manifestation of concomitant ichthyosis, or a complex of both of these changes.     

Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of atopy patch testing and histological examination

Atopy patch testing with Japanese cedar pollen extract has been used to investigate patients with atopic dermatitis whose condition is exacerbated by contact with Japanese cedar pollen. Comparative atopy patch testing, scratch tests, and assays for total IgE and specific IgE were performed in 74 patients with atopic dermatitis, 5 patients with Japanese cedar pollinosis and 15 control subjects. A skin biopsy was performed on any sites that were positive to Japanese cedar pollen patch test. The results after 48 h of atopy patch testing were compared with the patient's history, skin scratch test and specific IgE. Twenty-two of the 74 patients (30%) had a history of exacerbation every spring after contact with Japanese cedar. Of these patients 68% showed a positive reaction to Japanese cedar pollen extract, as did 21% of patients with atopic dermatitis without a history of exacerbation by Japanese cedar pollen, 20% of patients with Japanese cedar pollinosis without eruption and 7% of control subjects. A histological examination revealed eczematous changes and infiltration of lymphocytes and eosinophils in atopy patch testing positive sites. In conclusion, atopy patch testing with Japanese cedar pollen extract is a useful method for investigating trigger factors for eczematous skin lesions in a subgroup of patients with atopic dermatitis.     

Increase in skin mast cells following chronic house dust mite exposure

Application of inhalant allergens in high concentration to the mildly abraded skin of sensitive patients with atopic dermatitis gave rise to eczematous skin responses at 48 h. These lesions, infiltrated by basophils, eosinophils and mononuclear cells, are examples of cutaneous basophil hypersensitivity. Repeated application of allergen induced an increase in skin mast cells by 6 days, the mast cell hyperplasia replacing the earlier basophil infiltration. No electron microscopic evidence of mast cell heterogeneity among the recruited cells was found.     

Chronic actinic dermatitis. Concept and case examples]

Two women patients with chronic eczematous dermatitis, who also developed extremely severe, persistent photosensitivity during a course of 10 and over 40 years, are presented. Both patients had an atopic history with positive immediate skin reactions. Patch and photopatch tests revealed sensitization to several contact allergens, and in one case also a photocontact allergy. The action spectrum of the photosensitivity was confined to UV-B; it was possible to provoke eczematous skin reactions with doses smaller than 1 mJ/cm2 UV-B. Both patients were successfully treated with PUVA therapy. These case reports demonstrate the difficulty of nosological classification of chronic eczematous photosensitive dermatoses under the traditional terms persistent light reaction, photosensitive eczema, photosensitivity dermatitis, and actinic reticuloid. Chronic actinic dermatitis is defined clinically by chronic dermatitis on skin exposed to sun, histologically by spongiotic dermatitis, and photobiologically by experimental provocation of spongiotic dermatitis with UV-B and often also longer wavelengths in the absence of a photoallergen. Chronic actinic dermatitis should be used as a general term in addition to the more specific terms listed above.     

Patch tests with house dust mite antigens in atopic dermatitis patients: methodological problems.

Patch tests with house dust mite allergens were performed in 21 atopic dermatitis patients with a positive prick test and RAST for house dust mite. Variables in methodology of patch testing, i.e. allergen concentration, application time, and intensity of tape stripping, were studied. Tests were performed with Dermatophagoides pteronyssinus solutions containing 20X, 100X and 500X the prick test concentration and purified HDM antigen: 10 and 50 micrograms/ml P1Ag solution. The series was applied on 8X or 15X tape-stripped and clinically normal skin on the back during 24 and 48 h. Non-specific reactions due to tape stripping, fixation tape or patch test occlusion were frequently observed: after 15X tape-stripping in 3/7 (24-h application) and 6/7 (48-h application) patients, after 8X tape-stripping in 2/19 (24-h application) and 8/19 (48-h application) patients. Reactions clinically assessed as specific occurred in 6/21 (29%) atopic dermatitis patients, 4/6 occurring in the 10 patients with a serum IgE greater than 1000 kU/l. High allergen concentrations and 48 h of application increased the number of patients with specific reactions. If 15X tape-stripping had been omitted, 2/3 patients tested in this manner and showing specific test reactions would have been negative. Further conclusions regarding the value and the preferable method of patch testing with atopic allergens require an in vitro control test.     

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.     

Water sorption-desorption test and moisture accumulation test for functional assessment of atopic skin in children

Sorption-desorption and moisture accumulation tests are simple and quick methods for the in vivo functional analysis of stratum corneum hydration kinetics. The aim of this study was to evaluate the hydration dynamics of the uninvolved and affected skin of children with atopic dermatitis and to compare them with the skin of healthy children. The study investigated 45 children. The dynamic tests were performed using the corneometer CM820. Numerical parameters were calculated. With the sorption-desorption test, eczematous skin showed lower water accumulation during the sorption phase, whereas water was released more slowly during the desorption phase. With the moisture accumulation test, increases in water accumulation velocity and in water accumulation were observed in atopic children. Dynamic tests showed that the stratum corneum of unaffected atopic skin was less hydrated but more easily hydratable than normal skin. Conversely, despite a lower absorption capability, eczematous skin showed a greater avidity to retain water. New functional parameters (water-sorption capacity and accumulated water decay) are proposed to describe more precisely the hydration kinetics of eczematous skin.     

Eczema herpeticatum

Eczema herpeticum is an acute, disseminated herpes simplex virus infection which remains a feared complication of eczematous skin diseases, especially atopic dermatitis. The vesicular and erosive clinical picture is often accompanied by systemic signs and symptoms. Why some atopic patients experience multiple attacks of eczema herpeticum and others never have the disorder remains a mystery. Patients with severe or untreated atopic dermatitis are more likely to be affected. The pathogenesis appears to involve a complex interplay of factors, including demasking of binding sites for the virus through the dermatitis, failure to up-regulate antiviral proteins and a lack of plasmacytoid dendritic cells. Treatment of choice is systemic acyclovir therapy.     

【开放获取】度普利尤单抗治疗特应性皮炎专家共识

【摘要】 特应性皮炎是一种常见的慢性炎症性皮肤病,以湿疹样皮疹和剧烈瘙痒为主要表现,可严重影响患者生活质量。中重度特应性皮炎往往需要系统治疗,传统的系统治疗对部分患者效果不佳或不能耐受。近年来,生物制剂开始用于临床治疗特应性皮炎,其中白细胞介素4受体拮抗剂度普利尤单抗已经在我国上市。中华医学会皮肤性病学分会特应性皮炎研究中心、中华医学会皮肤性病学分会儿童学组组织本领域部分专家讨论度普利尤单抗在中重度特应性皮炎治疗中的应用,并形成共识,希望本共识能为我国皮肤科医生临床应用度普利尤单抗治疗特应性皮炎提供参考。     

Eczematous reactions in atopic patients caused by epicutaneous testing with inhalant allergens

To determine whether inhalant allergens could induce eczematous lesions we studied 17 patients with atopic eczema (with or without allergic rhinitis), 13 patients with allergic rhinitis without atopic eczema and 10 healthy control subjects. The allergens, birch pollen (Betula verrucosa) and house dust mite (Dermatophagoides pteronyssinus), were applied in aluminium chambers for 48 h on clinically normal skin. In 17 patients with atopic eczema, six epicutaneous test reactions of the delayed type to birch pollen and three to house dust mite were seen at 48 or 72 h. In 13 patients with allergic rhinitis without eczema there was one delayed reaction to birch pollen and none to house dust mite. No delayed type test reactions to either allergen were seen in the controls. Biopsies of the positive test sites revealed an eczematous reaction with epidermal spongiosis and microvesiculation. Immunostaining of cryostat sections showed dermal cell infiltrates consisting of mainly T lymphocytes (ratio of T4:T8, 2-6:I) and to a lesser degree Langerhans and indeterminate T6+ cells. 50-90% of the cells were Ia+. The numbers of basophils and mast cells did not exceed 10-15%.     

Treatment of Patients with Refractory Atopic Dermatitis Sensitized to House Dust Mites by Using Sublingual Allergen Immunotherapy

Even though atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, its treatment remains a challenge in clinical practice, with most approaches limited to symptomatic, unspecific anti-inflammatory, or immunosuppressive treatments. Many studies have shown AD to have multiple causes that activate complex immunological and inflammatory pathways. However, aeroallergens, and especially the house dust mite (HDM), play a relevant role in the elicitation or exacerbation of eczematous lesions in many AD patients. Accordingly, allergen-specific immunotherapy has been used in AD patients with the aim of redirecting inappropriate immune responses. Here, we report three cases of refractory AD sensitized to HDM who were treated with sublingual immunotherapy.