Immunohistochemical studies in mite antigen-induced patch test sites in atopic dermatitis

The role of mite allergen in atopic dermatitis is still unclear. In this study, we investigated whether an eczematous reaction could be induced by patch testing with dust mite antigen. We succeeded in reproducing an eczematous lesion and the mite RAST-positive AD group showed a positive reaction much more than the RAST-negative group. Many mite antigen-bearing Langerhans cells, also possessing IgE molecules, were found by the use of an immuno-double labelling technique. By using immunoelectron microscopy, it was observed that the mite antigens were trapped by some macrophages, which were apposed to lymphocytes. To investigate the time-course of the reaction, the patch test reactions were read and biopsied after 1 h, 6 h, 24 h and 48 h. An eczematous reaction developed 24 h after patch testing. The mite antigen-bearing Langerhans cells were seen exclusively in the epidermis after 6 h, and mainly in the dermis after 24 h and 48 h. These results suggested that IgE-mediated contact hypersensitivity to mite antigen may develop and play an important role in AD.     

Some neuropeptides as modulators of experimental contact allergy

The role of some peptides in allergic contact dermatitis was investigated. The neuropeptides: substance P (SP), vasoactivc intestinal peptide (VIP) and somatostatin as well as the SP antagonist. Spantide, were injected into the same skin sites is the antigen in patients with contact allergy to nickel. The neuropeptides did not influence the eczematous reaction but spantide diminished it. This might speak for a pathogenetic role of SP in allergic, contact dermatitis.     

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%.     

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.     

A study of the role of house dust mite in atopic dermatitis

Subjects with positive skin-prick tests to house dust mite (HDM) solution, including those with and without atopic dermatitis, participated in a double-blind, controlled study of the role of HDM exposure in the pathogenesis of atopic dermatitis. HDM solution and diluent control were applied daily to mildly eczematous or clinically uninvolved skin of the antecubital or popliteal fossae, without prior abrasion, for 5 days. Responses were assessed by a clinical grading system and by measurement of area of dermatitis; pruritus was recorded on visual analogue scales. The clinical grading system showed that marked or moderate delayed local reactions developed in one third of patients with atopic dermatitis in response to HDM application to both mildly eczematous and clinically uninvolved skin. Relative to control sites, significant increases in area of dermatitis and degree of pruritus were also recorded in response to HDM application to mildly eczematous sites. Application of HDM solution to normal, unabraded skin of prick test positive subjects without a history of dermatitis, produced pruritus and immediate urticarial responses which were not seen at control sites, findings which demonstrate that HDM antigen may be rapidly absorbed in normal skin. Application of vehicle or antigen solution to which subjects were negative on prick testing, produced no significant local reactions. This study provides objective evidence for a role for cutaneous HDM exposure in the pathogenesis of atopic dermatitis.     

Familial background of respiratory atopy. A factor of type I allergy to house dust mite in patients with atopic dermatitis

Skin prick and radioallergosorbent tests with the house dust mite were performed in 120 patients with atopic dermatitis. The results showed that about 60% of the patients had type I allergy to the mite. Results of the prick and radioallergosorbent tests did not relate to the severity of skin involvement, nor to the seasonal fluctuation of the disease. Positive skin and radioallergosorbent tests occurred in many patients with atopic dermatitis who had a personal or family history of respiratory atopy. However, both of these tests were negative in the majority of patients with "pure" atopic dermatitis who had neither a personal nor a family history of respiratory atopy. It was suggested that a familial background of respiratory atopy is an important factor for the development of type I allergy to the house dust mite in patients with atopic dermatitis.     

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.     

Hypersensitivity to bacteria in eczema

A study was made of the cytotoxic effect of antibacterial antibody and complement reacting with bacterial antigens firmly adsorbed to epidermal cells. It is believed that this phenomenon enhances the severity of the lesions and their spread in some cases of disseminated eczema. In this first part of the study it is confirmed that Staphylococcus aureus and micrococci are frequently present on lesions and 'unaffected' skin of patients with disseminated eczema. Intradermal skin tests with antigens of staphylococci and micrococci on 122 eczematous patients elicited immediate, or combined immediate and 4 h (Arthus-like) responses, in a large proportion, but few showed uncombined 4 h responses or delayed hypersensitivity, in contrast to findings reported by others. Immunofluorescence tests on skin of thirty patients showed that IgG and IgM diffused into the epidermis, sometimes to the skin surface, of lesional skin, and more immunoglobulin was found in skin of 'unaffected' areas than in skin of normal healthy persons, indicating that clinically unaffected skin in patients with disseminated eczema is abnormal. IgD was present in three of eight samples of unfixed, and six of eight samples of fixed eczematous skin. Staphylococcal and micrococcal antigen was shown on the skin surface and also diffusely in the cytoplasm of cells in the dermis beneath the surface deposits, indicating percutaneous absorption. Further small amounts of antigen were adsorbed to some epidermal cells. These results show that the predisposing conditions for a cytotoxic reaction mediated by hypersensitivity to bacteria do occur. Increased growth of staphylococci and micrococci on eczematous skin would result in increased deposits of antigen. Bacterial antigens are absorbed into the skin and bind with epidermal cells, and immunoglobulins diffuse into the epidermis. Furthermore, skin tests showed that many eczematous patients were hypersensitive to bacteria. Studies on the nature of the antibacterial antibody will be published in the succeeding reports.     

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.     

Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain

Atopic eczema is often worsened by stress. While acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT), chronic stress causes a decrease. In chronic stress, there is a decrease of the 5-HT1A receptor (R)- and an increase in the 5-HT2AR-responsiveness to 5-HT. In the present study, the impact of chronic mild stress on the expression of 5-HT1A and 5-HT2A receptors and serotonin transporter protein (SERT) was investigated in eczematous skin and brain of atopic-like NC/Nga mice. Twenty-four NC/Nga mice were subjected to chronic mild stress for 12 weeks, and eczema was induced by applying a mite antigen (Dermatophagoides pteronyssinus) on the ears for the last 4 weeks. The mice were divided into three groups, eight per group, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC). The biopsies were analysed by immunohistochemistry, using a streptavidin–biotin technique. There was an increased number of 5-HT containing dermal mast cell-like mononuclear cells in the skin of mice with eczema (SE and NSE, respectively) compared with the SC, and a tendency to more 5-HT-positive cells in the SE compared with the NSE group. Increased 5-HT1AR immunoreactivity (IR) in the skin and hippocampus of the eczematous groups compared to the control group was seen, but no difference between the SE and NSE groups. The epidermal immunoreactivity for 5-HT2AR was highest in the SE and NSE compared to the SC group, and was also higher in the SE compared to NSE. 5-HT2AR expression was also seen on nerve bundles, the number and intensity of such bundles being decreased in the SE compared to the NSE group. In the CA1 area of the hippocampus, there was an increase in the quantity of cells immunoreactive for 5-HT2AR in the SE versus the NSE group and also in the SE versus the SC group. SERT-IR was found also on nerve bundles with a decreased number in the SE compared to the NSE and SC group. There is a modulation of the expression of serotonergic markers in the eczematous skin and brain of the atopic-like mouse during chronic mild stress.     

Occupational airborne contact allergy to tetrazepam in a geriatric nurse

A 52‐year‐old geriatric nurse presented with recurrent eczema localized in uncovered skin areas. Patch testing produced an eczematous skin reaction with type IV sensitization to tetrazepam. A relapse of contact dermatitis was successfully prevented by using occupational skin protection measures and organizational measures. Our case indicates that a sensitization to drugs should be considered when allergic contact dermatitis is suspected in nursing personnel.     

Delayed contact allergies in patients with photosensitivity dermatitis

Delayed contact allergies and the clinical course of the skin disease were investigated in 14 patients with photosensitivity dermatitis/actinic reticuloid and 145 patients with polymorphous light eruption type eczema. Hypersensitivity to chromium and rubber chemicals was encountered in photosensitivity dermatitis more often than in polymorphous light eruption eczema and in the comparison series of 1714 patients with other types of dermatitis. In the eczema group, delayed contact allergies to chromium, rubber chemicals, neomycin, clioquinol, balsam of Peru, fragrance and colophonium were more frequent than in the comparison group, suggesting that at least delayed contact allergy to chromium and rubber chemicals may be of significance in the development of photosensitivity in many patients who suffer eczematous reaction to sunlight.     

Aminoethylethanolamine: a new allergen in cosmetics?

Amphoacetates are organic compounds used in many industrial applications and in cosmetic formulations for the skin, hair and mucosa, as surfactants, mild foaming and cleansing agents in concentrations ranging from 0.1% to 50%. Despite the fact that they have been in use for many years, cases of contact allergy to them are extremely rare. We describe 4 patients who developed an eczematous reaction after use of detergents containing amphoacetates. Patch testing showed positive reactions to sodium lauroamphoacetate (Miranol HM Special, Rhodia, England) as is or diluted at decreasing concentration (10%, 5% and 1%) in water and to aminoethylethanolamine (AEE) at the concentration of 1% in various vehicles (ethanol, acetone, and sodium laurylethersulfate 1% aqueous solution) and at decreasing concentrations ranging from 1% to 0.005% in water. AEE is one of the reagents used in the synthesis of amphoacetates. This molecule, that is structurally an ethylenediamine derivative, has sensitizing power and is reported as a cause of occupational contact allergy in cable jointers. Combined eczematous reactions to AEE and sodium lauroamphoacetate can be consequent to the presence of the former substance as an impurity in amphoacetates-containing products, as demonstrated by ion chromatography-mass spectrometry analysis.     

Thermographic analysis of skin test reaction using AGA thermovision

The course of infrared thermography including isothermograms on the skin surface was investigated considering blood flow, redness of the skin and permeability of blood vessel, in the following skin reactions: 1. Intracutaneous injection of histamine and histamine liberator compound 48/80 increased the heat radiation. Local application of antihistamine externa which decreased the development of the urticarial histamine reaction, increased the infrared radiation of the skin surface. Combined injection of histamine or histamine liberators with antihistamines in a sufficient dosis (1:1 respectively 4:1) diminished also the heat radiation in addition to the urticarial reaction. 2. The Pyrexal reaction of the skin with early erythema and later papule development shows an equivalent picture in the AGA Thermovision. The pretreatment shows an equivalent picture in the AGA Thermovision. The pretreatment of the skin with corticosteroid ointments shows a corresponding lowering of the erythema, of papule development as well as of heat radiation. The blanching of corticosteroids after occlusive dressing is difficult to recognize by the isotherms of AGA Thermovision. 3. Allergic reactions of the immediate type show, corresponding to the wheal eruption, a marked increased of heat radiation combined with a projection of the enlarged veins on the skin surface. 4. Allergic reactions of the delayed type are combined with a definite elevation of heat radiation of the skin. The area of a positive skin test with allergic eczematous reaction shows a distinct elevation of ann infrared radiation. Although the allergic skin area which was substantiated by a positive skin test was no longer visible, a distinct infrared radiation could be detected. Preventive treatment of the test area of skin patch-testing with corticosteroids inhibits the heat radiation even if the allergic eczematous reaction occurs faintly. The thermographic analysis of the different skin test reactions complied with the morphological aspects of the reaction.     

Flare factors and atopic dermatitis: the role of allergy

Atopic dermatitis is a genetically determined eczematous skin disease strongly influenced by environmental conditions called flare factors. Allergic reactions are one such flare factor. These reactions include contact urticaria, allergic contact dermatitis, and late phase reactions. Contact urticaria could induce eczema by eliciting scratching. A late phase reaction may be involved in eczema produced by prolonged epicutaneous applications of antigens in individuals with immediate sensitivity to these antigens. Mechanisms of allergic contact dermatitis might also elicit dermatitis. Environmental allergens may include mold, dust, mite, pollens, foods, danders and bacteria.     

食物过敏与儿童特应性皮炎相关性及其诊断

大约1/3中到重度特应性皮炎患儿存在食物过敏,但食物过敏是否会诱发或加重特应性皮炎患儿的湿疹样皮损仍存在争议.食物过敏可以诱发特应性皮炎患儿的两种反应,非湿疹样反应和湿疹样反应.前者为IgE介导,诊断相对比较简单,多数情况下借助病史、皮肤点刺试验及特异性IgE抗体水平等即可明确诊断.后者为细胞介导,诊断必须借助口服食物激发试验.如果没有条件做食物激发试验时,也可以借助诊断性的饮食回避来明确可疑过敏食物.     

食物过敏与儿童特应性皮炎相关性及其诊断

大约1/3中到重度特应性皮炎患儿存在食物过敏,但食物过敏是否会诱发或加重特应性皮炎患儿的湿疹样皮损仍存在争议.食物过敏可以诱发特应性皮炎患儿的两种反应,非湿疹样反应和湿疹样反应.前者为IgE介导,诊断相对比较简单,多数情况下借助病史、皮肤点刺试验及特异性IgE抗体水平等即可明确诊断.后者为细胞介导,诊断必须借助口服食物激发试验.如果没有条件做食物激发试验时,也可以借助诊断性的饮食回避来明确可疑过敏食物.     

Clinical response to gold as a circulating contact allergen

In order to study the flare-up of contact allergy, 35 patients with a contact allergy to gold were given an intramuscular injection of 10 mg gold sodium thiomalate, i.e. the anti-rheumatic drug Myocrisin. Clinical reactions comprised an eczematous flare-up of previously positive patch tests to gold and of a previous dermatitis, which occurred in 80% and 26%, respectively; a toxicoderma-like rash in 46%; and a transient fever in 60%. With the antigen rapidly reaching the bloodstream, the technique provides an experimental human model for studying flare-up mechanisms in contact allergy.     

Immunologie der Kontaktallergie

Contact allergy is a skin disease that is caused by the reaction of the immune system to low molecular weight chemicals. A hallmark of contact allergens is their chemical reactivity, which is not exhibited by toxic irritants. Covalent binding of contact allergens to or complex formation with proteins is essential for the activation of the immune system. As a consequence antigenic epitopes are formed, which are recognized by contact allergen-specific T cells. The generation of effector and memory T cells causes the high antigen specificity and the repeated antigen-specific skin reaction of contact allergy. New findings reveal that the less specific reaction of the innate immune system to contact allergens closely resembles the reaction to an infection. Therefore, contact allergy can be viewed as an immunologic misunderstanding since the skin contact with chemical allergens is interpreted as an infection. The growing understanding of the molecular and cellular pathologic mechanisms of contact allergy can aid the development of specific therapies and of in vitro alternatives to animal testing for the identification of contact allergens.     

Immunophenotyping of the eczematous flare-up reaction in a nickel-sensitive subject

An eczematous flare-up reaction, occurring at a previously involved site, which followed oral challenge with 5.6 mg of nickel in a 29-year-old nickel-sensitive woman, was biopsied and studied by immunohistochemistry. The cellular infiltrate in the dermis and epidermis at 8 days was predominantly of Leu 3a phenotype (helper/inducer T lymphocytes), with smaller numbers of Leu-2a-reactive (suppressor/cytotoxic) T lymphocytes. Many infiltrating cells were DR-positive. No increase in epidermal Leu-6-positive Langerhans cells was seen but Leu-6-reactive cells were noted in the dermal infiltrate. Keratinocytes showed some expression of class II antigen (mainly DR). In comparison with the 48-hour allergic patch test reaction, the eczematous flare-up site showed no increase in epidermal Langerhans cell numbers nor infiltration with macrophages, but the responses were similar since both showed a superficial T cell reaction in the skin.