Clinical Significance of Skin Reactions to Mite Extracts in Children with Asthma

The mite Dermatophagoides pteronyssinus has been identified in dust from the houses of children in Birmingham suffering from asthma. Skin tests were carried out on 150 asthmatic children with extracts of D. pteronyssinus, of the related species D. farinae, of other mites found in house dust, and of crude house dust. Though positive reactions to D. pteronyssinus were obtained more frequently and were of greater size than those to the other extracts, it was considered that D. farinae is a suitable substitute for D. pteronyssinus for skin testing.In further tests on 302 asthmatic children with mite extracts and with extracts of allergens obtained commercially reactions to the former extracts were much more common than reactions to the latter.Major skin reactions (weals with diameter of 5 mm. or more) were present in 77% of children with a history of perennial asthma and house-dust sensitivity. Hence allergy to house-dust mites, particularly D. pteronyssinus, is of considerable importance in childhood asthma, and further study of the ecology and control of the mites in dust is desirable.     

Delayed hypersensitivity to house dust-storage mites Thyrophagus putrescentiae in experimental allergic dermatoses]

House dust mites and storage mites proved to be one of the main allergens causing hypersensitivity in atopic dermatitis in allergic patients. The authors reproduced experimental allergic dermatosis on the model of delayed type hypersensitivity in guinea pigs, caused by sensitization to the allergen from the mite's bodies Tyrophagus putrescentiae--species having wide distribution in the country. The results characteristic for T-cell type hypersensitivity have been obtained: delayed positive skin tests after 24 hours, typical histomorphological picture (strong allergic alteration, epidermis desquamation, vasculitis, dermis T-cell infiltration and spongiosis--Waksman's syndrome). It is concluded that side by side with humoral IgE-mediated reaction there is strong delayed T-cell hypersensitivity to the storage mites Tyrophagus putrescentiae.     

The determination of allergen-specific IgE and IgG antibodies in patients sensitized to the house dust mite Dermatophagoides pteronyssinus

45 patients, hypersensitive to house-dust mites, were examined by the method of skin tests to D. pteronyssinus allergen. Besides, in their blood sera the levels of allergen-specific IgE antibodies were determined in the radioallergosorbent test and allergen-specific IgG antibodies, in the enzyme immunoassay. These tests revealed that in 91% of the patients the results of skin tests were positive, in 68% an elevated level of specific IgE antibodies and in 93% of the patients an elevated level of specific IgG antibodies were detected. All patients showed the positive result in one of the above-mentioned tests. The largest group of the patients (55%) included persons showing the positive result of the skin test and having elevated levels of allergen-specific IgG and IgE antibodies. Thus, in cases of hypersensitivity to house-dust mites the levels of allergen-specific IgG and IgE antibodies in the patients' blood sera should be determined.     

浅部真菌感染和变态反应性皮肤病相关性研究

目的 通过比较合并与未合并浅部真菌感染的变态反应性皮肤病对常用变应原的敏感性,综合从皮肤或指(趾)甲中分离出的菌种情况,评估浅部真菌感染在变态反应性皮肤病的病因学中的作用.方法 受试者包括353例慢性荨麻疹、湿疹及特应性皮炎患者.通过真菌直接镜检法将受试者分为两组.实验组:变态反应性皮肤病合并浅部真菌感染组(n =173);对照组:变态反应性皮肤病无浅部真菌感染组(n=180).对所有实验组及对照组受试者进行9种真菌变应原和9种非真菌变应原皮内试验.实验组患者进一步进行真菌培养以鉴定菌种.结果 慢性荨麻疹患者实验组须发癣菌、新月弯孢霉,特异青霉、烟曲霉变应原阳性率显著高于对照组(P＜0.05),慢性湿疹患者实验组须发癣菌变应原阳性率显著高于对照组(P ＜0.001).慢性湿疹、荨麻疹患者其他真菌变应原及粉尘螨、屋尘螨等非真菌变应原阳性率比较差异均无统计学意义(P＞0.05).134例患者皮肤或指(趾)甲分离鉴定主要为红色毛癣菌(52.86％)、须癣毛癣菌(14.18％)、絮状表皮癣菌(5.22％)、白念珠菌(6.72％),实验组须发癣菌变应原阳性率及皮肤分离皮肤癣菌阳性率比较差异无统计学意义(P＞0.05).结论 实验结果表明,须发癣菌变应原阳性的慢性荨麻疹、湿疹患者往往合并皮肤癣菌感染,皮肤癣菌感染可能在部分慢性荨麻疹、湿疹的病因学中起重要作用.     

The detection of house dust mites in the apartments of children with allergic diseases

The acarological study of house dust in 239 apartments of children with different allergic diseases (bronchial asthma, rhinosinusitis, atopic dermatitis) developing as the result of indoor sensitization has been carried out. The significant difference between the occurrence of house-dust mites in apartments inhabited by healthy and sick children has been established. The occurrence of mites and their number have been found to affect the symptoms of an allergic disease and its exacerbation.     

Immunotherapy in the complex treatment of patients with atopic dermatitis with sensitization to house dust mites

Ninety-nine patients aged 16-52 years with disseminated atopic dermatitis at the remission were examined and treated. The patients were divided into 3 groups according to the method of therapy. Group 1 (28 patients aged 17-52 years, found to be sensitive to Dermatophagoides pteronyssinus and D. farinae) received, in addition to standard treatment, immunotherapy (oral hyposensitization with mite allergens) in combination with ointment containing retinopalmitate and methyluracil. Group 2 (39 patients aged 17-40 years) received standard treatment combined with the administration of placebo. Group 3 (32 patients aged 16-27 years) received only standard therapy. Groups 2 and 3 were used for comparison. The results of treatment were evaluated according to changes in the immune status of the patients and a complex of clinical characteristics. Essential improvement in clinical characteristics and the normalization of immunological parameters were registered in group 1, which proved that immunotherapy was effective and safe.     

Allergy against chironomids (non biting midges) in adult atopic patients

Summary The aim of this investigation was to evaluate the prevalence of atopic sensitization to chironomids (CHI) in patients with asthma and/or rhinitis (A/R), and to study concomitant sensitization to CHI and other allergens. Skin prick tests were performed with 3 different CHI extracts as well as with common inhalant allergens in 600 consecutive patients, 495 of which had A/R. Allergen specific IgE antibodies in the sera against CHI, shell fish and cockroaches were analyzed with Magic Lite.59 (12%) of the patients with A/R had a positive skin test with CHI. Positive skin tests with house dust mites and a storage mite were more common in CHI allergic patients than in other atopic patients. Nasal or conjunctival provocation tests, performed on 23 of the patients with positive skin test with CHI, were clearly positive in 7 cases (30%), questionable in 8 (35%) and negative in 8 cases (35%).Magic Lite, performed on sera from 50 of the patients with positive skin test against CHI, was positive with CHI in 39 cases (78%), with crayfish in 33 (66%), shrimp 20 (40%), cockroach 21 (40%) and with crab in 3 cases (6%).It is concluded that sensitization against CHI is common in patients with A/R. The clinical relevance of the positive test results is, however, unknown. Concomitant sensitization with CHI, crustaceans and cockroach is common.     

House-dust mite sensitivity among rural and urban asthmatics of West Bengal, India: a comparison

House-dust mite allergy is a fairly common problem in West Bengal among individuals sensitive to dust inhalation. House-dust mites belonging to the genusDermatophagoides are abundant in the homes of asthmatic patients residing in urban as well as rural areas of West Bengal. The frequency of positive skin reaction to different dust-related allergens tested was higher (χ²=5.4777, df = 1;P < 0.05) among patients of urban areas compared with that among the patients of rural areas. Urban patients showed more frequent skin reaction towards cockroach allergen, while rural patients are more sensitive to hay-dust allergen and these are very much related to their local environmental conditions. Analysis of radioallergosorbent test (RAST) results against house dust (HD) and mites reveal that 73 and 90% patients of both urban and rural areas responded positively towardsDermatophagoides pteronyssinus (DP) andDermatophagoides farinae (DF) antigens, respectively. The present study indicates no significant difference in house-dust mite sensitivity and mite levels in homes among the rural and urban asthmatics of West Bengal, India as evidenced from the results of analysis of dust samples, allergy skin test and detection of mite-specific IgE antibodies by RAST.     

High Altitude and House-dust Mites

House dust from high mountainous areas of Switzerland contains very few house-dust mites. In contrast to lower-lying regions, only very small quantities of house-dust allergen are found at high altitudes.The cause of this phenomenon seems likely to be the climatic conditions in the high mountains of Europe, where cold air leads to extremely low humidity levels indoors. The soil conditions and a type of construction providing good protection against the penetration of water also contribute to dry conditions in houses. These factors prevent the development of large populations of allergen-producing house-dust mites.The beneficial effect of a stay at high altitudes on patients with atopic asthma is probably due to the low concentrations of house-dust allergen.     

Differential effects of peptidoglycan recognition proteins on experimental atopic and contact dermatitis mediated by Treg and Th17 cells

Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3(-/-) and Pglyrp4(-/-) mice (but not Pglyrp2(-/-) mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3(-/-) and Pglyrp4(-/-) mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3(-/-) and Pglyrp4(-/-) mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3(-/-) mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1(-/-) mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin.     

Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.     

Atopy patch test with Dermatophagoides pteronyssinus (Dp 1) in atopic dermatitis patients

The aim of this study was to evaluate the role of Dermatophagoides pteronyssinus (Dp) in atopic dermatitis patients, using atopy patch test (APT) with Dp (extract 1). Twenty patients (males (m) = 9, females (f) = 11, mean age = 46.0 years, range = 19-78 years) with atopic dermatitis were involved in this study. The control group consisted of seventeen healthy subjects (m = 7, f = 10, mean age = 48.3, range = 24-64 years), with no personal or family history and no signs of atopy. Total IgE, specific IgE and a skin prick test were done for all subjects involved in this study. The atopy patch tests were performed with Dp (extract 1) in: 3,000, 10,000, 20,000 and 30,000 biological units per ml (BU/ml) concentrations using glycerol as medium. The total IgE was significantly higher in atopic dermatitis (AD) patients than in a control group with (p < 0.05). After the tests six of twenty patients (30%) had positive APT results in the last two concentrations (20,000 and 30,000 BU/ml). However, all the results were positive after 48 h (and 72 hours), while no positive results were recorded in the control subjects. According to our study, APT with Dp 1 in 20,000 BU/ml and reading time 48 h and 72 hours is to be recommended. The results suggest that APT may detect the trigger factor (Dp) in AD patients.     

Two-dimensional electrophoresis of Malassezia allergens for atopic dermatitis and isolation of Mal f 4 homologs with mitochondrial malate dehydrogenase.

The yeast Malassezia furfur is a natural inhabitant of the human skin microflora that induces an allergic reaction in atopic dermatitis. To identify allergens of M. furfur, we separated a crude preparation of M. furfur antigens as discrete spots by 2-D PAGE and detected IgE-binding proteins using sera of atopic dermatitis patients. We identified the known allergens, Mal f 2 and Mal f 3, and determined N-terminal amino acid sequences of six new IgE-binding proteins including Mal f 4. The cDNA and genomic DNA encoding Mal f 4 were cloned and sequenced. The gene was mitochondrial malate dehydrogenase and encoded Mal f 4 composed of 315 amino acids and a signal sequence of 27 amino acids. We purified Mal f 4, which had a molecular mass of 35 kDa from a membrane fraction of a lysate of cultured cells. Thirty of 36 M. furfur-allergic atopic dermatitis patients (83.3%) had elevated serum levels of IgE to purified Mal f 4, indicating that Mal f 4 is a major allergen. There was a significant correlation of the Phadebas RAST unit values of Mal f 4 and the crude antigen, but not between Mal f 4 and the known allergen Mal f 2.     

ATOPIC DERMATITIS DUE TO SENSITIVITY TO POLLEN

Observation of 100 patients with atopic dermatitis due to hypersensitivity to pollen over a period of 12 years emphasized certain important diagnostic and therapeutic features. The incidence was higher in females than in males and higher in middle and old age than in the earlier years.Pollen dermatitis may be the sole or major manifestation of allergy; 43 patients gave no history of other allergic symptoms. It may involve any or all areas of the body. The site or the distribution of lesions or the nature of the lesions gave no clue as to the diagnosis of pollen sensitivity.The character of the eruption varied widely from patient to patient and in given patients from week to week at times.Atopic dermatitis due to pollen sensitivity may be purely seasonal, perennial with seasonal exacerbations or perennial without seasonal variation.Reactions to skin testing with pollens suspected as allergens may be positive, equivocal or negative. In 58 patients there were positive correlative skin reactions to pollens.The diagnosis of atopic dermatitis due to pollen sensitivity, and the composition of the desensitizing antigen or antigens, must be based primarily on the clinical history and the area of residence.Most patients could tolerate only very weak dilutions at the beginning of desensitization therapy. Strong dilutions caused exacerbation of the dermatitis.Good or excellent results were obtained with perennial pollen desensitization therapy administered over long periods. In 13 patients good results took four to eight years of desensitization therapy. Fifty required less than two years. Tolerance of the patient for a given dose of antigen should determine the maximum dilution used in therapy.     

Inhibitory effects of polysaccharide-rich extract of Phragmites rhizoma on atopic dermatitis-like skin lesions in NC/Nga mice

AimsPhragmites rhizoma was reported to have anti-oxidative and free radical scavenging activity. It also has been traditionally used to suppress inflammation. In the present study, we aimed to evaluate the topical effects of the polysaccharide-rich extract of P. rhizoma (PEP) on atopic dermatitis.Main methodsWe induced AD-like skin lesions by an extract of the house-dust mite Dermatophagoides farinae (Dfb) in NC/Nga mice, and then performed macroscopic analysis, immunohistochemical staining and measurement of total serum IgE and cytokine production by ELISA.Key findingsTopically applied PEP suppressed dermatitis with a decrease in dermatitis score and scratch number. The histological manifestations of atopic skin lesions including thickened epidermis and increased numbers of mast cells, polymorphonuclear leukocytes and nerve fibers were significantly attenuated. The activation of IgE and the levels of cytokines such as IFN-γ IL-4 and IL-10 were also decreased.SignificanceOur results indicated that PEP might have an inhibitory effect on atopic dermatitis-like lesion and be a promising natural resource in the treatment of atopic dermatitis.     

Effectiveness of benzyl benzoate in elimination of house dust mites

The effect of elimination treatment with benzyl benzoate was examined in 30 adults with asthma caused by sensitivity to house dust mites. The patients were randomised into a control and an active group, who treated their mattresses with benzyl benzoate (Acarosan^®). The study lasted 12 months and the effect of the treatment was monitored by monthly dust sampling, analyzed for major allergens fromDermatophagoides pteronyssinus andfarinae by the ELISA method and for guanine by the Acarex^® method. The clinical effect was assessed by measuring lung function, daily peak flows, symptoms and medicine consumption as well as skin prick tests, and specific IgE to mite allergens. For both groups, a significant decrease was observed in house dust mite allergens, but there was no significant difference between the groups. No considerable differences were observed in clinical parameters within or between the groups. A good correlation was observed between ELISA and Acarex^®. but the latter showed a major variation in the different classes. In conclusion. treatment of mattresses with benzyl benzoate had no effect in a group of patients with asthma due to house dust mite allergy. Regular vacuum cleaning of the bed may reduce house dust mite allergen exposure.     

Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity

Skin inflammation in atopic dermatitis starts with Th2 and IgE-mediated responses against exogenous allergens and, for unknown reasons, resembles features of a Th1-driven reaction in the chronic stages. We report the characterization of a human protein, Hom s 4, recognized by IgE autoantibodies from atopic dermatitis patients. The complete Hom s 4 cDNA codes for a 54-kDa basic protein containing two typical calcium-binding domains separated by an unusually long alpha-helical domain. Therefore, Hom s 4 and homologous proteins found by sequence comparison in mice, fruit flies, and nematodes constitute a novel subfamily of calcium-binding proteins. Using Hom s 4-specific Abs, it is demonstrated that the protein is strongly expressed within epidermal keratinocytes and dermal endothelial cells. Purified Hom s 4 showed IgE cross-reactivity with exogenous calcium-binding allergens from plants and fish but, in contrast to the exogenous allergens, induced only weak histamine release from patient basophils. However, the analysis of Hom s 4-specific cytokine and humoral immune responses indicated that Hom s 4 strongly induces Th1 responses which are accompanied by the release of IFN-gamma, a cytokine implicated in epithelial cell damage. Hom s 4-induced IFN-gamma production was found in normal individuals, in patients with chronic inflammatory skin diseases and in Th2-prone atopic persons, suggesting that Hom s 4 represents a protein with an intrinsic property to induce Th1-mediated autoreactivity. It may thus contribute to chronic skin inflammation in atopic as well as in nonatopic persons.     

Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis

In a systematic analysis of global gene-expression patterns, we found that SOCS3 messenger RNA was significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls, and immunohistochemical analysis confirmed a similar elevation of SOCS3 protein. Furthermore, we found a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene in two independent groups of patients (P<.02 and P<.03). These results strongly suggest that SOCS3, located in a chromosomal region previously linked to the disease (17q25), is a susceptibility gene for atopic dermatitis.     

CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell-derived chemokine, is regulated by staphylococcal products and allergen exposure

Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence. Exposure to allergens or bacterial superantigens triggers T and dendritic cell (DC) recruitment and induces atopic skin inflammation. In this study, we report that among all known chemokines CCL18/DC-CK1/PARC represents the most highly expressed ligand in atopic dermatitis. Moreover, CCL18 expression is associated with an atopic dermatitis phenotype when compared with other chronic inflammatory skin diseases. DCs either dispersed within the dermis or clustering at sites showing perivascular infiltrates are abundant sources of CCL18. In vitro, microbial products including LPS, peptidoglycan, and mannan, as well as the T cell-derived activation signal CD40L, induced CCL18 in monocytes. In contrast to monocytes, monocyte-derived, interstitial-type, and Langerhans-type DCs showed a constitutive and abundant expression of CCL18. In comparison to Langerhans cells, interstitial-type DCs produced higher constitutive levels of CCL18. In vivo, topical exposure to the relevant allergen or the superantigen staphylococcal enterotoxin B, resulted in a significant induction of CCL18 in atopic dermatitis patients. Furthermore, in nonatopic NiSO4-sensitized individuals, only relevant allergen but not irritant exposure resulted in the induction of CCL18. Taken together, findings of the present study demonstrate that CCL18 is associated with an atopy/allergy skin phenotype, and is expressed at the interface between the environment and the host by cells constantly screening foreign Ags. Its regulation by allergen exposure and microbial products suggests an important role for CCL18 in the initiation and amplification of atopic skin inflammation.     

The antibacterial activity of plaunotol against Staphylococcus aureus isolated from the skin of patients with atopic dermatitis.

Plaunotol was tested for possible antibacterial activity against twenty strains of methicillin-resistant Staphylococcus aureus (MRSA) and fourteen strains of methicillin-sensitive S. aureus (MSSA) which had been isolated from the skin of patients with atopic dermatitis under growth-promoting conditions. Plaunotol was effective against all strains tested. The dose of plaunotol for 50% inhibition of growth (ID50) ranged from 2.5 to 16 micrograms/ml for strains of MRSA and from 2.5 to 7.0 micrograms/ml for those of MSSA. These results suggest that plaunotol may be useful in the prevention of infection by MRSA and in skin care for patients with atopic dermatitis.