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Modulation of CD3-dependent lymphocyte proliferation by extracellular matrix proteins in atopic dermatitis.

Patients with atopic dermatitis were found to have an about 7-fold increased spontaneous proliferative response of peripheral blood lymphocytes and an about 4-fold elevation of CD3-dependent lymphocyte transformation as compared to normal controls. The CD3-dependent lymphocyte response in patients with severe atopic dermatitis lesions was increased to a lower degree than in those with mild skin lesions. Despite a highly increased CD3-dependent lymphocyte response, the extracellular matrix proteins could induce further co-stimulation of lymphocytes in patients with atopic dermatitis, similar to that in normal controls. However, co-activation by type IV collagen was markedly increased in patients with severe lesions, whereas co-stimulations by both type I collagen and fibronectin were decreased in patients with mild lesions. This finding reflects presumably the changes in lymphocyte subpopulations and their activities related to the recirculation of these cells through the active skin lesions and to the contact of T cells with extracellular matrix proteins. The percentage of CD26-positive lymphocytes was also significantly (p < 0.05) increased in patients with severe atopic dermatitis. These data indicate that helper T cells are excessively activated in atopic dermatitis and that the function of beta-1-integrin receptors underlying the extracellular matrix protein-mediated co-activation of CD3-dependent lymphocyte responses is modified by disease severity.

Adolescent↗

Allergic contact dermatitis in patients with atopic dermatitis: A clinical study.

BACKGROUND: Atopic dermatitis (AD) is a chronically relapsing dermatitis with no known cure. Due to the chronic nature of the condition, frequent and long term topical therapy is used. This may lead to sensitization, resulting in allergic contact dermatitis (ACD). AIMS: The aim of the study was to observe the frequency of ACD in atopic patients in this part of the country using Indian standard battery. METHODS: A total number of 30 cases of AD were taken for the study. Diagnosis of AD cases was based on the criteria of Hannifin and Rajka (1980). All the selected cases of AD had mild to moderate grade of severity. All these cases were treated and patch tested during the remission period. The duration of the study was 12 months. RESULTS: Out of the 30 AD cases, 7 cases showed positive ACD with patch test allergens. CONCLUSION: This study shows that ACD is not uncommon amongst atopic individuals.

Adolescent↗

[Comparative treatment between thalidomide and transfer factor in severe atopic dermatitis].

AIMS: The atopic dermatitis is an chronic inflammatory illness of the skin. It exists an interrelation complex of factors gene, environmental, and psychological that contribute to the development and severity of the illness. The immunol aberrations significant is the answer increased of IgE specific antibodies toward antigens common, the liberation is increased of immunol mediators by the basophils and mast cells, eosinophils peripheral and local, besides enlarges the biphasic activity Th1/Th2 with liberation of cytokines (IL-4, IL-5, IL-13), GM-C5F, and decrease of IFN-gamma by the cells Th1. Leung to report a knowledge upon the bases immunopathologies of it atopic dermatitis has immunopathologies clinical important for the diagnosis and processing. Alternatives multiples of processing by the same complexity of the illness exist. OBJECTIVE: To compare the security and the clinical efficacy of the thalidomide and the factor of transfer in the atopic dermatitis severe. MATERIAL AND METHOD: Were studied patient with diagnosis of atopic dermatitis severe in agreement with the criterions of Hanifin and Rajka that they entered to the service of Allergy and Immunology Clinical of the Hospital Regional Lic. Adolfo López Mateos (public hospital). They were included 19 patient (women 12 and men 7, with age average 30 +/- 4 years). They were distributed in two groups. The first group of 5 patient administration thalidomide 200 mg/d during six months. The second group am administered the factor of transfer a total of 15 units by road oral during six months. Studies of laboratory for appraisal were requested immunology and metabolic pretreatment and pretreatment. RESULTS: In the group A dealt with thalidomide 5 patient and the group B dealt with FT, both presented a statistically significant decrease, as for the extension of the wounds (p < 0.01), and 1 am observed greater reduction in the intensity of the symptoms, the SCORAD total (p < 0.001 and p < 0.001 respectively) with statistical difference among them. None presented alterations immunologies and metabolic secondary to the use of the two drugs and not there was the need to suspend the processing. During the period of study, the patient were maintained controlled to the allergic rhinitis and the asthma. DISCUSSION: In the atopic dermatitis by its secondary clinical complexity to the multifactors etiologic, the alternatives of processing utilized in the present study are an option the security and efficacy, I am observed better clinical.

Adult↗

The genetics of psoriasis, psoriatic arthritis and atopic dermatitis.

Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin associated with various immunologic abnormalities. Approximately 30% of psoriasis patients also have joint involvement, indicative of psoriatic arthritis. Genes and environment play a key role in the pathogenesis of these diseases. Genome-wide linkage scans have identified multiple loci linked to each disease and revealed overlap with psoriasis and atopic dermatitis susceptibility loci on chromosomes 1q21, 3q21, 17q25 and 20p12. The genes from these loci have not yet all been identified, or systematically tested for a role in psoriasis and atopic dermatitis; however, these locations suggest that some susceptibility factors lie within genes or gene families with common effects upon epithelial immunity. A strong HLA association is described for psoriasis, but not for atopic dermatitis. Knowledge of the genetic factors leading to these diseases will lead to an understanding of their variable age at onset, their waxing and waning and the variability of body surface environment. The effect of environmental triggers may also be understood once the altered pathways are elucidated. Genes implicated so far in atopic dermatitis are SPINK5, FcepsilonRI-beta and PHF11. Genes implicated in psoriasis so far are HLA-C, SLC9A3R1, NAT9, RAPTOR and SLC12A8. Genetic modifiers such as CARD15 may predispose to psoriatic arthritis.

Arthritis, Psoriatic↗

927T>C polymorphism of the cysteinyl-leukotriene type-1 receptor (CYSLTR1) gene in children with asthma and atopic dermatitis.

Asthma and atopic dermatitis share several common features and Cysteinyl-leukotrienes are mediators that participate in the pathogenesis of both diseases. Recently, a new polymorphism (927T>C) has been identified in cysteinyl-leukotriene type-1 receptor (CYSLTR1) gene. This gene is found on the X chromosome. The aim of this study was to analyze this SNP in a population of children with asthma and atopic dermatitis. In this study, 166 individuals, 79 adult controls (CTR) and 87 children with asthma (AA) were included. Forty-one patients with asthma presented atopic dermatitis (AA-AD). Adults were chosen as controls to confirm lack of development of asthma and allergy during childhood. Standardized history, physical examination, skin prick tests, and lung function measurements were performed in all patients. The 927T>C CYSLTR1 SNP was analyzed by direct sequencing after PCR amplification. In males (53 individuals), the C allele was significantly more common among AA-AD patients (47%) than in CTR (8%) (Fisher's p < 0.005; Monte Carlo p < 0.008; OR:9.78; 95%CI: 1.73-55.30). When comparing AA-AD vs. AA-NAD (patients with asthma but not atopic dermatitis), significant differences were observed, (47% vs. 15%, Fisher's p = 0.014; Monte Carlo p = 0.022; OR: 4.97; 95%CI: 1.29-19.13). No differences in allele distribution were observed between these disease sub-groups in females. The 927T>C is a silent SNP; however, it could affect transcription or translation or may be linked to an unidentified, functional polymorphism and thus may pre-dispose male children to asthma and atopic dermatitis in our population. Further studies are needed to confirm these findings.

Adolescent↗

Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis.

Treatment of atopic dermatitis with essential fatty acids remains controversial. A double-blind, placebo-controlled, parallel-group study was done to investigate the response of patients with atopic dermatitis to essential fatty acid supplements. Patients with atopic dermatitis were randomised to receive evening primrose oil, evening primrose oil and fish oil, or placebo for 16 weeks. Disease activity was monitored by clinical severity scores recorded by the investigator, topical steroid requirement, and symptom scores recorded by subjects. Of 123 subjects recruited, 102 completed the treatment period. No improvement with active treatment was demonstrated. Our study, which avoided the methodological and analytical problems of previous studies, found no effect of essential fatty acid supplementation in atopic dermatitis.

Adult↗

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs.

Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.

Animals↗

[Psychological, immunological, and endocrinological implications of atopic dermatitis].

BACKGROUND: The atopic dermatitis is a chronic disease with immunological alterations, neuro-immune-endocrine implications and repercussions in the psyche. OBJECTIVE: To determine the effectiveness of the use of psychological support in the treatment of atopic dermatitis. MATERIAL AND METHODS: This study included 20 patients (from 15 to 50 years old) with moderated and severe atopic dermatitis based on the Hanifin and Rafka modified criteria. They were classified in three groups of treatment: A) 10 patients with transfer factor and psychological support, B) 10 with transference factor without psychological support, C) 10 healthy individuals as a control group. At the beginning and ending of the analysis the degree of severity of the illness was determined using the SCORAD scale. RESULTS: There was a more statistically significant clinical improvement on group A than in group B, besides a decrease in anxiety and depression, at a laboratory level including hormonal behavior, without meaningful changes. CONCLUSIONS: It was demonstrated that the treatment with immune-modulator and psychological support on the moderated and severe atopic dermatitis improves the clinical and immunological evolution of this illness.

Adjuvants, Immunologic↗

Role of staphylococcal enterotoxins in pathogenesis of atopic dermatitis: growth and expression of T cell receptor V beta of peripheral blood mononuclear cells stimulated by enterotoxins A and B.

In order to investigate the role of staphylococcal enterotoxins in the pathogenesis of dermatitis in atopic patients, the growth and expression of T cell receptor V beta in peripheral blood mononuclear cells (PBMCs) from atopic dermatitis patients induced by stimulation with staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB) were examined. Lymphocyte stimulation tests (LST) using SEA or SEB were performed in atopic dermatitis (AD) patients (n = 10) and normal controls (n = 5). PBMCs from AD patients displayed significantly stronger responses to SEA or SEB than those from the controls. To ascertain further whether SEA acts as a superantigen in atopic dermatitis, the expression of 22 genes in the variable region of the beta chain (V beta) of T cell receptors (TcR) was examined before and after stimulation with SEA by a reverse transcriptase-polymerase chain reaction (RT-PCR). Before stimulation, only weak expression of V beta was observed, and the expression of the various V beta segments was uniform in the normal controls (n = 3). In the AD patients (n = 3), the expression of V beta was enhanced, but was not uniform in 2 out of 3 patients and the pattern of expression was characteristic in each individual. This suggests that V beta expression varies in individual AD patients and displays restricted heterogeneity, reflecting the diversity of the etiology of the disease. After culture of the SEA-stimulated cells, no difference was observed in the expression of TcR V beta segments in the 3 normal controls as compared with that prior to stimulation, but particular V beta segments were intensely expressed in 3 AD patients, displaying distinct patterns (case I: V beta 9, V beta 10, V beta 18; case 2: V beta 6.1-3; case 3: V beta 6.1-3, V beta 18). Many of these V beta segments corresponded with those known to be induced by SEA. These results suggest oligoclonal proliferation of T cells in the peripheral blood of AD patients and high responsiveness in each clone, and since the expression of V beta segment after SEA stimulation was restricted, the actions of staphylococcal enterotoxins as superantigens were suggested.

Adolescent↗

Antibacterial effect of beta-thujaplicin on staphylococci isolated from atopic dermatitis: relationship between changes in the number of viable bacterial cells and clinical improvement in an eczematous lesion of atopic dermatitis.

Beta-thujaplicin (hinokitiol) is a tropolone-related compound purified from the wood of Chamaecyparis obtusa, SIEB: et Zucc. and Thuja plicata D. Don. All Staphylococcus aureus isolates were inhibited by beta-thujaplicin with MICs of 1.56-3.13 mg/L. However, a paradoxical zone phenomenon occurred, with each isolate producing regrowth at higher beta-thujaplicin concentrations. Other antimicrobial agents showed a wide range of MICs. The combination of beta-thujaplicin and zinc oxide inhibited the paradoxical zone phenomenon, and enhanced killing activity against clinically isolated staphylococci. Large numbers of viable bacterial cells, especially S. aureus cells, were detected in the skin surface of atopic dermatitis, in comparison with those in healthy volunteers. The number of cells increased as the severity of the skin condition worsened. Topical application of beta-thujaplicin resulted in a reduction in the number of bacterial cells on the skin surface, and an improvement in skin condition after treatment. The results of this study suggest that the degree of reduction in the number of viable bacterial cells in an eczematous lesion of atopic dermatitis is related to the degree of improvement in skin condition.

Adolescent↗

Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are not associated with susceptibility to atopic dermatitis, but two of them in the promoter region are associated with serum IgE levels in patients with atopic dermatitis.

Eotaxin is believed to play an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD on chromosome 17 were reported. Recently we have identified single nucleotide polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes of AD, we investigated the genotype frequencies at each SNP of the gene in AD patients and in controls. We examined 140 Japanese AD patients and 140 healthy Japanese individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was observed in allele or genotype frequencies of any SNP between AD patients and controls. Serum immunoglobulin E (IgE) levels were significantly lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in AD patients. Eotaxin gene SNPs in the promoter and exon regions are not associated with susceptibility to AD, but two of them in the promoter region are associated with phenotype of AD.

Adolescent↗

Chemical mediators in atopic dermatitis: involvement of leukotriene B4 released by a type I allergic reaction in the pathogenesis of atopic dermatitis.

BACKGROUND: The mediators produced from a type I allergic reaction have not yet been able to explain the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to elucidate the involvement of leukotriene (LT) B4 produced from a type I allergic reaction in the pathogenesis of AD. METHOD: The release of LTB4 was measured both in vitro, in passively sensitized and antigen-challenged human skin slices, as well as in vivo, in skin chambers on patients with AD. RESULTS: LTB4 was released from in vitro human skin by stimulation of the antigen (54.9 +/- 14.6 pg/g wet weight of skin by antigen challenge and 28.0 +/- 11.1 pg/g in control skin, P <.002). Antigen-specific release of LTB4 and histamine was also observed in vivo in nonlesional skin from the patients with AD by using the skin chamber technique. CONCLUSION: LTB4 release during type I allergic reaction in human skin has been determined in vitro. The released LTB4 possibly contributes to cellular response at the acute inflammatory lesion of AD.

Adolescent↗

Characterization by phenotype of families with atopic dermatitis.

The aetiology of atopic dermatitis is unknown, but is probably multifactorial, with interactions between several genetic and environmental factors. Twin studies indicate a strong genetic factor, but the susceptibility genes are unknown. This paper, describing the phenotypes of family material, forms part of a large genetic study seeking to identify susceptibility genes for atopic dermatitis by linkage analysis. We selected families with at least 2 siblings affected with atopic dermatitis (1,097 affected siblings who together form 650 affected sib pairs and 49 affected half-sib pairs). We established a phenotype database of information about the affected siblings and their relatives, in total 5,830 individuals. All siblings were diagnosed with atopic dermatitis and participated in a standardized interview covering aspects of atopy and atopic dermatitis. Of the affected siblings, 72% suffered or had suffered from asthma and/or allergic rhinoconjunctivitis and 74% had raised total and/or allergen-specific IgE serum levels. Seventeen percent of the siblings had been hospitalized for atopic dermatitis. Sixty-nine percent had 1 or both parents with atopic dermatitis. Among siblings with 1 parent with atopic dermatitis, 37% had a father with atopic dermatitis and 63% had a mother with atopic dermatitis, indicating maternal preponderance. Analysis of the occurrence of atopic dermatitis in relation to the birth order in the sibship shows an increased risk of atopic dermatitis in persons born early in a sibship. Although the families were selected for genetic sib-pair linkage analysis, we believe that this material is representative of atopic dermatitis families managed at hospitals in Stockholm.

Adolescent↗

Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?

Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.

Adolescent↗