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PubMed1995

Upregulation of IgE synthesis by staphylococcal toxic shock syndrome toxin-1 in peripheral blood mononuclear cells from patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease associated with increased IgE synthesis and colonization with Staphylococcus aureus secreting exotoxins, such as Toxic Shock Syndrome Toxin-1 (TSST-1). OBJECTIVES: In this study, we were interested in determining the in vitro effects of TSST-1 on IgE synthesis in peripheral blood mononuclear cells from patients with AD. METHODS: We stimulated peripheral blood mononuclear cells (PBMC) from AD patients with a wide range of TSST-1 concentrations and measured IgE synthesis by enzyme-linked immunosorbent assay (ELISA) after 14 days. RESULTS: We show herein that TSST-1 produced antagonistic effects on IgE synthesis by PBMC from AD patients, depending on the concentration used: IgE synthesis was inhibited at 1000 pg/mL (P < 0.05) and enhanced at 0.01 pg/mL (P < 0.01) of toxin. TSST-1 was found to induce the production of much higher amounts of interferon-gamma (IFN gamma) at 1000 pg/mL than at 0.01 pg/mL of toxin (P = 0.0001). More importantly, immunoglobulin E (IgE) synthesis was enhanced by TSST-1 at 1 pg/mL in the presence of antibodies blocking IFN gamma activity. The other immunoglobulin (Ig) isotypes were also increased after TSST-1 stimulation suggesting that the enhanced IgE synthesis was secondary to a polyclonal B cell activation rather than an isotype switch. TSST-1-stimulated IgE synthesis was T cell-dependent because purified tonsil B cells were only able to synthesize increased amounts of IgE when small numbers of T cells were added to the cultures. Anti-HLA-DR and anti-LFA-1 monoclonal antibodies (MoAb) inhibited TSST-1-enhanced IgE synthesis, suggesting that the bridging of the T cell receptor (TCR) and major histocompatibility complex (MHC) class II on B cells was necessary for activation of B cell differentiation. CONCLUSION: These data indicate that staphylococcal superantigens are able, at concentrations inducing low amounts of IFN gamma, to stimulate IgE synthesis by PBMC from AD patients, and suggest that staphylococcal toxins may contribute to elevated IgE synthesis in AD.

Adjuvants, Immunologic↗
PubMed2006

No association of cytokine gene polymorphisms in Chinese patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with the activation of T-helper 2 cells. Recent studies have shown that polymorphisms in the genes for interleukin (IL)-4, the IL-4 receptor, IL-13, and signal transducer and activator 6 (STAT6) may contribute to susceptibility of AD. To date, no cytokine gene polymorphism study has been conducted on Chinese patients with AD. AIMS: To determine whether genetic polymorphisms of the cytokine genes might influence the development of AD. METHODS: DNA samples were obtained from 94 patients and 186 control subjects. Using direct sequencing and microsatellite genotyping, we examined 22 polymorphisms in eight cytokine genes including the genes for IL-4, -10, -12B and -13, the IL-4 receptor, tumour necrosis factor (TNF)-alpha, STAT6, and interferon (IFN)-gamma. RESULTS: No significantly different allelic and genotypic distributions of the cytokine gene polymorphisms could be found between patients and controls. Moreover, no association was observed with disease onset, gender, the presence of elevated serum total IgE level or blood eosinophilia. CONCLUSION: Our study suggests that the analysed genetic polymorphisms of cytokine genes do not appear to be associated with AD susceptibility in our Chinese population.

Adolescent↗
PubMed2006

Mycophenolate mofetil therapy for moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD. AIM: To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic. METHODS: A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects. RESULTS: Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus. CONCLUSION: MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.

Adult↗
PubMed1999

Is atopic dermatitis predictable?

Atopic dermatitis (AD) is a common skin disease which affects 10 to 20% of the population, usually with onset during infancy. The frequency of AD appears to have increased over the past three decades. Attempts to identify parameters predictive of the development of AD have been made by many investigators during the last decades. Although genetic factors remain unmodifiable, avoidance of relevant trigger factors could modify the development of AD. This paper reviews and discusses findings of the last several years and outlines recent advances in genetic studies of AD. In spite of decades of intensive research and newly developed technology, the parental history of AD appears to be the most valuable predictive parameter. However, the predictive capacity is not sufficient to recommend it as screening instrument. At this time, a perinatal screening with the objective of primary prevention of AD does not seem feasible.

Cytokines↗
PubMed2004

Semiquantitative scoring in children under treatment for atopic dermatitis.

BACKGROUND: Atopic dermatitis is the most frequently seen childhood allergic disease in outpatient clinics. Improvement, exacerbation, and response to treatment are typically assessed subjectively and occasionally inaccurately. METHODS: The authors developed two forms for scoring of dermal manifestations and used them to assess 56 children. The correlation between two pediatricians' scores and correspondence to established categories (mild, moderate, and severe) were determined. RESULT: The two physicians' scores for the children correlated well for both forms of scoring. Correspondence of scores as 'mild' and 'moderate' categories were significant (few children participating were 'severe'). CONCLUSION: Use of well-constructed scoring forms should improve clinical assessment of patient course and treatment response.

Child↗
PubMed2004

Impaired interferon-gamma production in a subset population of severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic chronic eczema. The immunopathogenesis of this condition is still not well understood. We assessed the transcription and production of IFN-gamma, the Th1 cytokine, and the Th2 cytokine IL-5 in peripheral blood mononuclear cells (PBMCs) from patients with severe AD. METHODS: The subjects included 17 severe (serum IgE: 5,000-92,000 U/ml, median: 20,000 U/ml), 4 mild AD (IgE: 2-520 U/ml) and 8 nonatopic controls (IgE: <100 U/ml). The severe AD patients were classified into two groups according to the response to standard treatment with topical glucocorticoids. Individuals were classified as poorly responsive (AD-P) if the clinical score decreased less than one third after 2 weeks of hospital treatment and as responsive (AD-R) if the score decreased more than one third. PBMCs isolated from the subjects were stimulated with PHA and PMA. RESULTS: The expression of IFN-gamma in PBMCs in the AD-P group was much lower than that observed in the other groups at both mRNA and protein levels. There were no significant differences in the levels of IL-5 both in mRNA and protein levels between the groups. There were no significant differences in STAT4 DNA-binding activity following PHA/IL-2/IL-12 stimulation between AD-P and controls. CONCLUSIONS: These results suggest that the decreased INF-gamma production may account for the abnormal immunopathogenesis of severe, intractable AD.

Adolescent↗
PubMed2006

Association of beta-defensin 1 single nucleotide polymorphisms with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic multifactorial allergic disease with unclear etiology. The antimicrobial human beta-defensin 1 is chemotactic for dendritic cells, which are important regulators of allergic immune responses. In an attempt to identify useful markers that could predict susceptibility to AD, we investigated single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) with potential functional consequences. METHODS: Four SNPs of the DEFB1 gene were genotyped either by real-time polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphisms in 59 patients with AD and 151 controls from the Mexican population. Correlation analyses were carried out between genetic, environmental and clinical variables in AD patients. RESULTS: The genotypes associated with susceptibility to AD and no other allergy were 692 GG (OR = 3.21, 95% CI 1.37-7.34) and 1654 AA (OR = 17.37, 95% CI 1.62-860.83). The allele 668 C is a risk factor for AD (OR = 2.23, 95% CI 1.22-4.01) and the allele A in site 1836 correlates with earlier age at onset (Spearman's rho = 0.232; p = 0.03). The prolonged duration of breastfeeding correlates with earlier age at onset as well as with the severity of AD. CONCLUSIONS: The DEFB1 gene is probably involved in the incidence and development of AD, but additional functional studies will be necessary to understand the biological role of these SNPs.

Adolescent↗
PubMed2001

Tacrolimus ointment for the treatment of atopic dermatitis.

(1) Atopic dermatitis (AD) is a chronic dermatological condition characterized by pruritus (itchiness) and rash. Topical corticosteroids are the mainstay of pharmacotherapy. (2) Tacrolimus ointment is a new topical anti-inflammatory agent available in Canada through the Special Access Program. (3) It is approved as a second line agent for short or long term intermittent treatment of moderate to severe AD. (4) Clinical trials suggest it is both effective and safe, but comparative studies with corticosteroids and long-term information are limited.

Canada↗
PubMed2006

Efficacy and safety of tacrolimus ointment in pediatric Patients with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an immunological skin disease. It is common in pediatric populations and often requires topical steroid treatment. Moderate to severe AD may not respond to topical steroids. They often require systemic steroids, which may result in growth retardation. Protopic, a non-steroid, tacrolimus based ointment which is a calcinurin inhibitor has been proved to be effective in caucacian with AD. OBJECTIVE: To evaluate safety and efficacy of 0.03% tacrolimus ointment (Protopic&) in moderate to severe AD in pediatric patients age 2-12 years. MATERIAL AND METHOD: This was a one month multicenter open-label clinical trial using tacrolimus ointment twice daily in 61 subjects with moderate to severe AD from September to December 2004. Efficacy assessments were measured by Physician's Global Evaluation of Clinical Response (PhGECR), Eczema area and Severity Index (EASI), Patient's Global Evaluation of Clinical Response (PaGECR), and Quality of Life (QOL). Safety assessment was measured by incidence rate of adverse events. RESULTS: Fifty-eight patients completed the studies. Twenty-two patients were male; thirty-nine patients were female. Twenty-nine patients had moderate AD. Thirty-two patients had severe AD. Three cases had discontinued treatment at the third week due to increase in severity. Over all PhGECR were significantly increased, 94% showed moderate improvement in PhGECR at week 4 or end of treatment (EOT)and 83% had better improvement in PaGECR at EOT Within 7 days, tacrolimus demonstrated rapid onset in reduction of EASI score and itch in patients. Mean QOL were significantly decreased at the end of the present study. Incidence of adverse events included application site burning (21%), itching (17%), pruritus (9%), infections(3%), and erythema and folliculitis (2%). Burning sensation, erythema, pruritus and itching were resolved after the first week. CONCLUSION: Topical tacrolimus ointment is effective and safe in moderate to severe AD. It significantly improved PhGECR, EASI, PaGECR, and QOL in pediatric patients after the first week of treatment and continued through the end of the study. The major adverse events were burning, itching, and pruritus, which were resolved within the first week of therapy.

Administration, Topical↗
PubMed1992

Fc epsilon receptor II/CD23+ lymphocytes in atopic dermatitis. III. Aberrant control in the in vitro expression of Fc epsilon RII/CD23 on peripheral blood T cells in atopic dermatitis.

In vitro Fc epsilon RII expression was examined in patients with atopic dermatitis, those with non-atopic eczematous dermatitis and normal individuals following stimulation of peripheral blood cells with recombinant IL-4 (rIL-4), phytohaemagglutinin (PHA), or PHA plus rIL-2. At various days cells were stained with MoAbs to human lymphocyte Fc epsilon RII and to lymphoid cell-surface antigens and analysed by flow cytometry. rIL-4, but not rIL-2, specifically induced Fc epsilon RII on T cells as well as B cells in atopic dermatitis, eczematous dermatitis and normal individual groups. Both atopics and non-atopics generated comparable proportions of Fc epsilon RII+ T cells (T epsilon cells), whereas the frequency of B cells bearing Fc epsilon RII(B epsilon cells) was significantly higher in patients with extensive atopic dermatitis than in those with mild atopic dermatitis and other subjects. Comparable levels of T epsilon cells were detected in both atopic and non-atopic donors following stimulation of peripheral blood cells with PHA or pre-activation of the cells with PHA plus subsequent incubation with rIL-2. Whereas both CD8+ and CD4+ subsets were present in T epsilon cell populations induced specifically by rIL-4, PHA and PHA plus rIL-2, patients with atopic dermatitis had a greater tendency for Fc epsilon RII expression on CD8+ T cells compared with patients with eczematous dermatitis and normal individuals. Recombinant interferon-gamma (rIFN-gamma), but not rIFN-alpha or prostaglandin E2 (PGE2), suppressed the generation of T epsilon cells by rIL-4 in atopics and non-atopics to the same degree. These results suggest the aberrant control of Fc epsilon RII expression on T cells, especially those bearing CD8, in atopic dermatitis.

Adolescent↗
PubMed1990

House dust mites and atopic dermatitis. A case-control study on the significance of house dust mites as etiologic allergens in atopic dermatitis.

The occurrence of house dust mites was measured in homes of 24 patients with atopic dermatitis, 30 patients with mite-sensitive asthma and 32 patients with asthma not related to house dust mites. Patients with mite-positive asthma and patients with atopic dermatitis had significantly higher exposure to house dust mites compared with patients with mite-negative asthma. For atopic dermatitis the higher exposure to house dust mites corresponded to a relative risk of 4.7 and a clear dose-response relationship was demonstrated between exposure and risk of disease in the subgroups of patients with atopic dermatitis. The present epidemiologic results support the idea that house dust mites may be an etiologic factor in a proportion of adult patients with atopic dermatitis.

Allergens↗
PubMed1993

Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis.

BACKGROUND: Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. AIMS: To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index. METHODS: Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within- and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two-way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. RESULTS: For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a 'severity' component; the second one, accounting for 18% of variance, was interpreted as a 'profile' component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution x intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. CONCLUSION: The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials.

Adolescent↗
PubMedDate not supplied

Comparison of severity scoring of atopic dermatitis values and serum levels of eosinophil cationic protein and mast cell tryptase for routine evaluation of atopic dermatitis.

In this study the routine use of different parameters for evaluation of the overall therapeutic outcome in atopic dermatitis was investigated. The disease activity of 117 randomly selected hospitalized patients suffering from atopic dermatitis was routinely assessed using the Severity Scoring of Atopic Dermatitis (SCORAD) index on admission and at discharge. Serum levels of eosinophil cationic protein and mast cell tryptase were determined in parallel both on admission and at discharge. After a mean treatment period of 24+/-12 days a decrease in the SCORAD index from 47.6+/-19.5 to 7.7+/-8.2 was achieved (p<0.001). Serum levels of eosinophil cationic protein decreased from 22.8+/-19.7 microg/l to 15.4+/-17.5 microg/l, whereas serum tryptase levels did not change. However, there was no significant correlation between the changes in SCORAD, eosinophil cationic protein and tryptase in our cohort. Thus, routine determination of serum eosinophil cationic protein or tryptase levels, in addition to evaluation of disease activity using the SCORAD index, is not recommended in unselected patients with atopic dermatitis.

Adolescent↗
PubMedDate not supplied

Incidence of atopic dermatitis in nursery school children - a follow-up study from 2001 to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. We monitored the incidence of AD and serum total IgE levels annually among nursery school children in Ishigaki Island, Okinawa, Japan, from 2001 to 2004. A total of 1731 children were enrolled. The prevalence of AD ranged from 3.7 to 11% in each year, with no significant difference between boys and girls. 869 children were examined at least twice. 71.6% (53/74) of AD patients regressed spontaneously, whereas 5.5% (44/795) of non-AD individuals developed AD during the 3-year follow-up. Increases in total IgE levels were greater and more rapid in children with long-term AD than in those who had spontaneously regressed, had newly-developed AD or did not have AD. The regression rate of AD was > 70% while new-onset AD occurred at a rate of 3.67%/person year in nursery school children of Ishigaki Island.

Child, Preschool↗
PubMed2001

The ACVD task force on canine atopic dermatitis (XVI): laboratory evaluation of dogs with atopic dermatitis with serum-based "allergy" tests.

Serum-based in vitro "allergy tests" are commercially available to veterinarians, and are widely used in diagnostic evaluation of a canine atopic patient. Following initial clinical diagnosis, panels of allergen-specific IgE measurements may be performed in an attempt to identify to which allergens the atopic dog is hypersensitive. Methodology for these tests varies by laboratory; few critical studies have evaluated performance of these tests, and current inter-laboratory standardization and quality control measures are inadequate. Other areas where information is critically limited include the usefulness of these tests in diagnosis of food allergy, the effect of extrinsic factors such as season of the year on results, and the influence of corticosteroid treatment on test results. Allergen-specific IgE serological tests are never completely sensitive, nor completely specific. There is only partial correlation between the serum tests and intradermal testing; however, the significance of discrepant results is unknown and unstudied. Variation in test methodologies along with the absence of universal standardization and reporting procedures have created confusion, varying study results, and an inability to compare between studies performed by different investigators.

Animals↗
PubMed1996

Glutathione-S-transferase induces murine dermatitis that resembles human atopic dermatitis.

BACKGROUND: The molecular and functional basis of allergen-induced inflammation seen in atopic dermatitis (AD) remains undefined. OBJECTIVE: The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD. METHODS: An inbred strain of mice, BALB/c, when injected peritoneally with 30 micrograms of recombinant Sj26 protein (rSj26), a glutathione-S-transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by serum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen-specific late phase response. RESULTS: Significant responses of rSj26-specific IgE were detected 2 weeks after immunization, and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26-specific positive skin test and epicutaneous patch test could be demonstrated in rSj26-sensitized mice. CONCLUSIONS: These results suggest that rSj26 is capable of eliciting atopic dermatitis-like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen-induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.

Animals↗