Allergic characteristics of urban schoolchildren with atopic eczema in Ghana

Background Atopic eczema is an increasing clinical problem in Africa. Objective To determine allergic characteristics and to identify possible risk factors for eczema among schoolchildren in an urbanized area in Ghana. Patients and methods Schoolchildren aged 3–16 years with eczema were recruited. For each patient, one to three age‐ and sex‐matched controls were selected. All children completed a questionnaire and were skin prick tested with a panel of allergens. Blood was drawn to determine the total and allergen‐specific IgE. Conditional logistic regression models with the matching factors included in the model were used to calculate the odds ratios and to adjust for possible confounders. Results A total of 52 children with eczema (27 boys and 25 girls) and 99 controls were included. Levels of total IgE were found to be 9.1 (1.1; 78.4) times more often elevated in children with eczema. This association was mainly driven by elevated IgE levels against cockroach antigen. Children with eczema were found to have 2.0 (0.87; 4.7) times more often positive skin prick tests (SPT), but this association diminished to 1.2 (0.40; 3.6) after adjustment for total IgE levels. Frequent washing with soap was identified as a risk factor for the development of eczema among these children. Conclusion Schoolchildren with eczema in Ghana were characterized by elevated IgE levels especially against cockroach antigen. The association between eczema and positive SPT was much weaker suggesting immune hyporesponsiveness of the skin. After adjustment for IgE level, SPT were less suitable to distinguish children with and without eczema.     

Reduction of environmental mites improved atopic dermatitis patients with positive mite-patch tests.

During a series of studies on the involvement of house dust mite antigens in 183 cases of atopic dermatitis, we observed an improvement in two patients following the removal of mites from their environment by means of a thorough housecleaning and replacement of the mattress. Both patients manifested the typical clinical skin lesions of atopic dermatitis and had similar laboratory findings. Although the serum IgE concentrations and specific IgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae were each relatively low, the results of patch tests with these antigens were positive. Thus, a regimen aimed at reducing the presence of house dust mites can produce clinical improvement in a subset of patients with atopic dermatitis who show contact hypersensitivity to mite antigens on skin testing, but negative results on IgE (RAST; radioallergosorbent technique) testing.     

Establishing an allergic eczema model employing recombinant house dust mite allergens Der p 1 and Der p 2 in BALB/c mice

The major house dust mite allergens Der p 1 and Der p 2 are prevalent inducers of eczema. Der p 1 is a cysteine protease disrupting epithelial barriers, whereas Der p 2 functionally mimics the LPS‐binding compound MD‐2 within the TLR4 complex. In this work, we tested the percutaneous sensitizing capacity of recombinant (r) Der p 1 and Der p 2 in BALB/c mice. Mice were sensitized by percutaneous application of low (10 μg/application) and high dose (100 μg) rDer p 1 or rDer p 2, or with rDer p 1 followed by rDer p 2. Allergen‐specific and total IgE antibodies were determined by ELISA. Eczema of BALB/c was classified by the itching score and corresponded to erosions. Infiltrating immune cells were identified by haematoxylin/eosin and Giemsa staining for eosinophils or mast cells, CD3 staining for T lymphocytes. Percutaneous treatments with rDer p 1, but not rDer p 2‐induced specific IgG1. However, cotreatment with rDer p 1 led to increase in anti‐Der p 2 IgG titres. Both allergens elicited skin erosions because of scratching, thickening of the epidermis, and eosinophil and T‐cell infiltration. Our data indicate that recombinant mite allergens in the absence of adjuvant are sufficient for inducing eczema in BALB/c mice. As the enzymatic activity of an allergen might be an important cofactor for specific sensitization via the skin, Der p 1 may act as adjuvant for other allergens too. The presented mouse model is suitable for investigating the mechanisms of allergic eczema.     

Current eczema in children is related to Der f 1 exposure but not to Der p 1 exposure

BACKGROUND: Mite allergen exposure is an important risk factor for specific IgE production and is associated with asthma, hay fever and eczema. Whether these associations are independent of mite species has not been investigated so far. OBJECTIVES: To investigate the influence of exposure to the major house dust mite (HDM) allergens Der p 1 and Der f 1 on sensitization, respiratory symptoms, and especially on eczema and related skin symptoms in 6-7-year-old children. METHODS: In a cross-sectional study in Augsburg (Bavaria, Germany) 1669 school beginners (mean age 6.5 years) were investigated in 1996. The concentrations of Der p 1 and Der f 1 were measured in dust samples from mattresses of 1081 children by enzyme-linked immunosorbent assay. The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and determination of specific serum IgE concentrations by radioallergosorbent test. Information about covariates was taken from questionnaires and interview data. Logistic regression was used to adjust for confounding. RESULTS: The mean concentrations of Der p 1 and Der f 1 were 0.68 and 0.79 microg g(-1) dust, respectively. The relationship between the two species-specific allergens in individual homes was poor (Pearson correlation 0.2). Influencing variables were bedroom-sharing (Der p 1) and social status of the parents (Der f 1). Respiratory diseases were positively associated with both allergen concentrations [odds ratio (OR) between 1.1 and 2.6]. These associations were significant for sneezing attacks (Der p 1 and Der f 1). Reported prevalence of current (in the last 12 months) itchy skin rash was significantly associated with exposure to Der f 1 only (OR 2.4, P < 0.003); also a diagnosis of atopic eczema on the day of investigation was positively associated with Der f 1 only (OR 1.8, P = 0.14). CONCLUSIONS: Studies on the effects of HDM exposure on eczema and allergies should consider specific effects of different mite species. This might have implications on assessment of allergen exposure and consecutive prevention or therapeutic measures.     

Mite allergen (Der p 1) levels in houses of children with atopic dermatitis: the relationship with allergometric tests

Several studies, in particular in adult groups, have evaluated the involvement of mites in the pathogenesis of atopic dermatitis (AD). This still remains controversial. The objective of this study was to determine the level of house dust mites (HDMs) in the beds of a group of children with AD and correlate these levels with their allergometric assessment. Forty-one children with AD underwent allergometric tests (prick test, patch test and radioallergosorbent test, RAST) and the concentration levels of HDMs in their homes were evaluated. Our data show that about half of the children (51%) with AD presented Dermatophagoides pteronyssinus positivity (prick test and/or RAST and/or patch test). Dust was collected in the period October-November from the children's beds, by the same two operators, using a dust-collection device. The dust mite level was tested by an enzyme-linked immunosorbent assay with antibody against Der p 1 allergen. Ten children (24%) presented a Der p 1 concentration > 2 microgram/g of dust (the value assumed to be a risk level for sensitization), 20 (49%) between 0.1 and 2 microgram/g and 11 (27%) < 0.1 microgram/g of dust. In the group with the highest Der p 1 concentration (> 2 microgram/g dust) nine children (90%) presented an allergometric D. pteronyssinus sensitivity, the difference with the other two groups being statistically significant at P < 0.018. The results of the present study show that the highest HDM concentrations were observed in the group with an allergometric D. pteronyssinus positivity (prick test and/or RAST and/or patch test). It is hypothesized that a higher HDM concentration may elicit D. pteronyssinus IgE sensitization and delayed hypersensitivity in children with AD.     

Aggravation of atopic dermatitis‐like symptoms by consecutive low concentration of formaldehyde exposure in NC/Nga mice

Formaldehyde (FA) has been known to be associated with development of asthma (AS) and atopic dermatitis (AD). In this study, we investigated whether FA inhalation would affect the provocation or exacerbation of AD‐like symptoms. Atopic‐prone NC/Nga mice were exposed to low (0.2 ppm) and high (1.0 ppm) concentration of FA by inhalation. Combined exposure to low concentration of FA inhalation and topical house dust mite (HDM) stimulation significantly upregulated HDM‐induced total plasma IgE and IgG2a production, Th1‐, Th2‐, Th17‐related cytokine as well as COX‐2 mRNA expressions in the skin. Interestingly, independent FA inhalation, especially at low concentration (0.2 ppm), increased the skin mRNA expressions of IL‐13, IL‐17E/IL‐25 and COX‐2, even though it failed to induce AD‐like skin inflammation. In conclusion, we suggest that increased skin mRNA expressions of IL‐13, IL‐25/IL‐17E and COX‐2 by independent low concentration of FA exposure might be a key factor to exacerbate HDM‐mediated AD‐like skin inflammation.     

慢性湿疹和皮炎122例斑贴试验结果分析

目的:探讨慢性湿疹和皮炎患者接触性致敏原及其特点。方法:应用斑贴试验分析122例慢性湿疹和皮炎患者接触性致敏原。结果:列前10位的常见致敏原分别是0.1%硫柳汞、5%硫酸镍、7%芳香混和物、1%甲醛、1%肉桂醇、1%促进剂D、1%氯化钴、20%松香、25%秘鲁香油、3%卡巴混和物;引起手部湿疹和皮炎患者的致敏原主要为0.1%硫柳汞和7%芳香混和物,躯干、四肢湿疹和皮炎患者的致敏原主要为5%硫酸镍和0.1%硫柳汞,面部湿疹和皮炎患者的致敏原主要为0.1%硫柳汞和1%甲醛,脐周皮炎患者的致敏原主要为5%硫酸镍。结论:斑贴试验有助于明确慢性湿疹和皮炎患者的接触性致敏原及其性质。     

Environmental associations with eczema in early life

BACKGROUND: Although atopic eczema (AE) is a common disease, little is known about its causes. OBJECTIVES: To investigate the role of dietary and environmental factors associated with the development of AE by the age of 2 years. METHODS: A cohort of children was recruited before birth from a consecutive series of newly pregnant mothers presenting for antenatal care at three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were available for 624 (97%) of the original cohort. AE was defined using components of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed eczema and maternally reported eczema. Exposures of interest were family history of allergic disease, dietary and breastfeeding patterns, family size and exposure to indoor domestic allergens. RESULTS: The cumulative prevalence of AE using the U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The prevalence of maternally reported doctor-diagnosed eczema was much higher (31%, 95% CI 27-35%) and almost half (45%) the mothers reported that their child had ever had eczema (95% CI 41-49%). The relationship between parental atopy, parental history of allergic disease and the child's eczema was consistently stronger for the mothers than the fathers. There was a marked increase in the prevalence of eczema with increasing maternal education and in less crowded homes, associations that remained significant after controlling for other factors. CONCLUSIONS: The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.     

Effect of house dust mite avoidance measures in children with atopic dermatitis

BACKGROUND: House dust mite allergens are associated with atopic dermatitis (AD). OBJECTIVES: The aim of our study was to verify if house dust mite allergen avoidance measures can improve the clinical manifestations of AD in children. METHODS: Forty-one children (mean age 3.9 years) affected by AD associated with high total and/or specific IgE serum levels ('extrinsic' AD) were recruited. Clinical evaluation was performed utilizing the Severity Scoring of AD (SCORAD) index; dust was sampled from the children's beds and tested using an enzyme-linked immunosorbent assay. The study was planned in two parts. In the first part, a placebo-controlled trial of 2 months duration, mite allergen avoidance measures (encasing mattresses and pillows; a weekly hot wash of bedding; frequent vacuum cleaning of living room and bedroom; soft toys and carpets regularly cleaned or removed; no pets allowed) were recommended to group A patients, but not to group B. In the second part of the study, environmental avoidance measures were recommended to initial control group B patients also. One year after the start of the study the amounts of mite allergen in the home and clinical score of AD were measured in both groups. RESULTS: At the end of the first part of the study, significant decreases in major allergens of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) load (from 393 to 94 ng m-2) and concentration (from 1.84 to 0.73 microg g-1 of dust) in children's beds were observed in treatment group A. At the same time, in this group the mean SCORAD index improved significantly (from 33 to 26; P = 0.022). After 12 months, when all patients had used allergen avoidance measures, Der p1 + Der f1 load, concentration and clinical score had improved, reaching similar values in both groups. CONCLUSIONS: Simple mite allergen avoidance measures should be recommended to families with children affected by extrinsic AD in order to control the clinical manifestations and prevent mite sensitization.     

Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis

BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. OBJECTIVES: We therefore performed a randomized controlled study of house dust mite control in patients with this disease. METHODS: Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. RESULTS: At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. CONCLUSIONS: For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.     

Mite-antigen-stimulated cytokine production by peripheral blood mononuclear cells of atopic dermatitis patients with positive mite patch tests

To investigate possible involvement of Th1-type immunoreaction in the development of skin lesions of atopic dermatitis (AD), we measured mite-antigen-stimulated production of IL-2, IL-4 and IFN-γ, using peripheral blood mononuclear cells (PBMC) obtained from 23 patients with AD who developed positive patch test reactions to house dust mite antigens extracted from Dermatophagoides pteronyssinus (Dp). Incubation of these PBMC with the Dp antigen for 72 h produced marked secretion of IL-2 and IFN-γ, but not IL-4, indicating that Dp-specific T cells were found in these patients' circulating peripheral blood and were capable of producing IL-2 and IFN-γ, known as major mediators of the delayed-type allergic reaction. Our study suggests that Thl-type cells may be involved in the development of skin lesions of AD patients with positive patch test reactions to house dust mite antigen.     

Treatment of atopic eczema with oral mycophenolate mofetil

BACKGROUND: Activated T and B lymphocytes are the predominant inflammatory cells in atopic eczema (AE) lesions. Mycophenolic acid, the active form of mycophenolate mofetil (MMF), blocks the proliferative responses of T and B lymphocytes. OBJECTIVES: In this pilot study, we examined the efficacy of MMF (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. METHODS: Ten patients with severe AE (severity index > 50) according to the Severity Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an initial dose of 1 g daily during the first week and 2 g daily for a further 11 weeks. Laboratory examination including full blood count, lymphocyte subset analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline phosphatase, aminotransferases, lactate dehydrogenase and creatinine was performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)-gamma in serum were measured. RESULTS: None of the 10 patients who received MMF discontinued the trial because of lack of efficacy or adverse events. Compared with the baseline, the median scores for disease severity (SCORAD index) improved by 68% during treatment with MMF. The median serum IgE level decreased significantly, from 10,300 kU L-1 before treatment to 7830 kU L-1 after 12 weeks. MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN-gamma and a significant decrease in IL-10, mainly produced by Th2 cells. CONCLUSIONS: The present study demonstrates that oral MMF at a dose of 2 g daily is an effective, safe and well-tolerated immunosuppressive therapy for severe AE in adults.     

Atopic eczema or atopiform dermatitis

Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010. Abstract: Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL‐31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation‐regulated chemokine (TARC) and proliferating‐inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside‐outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen‐specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.     

Topical interferon alpha in atopic eczema

Background On the basis of experimental and clinical data, interferon α might improve pathological alterations in atopic eczema. Systemic treatment with this drug is however cumbersome and fraught with side effects. Objective Since most patients with atopic eczema have only localized disease, we have decided to study the effect of topically applied interferon α in this disease. Design A pilot study was performed on 10 patients, using a single-blind, within-patient comparison. An interferon-α2a gel formulation (150000 IU/g) was studied against triamcinolone acetonide liquor carbonis detergens and bland cremes or gels with a twice daily application to the anticubital fossae over 10 days. Biopsies were taken from 3 patients for evaluation of treatment-induced histopathological changes. Results Improvement of eczema occurred most rapidly with triamcinolone whereas interferon α was as effective as other treatments and vehicle alone. No effect on pruritus was noted with any patient. Only two patients considered interferon α better than liquor carbonis detergens or bland cremes respectively. Mast cell numbers were elevated in all patient biopsies and were lower on the triamcinolone-treated site in only one patient. Conclusion Short-term treatment with topically applied interferon α is thus ineffective in atopic eczema.     

Classification of atopic hand eczema and the filaggrin mutations

Hand eczema is a common disease with various risk factors of which atopic dermatitis is known to be one of the most important. Recently, two mutations in the gene coding for filaggrin, a protein important for the skin barrier, have repeatedly been shown to be associated with atopic dermatitis. Moreover, one study point towards an association between the filaggrin null alleles and the subgroup of patients having both hand eczema and atopic dermatitis. For the remainder of hand eczema patients, still unknown genetic risk factors exist. We propose that in future, classification of atopic hand eczema should distinguish between patients with and without the filaggrin null alleles and to further differentiate between associations with type I allergy, type IV allergy and exposure to irritants, respectively. Furthermore, we suggest future studies of atopic hand eczema to analyse for the filaggrin mutations. We believe this will increase the possibility of subgrouping this otherwise heterogenic disease and thereby enable a better phenotype-genotype characterization of hand eczema. This could improve the preventive initiatives, secure better information of patients about the prognosis for their disease, and possibly enable targeted treatment.