Determinants of total and specific IgE in infants with atopic dermatitis

ETAC (Early Treatment of the Atopic Child), a multi-centre predominantly European study to investigate the potential for cetirizine to prevent the development of asthma in infants with atopic dermatitis has completed enrolment: 817 children have been randomised to 18 months' treatment with either active or placebo and a subsequent 18 months of post-treatment follow-up. Results of the therapeutic effects will not be available for some time, but the study has provided an opportunity to investigate influences on sensitization to allergens in a large cohort of 1-2 years olds with already established atopic dermatitis, resident in different countries and in different environments.
The study shows that in infants with atopic dermatitis, raised serum total IgE has significantly different determinants from that a specific allergen sensitization. In infancy, increased total IgE is more affected by factors increasing risk of intercurrent infection and non-specific airway inflammation, such as environmental tobacco smoke exposure (p < 0.001) and the use of gas cookers (p=0.02). Specific allergen sensitization as represented by detectable IgE antibodies is influenced primarily by allergen exposure. In Sweden, low level exposure to allergens is associated with reduced specific allergen sensitization rates even though the infants already have atopic dermatitis.     

Specific IgE antibodies and serum eosinophil cationic protein in children with atopic dermatitis alone

Both eosinophils and specific immunoglobulin E (IgE) to foods and mites have been considered involved in the pathogenesis of atopic dermatitis (AD). The relationship between eosinophils and specific IgE, however, remains to be elucidated. Blood eosinophil counts, serum eosinophil cationic protein (ECP) and IgE to egg white, cow's milk, soybean, rice and Dermatophagoides pteronyssinus (Dp) were measured in subjects with AD alone or bronchial asthma (BA) alone. Subjects with positive IgE titers (Pharmacia radioallergosorbent test (RAST) units > 0.7) of one or more items were defined as RAST-positive. Immunoglobulin E titers to egg white, cow's milk and soybean of subjects with AD were high in early childhood and declined with aging, whereas the titers of subjects with BA were negative or low. Immunoglobulin E titers to Dp were elevated after 1 year of age in both disease groups. Eosinophil cationic protein (ECP) levels and blood eosinophil counts in the AD and BA groups were significantly higher than those of non-atopic controls. No difference in ECP levels or blood eosinophil counts were observed between RAST-positive and negative groups. It is concluded that IgE to foods such as egg white, cow's milk and soybean might have a role in the pathogenesis of AD of young children, while IgE to mites might be involved in older children. Eosinophils may also participate in AD. However, different mechanisms may be responsible for the rise in specific IgE and high ECP levels and blood eosinophil counts.     

血清特异性IgE和IgG检测在儿童特应性皮炎过敏原诊断中的应用

目的探讨血清特异性IgE和IgG检测在儿童特应性皮炎过敏原诊断中的应用和意义。方法对64例患特应性皮炎的儿童,采用酶联免疫方法检测血清中食物过敏原的特异性IgG,同时采用免疫印迹方法检测血清中食物过敏原和吸入性过敏原的特异性IgE。结果食物过敏原特异性IgG和特异性IgE的检测结果不一致(P<0.01),食物过敏原特异性IgG的总阳性率为93.75%,主要食物过敏原是牛奶和鸡蛋。食物过敏原特异性IgE的总阳性率为46.88%,主要食物过敏原是鸡蛋和鱼虾蟹。吸入性过敏原特异性IgE的总阳性率为34.38%,主要过敏原是尘螨和霉菌。在0～1岁的特应性皮炎患儿中,以食物过敏原特异性IgE阳性多见;1岁以上的患儿吸入性过敏原特异IgE阳性多见,同时合并呼吸道过敏症状增多(P均<0.05)。结论食物过敏原和吸入性过敏原均是引起儿童特应性皮炎的重要原因。联合测定食物过敏原的特异性IgE和特异性IgG是变态反应性皮肤病患儿诊断食物过敏原的有效方法。尽早采取有效的环境控制,对治疗儿童特应性皮炎和预防呼吸道过敏性疾病的发生非常重要。     

Staphylococcal enterotoxin-specific IgE antibodies in atopic dermatitis

BACKGROUND: The authors clarified the clinical significance of the measurement of serum concentrations of specific IgE antibodies to staphylococcal enterotoxin (SE) A- and SEB in atopic dermatitis (AD). METHODS: The serum concentrations of SEA- and SEB-specific IgE antibodies in 140 pediatric patients with AD were measured with an immuno CAP -radioallergosorbent test system (RAST). To check the cross-reaction of specific IgE antibodies to SEA/SEB and other allergens, the CAP RAST fluorescent enzyme immunoassay inhibition test was performed. RESULTS: Forty-seven patients (33.6%) tested positive for either SEA- or SEB-specific IgE antibodies. School children showed higher positive rates of SEA/SEB-specific IgE antibodies than infants or young children. The patients with severe AD and those with exacerbation of symptoms in summer, had higher positive rates of SEA/SEB-specific IgE antibodies than patients with mild AD or those with exacerbation in winter. In addition, the positive rates of specific IgE antibodies to both dog-dander and cat-dander were higher in patients with positive SEA/SEB-specific IgE antibodies than in patients with negative ones. No cross-reactions occurred among specific IgE antibodies to SEA/SEB and dog/cat dander with one patient's serum, which had positive IgE-specific antibodies against cat/dog dander and SEA/SEB. The positive rate of SEA/SEB-specific IgE antibodies in the patients with dogs and/or cats as pets was 48.4%, which was higher than in those with no pets. CONCLUSIONS: Atopic dermatitis patients who exhibit high positive rates of SEA/SEB-specific IgE antibodies were found to be school children, severe cases, cases with high serum concentrations of total IgE, cases with exacerbation in summer, and cases with dogs and/or cats as pets. The measurement of serum concentrations of specific IgE antibodies to SEA and SEB, thus has some value for evaluating AD patients.     

Does the severity of atopic dermatitis correlate with serum IgE levels?

Recent studies suggest an association between atopic phenotypes and serum IgE levels. In contrast to asthma, this association has not been proven for atopic dermatitis. For 345 children (mean age 2.9 years), we investigated a correlation of the severity of eczema (defined by SCORAD score) and serum IgE levels. Additionally, the data was analyzed for differences between children with high and low SCORAD quartile. Parameters such as genetic background, the prevalence of other atopic phenotypes such as bronchial asthma, allergic rhinoconjunctivitis, and allergic sensitization were recorded. Our results indicate a significant correlation between SCORAD and serum IgE levels (R = 0.31, p < 0.001), but the standard deviation was large. Children with atopic dermatitis showed a high prevalence of sensitization to foods independent of the IgE levels; children with high SCORAD levels showed a sensitization to aeroallergens significantly more often (p < 0.02). No differences were found in prevalences of atopic family background, or a number of additional atopic symptoms such as asthma and allergic rhinoconjunctivitis. These results suggest that serum IgE levels seem to correlate with the degree of eczema. Children with severe atopic dermatitis and high IgE levels are at risk for sensitization to food allergens and aeroallergens.     

Changes in serum lactate dehydrogenase activity in children with atopic dermatitis

Background: In recent years an increase has been seen in the number of patients with severe atopic dermatitis (AD) accompanied with generalized typical eruptions. Some markers indicating the severity of the disease and symptom changes are very useful, and therefore the purpose of the present study was to investigate serum lactate dehydrogenase (LDH) as such a marker. Methods: A total of 58 children with AD were enrolled. The severity of the disease was graded on the basis of the extent of eruptions and the severity of atopic symptoms. The fraction of serum LDH, number of eosinocytes in the peripheral blood, and serum IgE levels were also determined. Results and Conclusion: There was a close correlation between the severity of cutaneous symptoms and serum LDH activity, and between severity and eosinocyte count, but no relationship was seen between serum IgE levels and severity of the disease. The aforementioned factors were determined in a time‐related way. As the patients' condition improved, serum LDH activity tended to decline, but there were no consistent changes in eosinocyte count in the peripheral blood or serum IgE level. On LDH isozyme the levels of LDH4 and LDH5 were high. Tissue showed high LDH activity, especially in epidermides. These results suggest that serum LDH activity is a useful marker.     

Comparison of fecal microflora in children with atopic eczema/dermatitis syndrome according to IgE sensitization to food

Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early infancy. In several intervention studies a beneficial influence on AEDS course of certain intestinal bacteria, administered as 'probiotics', has been described. To evaluate the possible role of the natural intestinal microflora in children with allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to food allergens, children with food allergy (AAEDS, n = 68) have been compared with children without detectable food allergy (NAEDS, n = 25). All children (n = 93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who were treated as inpatients in 2003 in a dermatological hospital were included. The correlation between fecal microflora, parasites and specific immunoglobulin E (IgE) antibodies against common food allergens was analyzed. A similar composition of intestinal microflora in children with AAEDS and NAAEDS was found. The food allergens that were most frequently detected were egg white, cow milk, casein, peanut and hazelnut. Furthermore, a significant association between IgE sensitization against important food allergens and components of the fecal microflora could not be demonstrated. With aging changes occur in the intestinal microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was found. The composition of natural intestinal microflora in children with AAEDS and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal microflora with regard to the development of infant (food) allergy in children with AEDS. The possible consequences for allergic diseases later in life require further investigation.     

Sensitization to food and airborne allergens in children with atopic dermatitis followed up to 7 years of age

Previously we investigated the eczema prognosis and the risk of developing allergic asthma and rhinitis in a cohort of 94 children with atopic dermatitis. In this second study on the same cohort we address the development of sensitization to foods and airborne allergens, risk factors and, the question whether children with atopic dermatitis who will not become sensitized can be recognized early. Children with atopic dermatitis were followed up regularly from infancy or early childhood to 7 years of age with clinical examination and blood sampling. After age 3, skin prick tests with inhalation allergens were performed yearly. In most children both clinical allergy and sensitization to egg and milk were transient but those to peanut were persistent. Eighty per cent of the children became sensitized to airborne allergens and 75% of them noticed symptoms when exposed. Heredity for atopy and eczema, sensitization to hen's egg, and early onset of eczema entailed an increased risk of becoming sensitized. Children never sensitized had late onset of eczema and less heredity for atopic disease but did not differ in other respects from the sensitized children.     

Food hypersensitivity in two groups of children and young adults with atopic dermatitis evaluated a decade apart

There is an impression that children today are experiencing allergic reactions to an increasing variety of foods. We compared two separate groups of children and young adults with atopic dermatitis evaluated a decade apart and found no difference in sensitization rates or overall clinical reactivity to a variety of foods. Allergies to egg, milk, wheat, soy, peanut, tree nuts, and seafood continue to account for ≈ 90% of food‐allergic reactions over the past decade.     

患者治疗教育对特应性皮炎患儿生活质量的改善作用

目的评估患者治疗教育对特应性皮炎(AD)患儿生活质量的改善作用。方法入组AD患儿109例,分为患者治疗教育干预组53例和对照组56例。干预组在常规治疗基础上对患者进行治疗教育,对照组只进行常规治疗;3个月后比较两组疾病严重程度和患儿及家庭生活质量的差异。结果与对照组相比,干预组AD患儿的SCORAD评分显著降低,差异有统计学意义(P=0.003);干预组患儿的生活质量(IDQOL和CDLQI指数)显著改善(P=0.004);两组患儿家庭生活质量(DFI)差异无统计学意义(P=0.492)。结论患者治疗教育有助于改善AD患儿症状及生活质量。     

Patterns of sensitization in infants and its relation to atopic dermatitis

Longitudinal studies in infant populations using validated diagnostic criteria of atopic dermatitis and sensitization are rarely reported, and disease definitions, testing procedures, age of study population and evaluation of objective markers vary between countries and studies. The objectives of this prospective birth cohort study were to investigate: (i) the prevalence, the cumulative incidence and the pattern of transient and persistent sensitization to common food- and aeroallergens in unselected infants, (ii) the association between sensitization and the development of atopic dermatitis (AD) and (iii) the association between selected perinatal risk factors with respect to AD and post-natal sensitization. During a one-year period a cohort of 562 unselected newborns was established and followed up at the age of 3, 6, 9, 12 and 18 months of age. At all time points infants were examined clinically and by histamine release (HR), total- and specific immunoglobulin E (IgE) and skin prick test (SPT). Sensitization ever to > or =1 allergen at 18 months of age was 59%, 50% and 6% using HR, IgE and SPT, respectively. A transient sensitization to > or =1 allergen was found in 47%, 42% and 4% and a persistent sensitization in 17%, 10% and 3%, respectively. Sensitization to environmental allergens was frequently observed in infancy when testing with HR and IgE. Results of SPT gave much lower frequencies. Reactivity to foods was more frequent than to aeroallergens. The dominant pattern was low-level transient sensitization. This is important to know when sensitization tests are used in the course of examination of infants with eczematous skin diseases. Specific definitions of sensitization like persistent reactivity, high-level sensitization and poly sensitization were clearly associated with AD. A maternal history of AD was a valuable tool in predicting AD in early infancy; a similar finding was less obvious with regard to post-natal sensitization. Cord-specific IgE and cord-HR positive reactivity did not prove better tools than cord-total IgE in predicting AD within the first 18 living months.     

Antigen specific cytokine response in pediatric patients with atopic dermatitis

The physiopathology of atopic dermatitis (AD) has still to be elucidated. T effector cells with cutaneous homing receptors or T-cell derived cytokines have been assumed to be implicated in the pathogenetic mechanisms in AD and to be responsible for the different immunologic responses of patients. In fact, the large majority of AD patients display high IgE levels while others do not develop an abnormal IgE response. Although, there are not significant clinical features characterizing the two different groups, patients with normal IgE belong to a younger age range, raising the possibility that the hypothesized dichotomy of AD might be due to age. In the present study we included 172 outpatient children attending the Pediatric Department of our institution. Serum IgE levels and percentages of peripheral T lymphocytes expressing the cutaneous homing antigen (CLA) were evaluated and results were analyzed in relation to the activity of the disease (SCORAD index) or age. In the overall patients, the IgE levels increased significantly with age (0-1 yr: 19.50 IU/ml; 1-3 yr: 62.0 IU/ml; 3-8 yr: 96.0 IU/ml; >8 yr: 148.5 IU/ml; p<0.001) and with the severity of the disease (SCORAD low: 46.80 IU/ml; medium: 42.90 IU/ml; high: 148.5 IU/ml; p=0.01). Percentages of CLA+ peripheral T lymphocytes also increased with age (0-1 yr: 3.3; 1-3 yr: 4.85; 3-8 yr: 10.6; >8 yr: 12.5; p<0.001), although they were not significantly different in patients with different SCORAD (p=0.89). We further investigated the cellular immune response to a specific antigen in 25 subjects, matched for age, SCORAD, and CLA+ T-cell percentages. Among them, 13 patients had casein serum specific IgE and 12 had no evidence of casein sensitization. Peripheral blood mononuclear cells were kept in short-term culture with endotoxin-free casein fractions and IFN-gamma, TNF-alpha, IL-5, IL-10 cytokine-producing cells were detected by ELISpot. Statistical analysis showed significant higher numbers of TNF-alpha- or IL-10-producing cultures (stimulation index >3) in the 'allergic' patients than in the milk tolerant subjects (p=0.01 and 0.05). The analysis of individual responses confirmed this finding but also provide evidence of a significant increase in IFN-gamma-producing cells (p=0.05) induced by casein stimulation in the group of 'non-allergic' children. Our data showed that immunologic parameters as IgE levels or CLA+ T cells in AD pediatric patients are influenced by the age, confirming that age could represent a bias in the analysis of immune response in those patients. Although, we demonstrated in children with AD the existence of different cytokine patterns of the lymphocyte response that could account for the different immunologic features between the two hypothesized forms of AD, which are not dependent on age.     

Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis

In recent years, the atopy patch test (APT) has been suggested as an addition in the allergological work‐up of children with atopic dermatitis (AD) and suspected food allergy. We initiated a prospective clinical study in children with AD younger than 3 yr, to evaluate the additional clinical value of the APT next to our own standardized allergological work‐up in case of a suspected food allergy. One hundred and thirty‐five children were included in the study. They were tested using the skin application food test (SAFT), the APT and measurement of specific IgE. The allergens used in the skin tests were freshly prepared food stuffs and included commercially available cow’s milk (CM), the egg white of a hard boiled hen’s egg and mashed peanuts in a saline solution. Allergy was defined using a flowchart incorporating the results from the SAFT, oral challenges (OCs) and elimination and (re)introduction periods. To determine the additional value of the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and used an exact binary logistic analysis to evaluate the simultaneous effects of the APT and measurement of specific IgE, calculating mutually adjusted odds ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of our study population. Positive SAFT reactions were observed in 14% (peanut), 16% (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not observe a significant additional value of the APT for the diagnosis of CM or egg white allergy, but we did find a significant additional value for the diagnosis of peanut allergy (OR = 11.56; p < 0.005, 2‐sided). In clinical practice this statistically significant value does not exclude the need for OC and controlled elimination and (re)introduction periods due to the presence of false‐negative as well as false‐positive results in the APT. In conclusion, we could not find enough support for the current addition of the APT to our standardized allergological work‐up in young children below the age of 3 yr with AD and suspected food allergy. At the moment the additional value of the classical delayed‐type APT next to the SAFT seems to be very limited at best in this study population and does not justify the time‐consuming nature of the skin test.     

Reduced plasma c-AMP levels in children with atopic dermatitis

Plasma levels of cAMP and serum concentrations of IgE have been determined in children with acute atopic dermatitis (AD) and in a healthy control group, to illuminate the pathophysiological mechanisms that cause AD.
There were significantly lower plasma levels of cAMP (P < 0,001) and significantly higher levels of serum IgE (P < 0.004) in children with AD, in comparison with a healthy control group. It is possible that defective control of c-AMP levels could contribute to the immunopathogenesis of AD and monitoring levels may be of value in the clinical evaluation of the disease.