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- Material and methods
Background: The prognosis of atopic dermatitis is usually good, but the risk of developing asthma and allergic rhinitis is very high. The aim of this study was to follow children with atopic eczema up to school age to chart the course of sensitization and development of clinical allergy, as well as to study risk factors of sensitization.
Methods: Ninety-four children with atopic dermatitis were followed up to 8 years of age. The children were examined twice a year up to 3 years of age, and thereafter once yearly. At each visit, a clinical examination was performed, and a blood sample was taken. After 3 years of age, skin prick tests (SPTs) with inhalation allergens were performed at each visit. Information was obtained about atopy in the family, feeding patterns during infancy, symptoms of atopic disease, infections, and environmental factors.
Results: During the follow-up, the eczema improved in 82 of the 94 children, but 43% developed asthma and 45% allergic rhinitis. The risk of developing asthma was higher in children with a heredity of eczema. Presence of severe eczema at the time of inclusion in the study was associated with an increased tendency to produce food-specific IgE. An early onset of eczema was associated with an increased risk of sensitization to inhalant allergens, and development of urticaria. Early allergic reactions to food were associated with later reactions to food, allergic rhinitis, urticaria, and sensitization to both food and inhalant allergens. Early feeding patterns, time of weaning, and introduction of solid food, did not influence the risk of development of allergic symptoms. A large number of periods or days with fever during the follow-up was associated with an increased risk of developing allergic rhinitis and urticaria.
Conclusions: Our results confirm the good prognosis for dermatitis and the increased risk of developing asthma and allergic rhinitis. Development of otherallergic symptoms or sensitization was associated withthe following factors: a family history of eczema, age at onset of eczema and its severity, early adverse reactions to foods, and proneness to infections.
Material and methods
- Top of page
- Material and methods
One hundred children with atopic dermatitis were recruited in Uppsala and Örebro, two middle-sized cities in Sweden. Most of them attended the allergy clinic, but a few were also referred by child welfare clinics when it became known that we wanted to do a prospective follow-up study. Ninety-four of these 100 children (Uppsala 45, Örebro 49), aged 4–35 (median 17.0) months at recruitment, completed the study. The inclusion criteria were pruritic eczema on an area of at least the size of the child's hand, and a duration of the disease of at least 3 months.
The children were examined every 6 months up to 3 years of age and thereafter once yearly up to 7 years of age. At each visit, the child was examined, and a blood sample was taken, and after 3 years of age, skin prick tests (SPTs) with inhalation allergens were performed every year. At the first visit, a questionnaire was filled in about background factors such as heredity of atopy and eczema, symptoms of bronchial obstruction and atopic dermatitis, feeding patterns during infancy, and development of eczema and other possibly allergic symptoms. On the follow-up visits, a written form, based on an interview, was filled in containing questions about exposures and events since the last visit: furry animals in the home; environmental tobacco smoke; number of days with fever (>38.5°C); number of febrile episodes; occurrence of bronchial obstruction, rhinoconjunctivitis, periods with snoring and coughing, and urticaria; severity of eczema, area involved, and treatment; and number of adverse reactions to food as well as the offending foods. All background factors are listed in Table 1. The children were seen at an interval of at least 36 months between the first and the last visit. Moreover, all children were at least 60 months old at the last visit. During the study, the children were examined on 632 occasions, with a mean of 6.7 visits per child.
Table 1. Background factors on admission to study (explanatory factors). Frequencies as percentage (n=94 except for fx5)
|Family history of atopy, single or double||69|
|Family history of atopic dermatitis, single or double||58|
|Feeding patterns during infancy|
|Breast-feeding ended before 6 months of age||53|
|Introduction of cow's milk-based formula|
|before 4 months of age||44|
|Introduction of hen's egg before 12 months of age||69|
|Introduction of fish before 7 months of age||35|
|Onset of eczema before 4 months of age||51|
|Eczema score 6–8 on first examination||52|
|Any adverse food reaction before 36 months of age||63|
|Adverse reaction to cow's milk, soybean, hen’s egg, or fish|
|before 36 months of age||42|
|Positive fx5 (n=87) before 36 months of age ||61|
In analysis of the data, the follow-up time was divided into three periods for simplification. One visit in each period was evaluated. These three index visits were as follows:
Period 1. The first index visit was the inclusion visit. The children were 4 months to 3 years old, mean age 18.3 months.
Period 2. The first visit as soon as possible after the age of 3 years. The children were 3–5 years old, mean age 42.0 months.
Period 3. The last visit in the study; on this occasion, the children were 5–8 years old, mean age 85.5 months.
Definitions and methods
Atopic dermatitis was defined as pruritic, chronic, or chronically relapsing dermatitis, with typical features and distribution, as suggested by Hanifin & Rajka ( 7). A score was used to evaluate the severity and extent of involvement (graded 0–3 each), and the treatment (grade 0–2), making a maximal score of 8 ( Table 2). The total eczema score at each visit was plotted, and an eczema coefficient was calculated with a regression line through each score value. Bronchial asthma was defined as three or more episodes of bronchial obstruction diagnosed by a physician. Allergic rhinoconjunctivitis was defined as development of rhinitis and conjunctivitis at least twice after exposure to a particular allergen and unrelated to infection. Urticaria was defined as a history of typical symptoms. Atopic heredity was regarded as present if at least one of the family members had shown symptoms of atopic dermatitis, bronchial asthma, or allergic rhinoconjunctivitis.
Table 2. Sum of scores for severity, extent of involvement, and treatment was used as eczema score in this study
|Severity (mean of worst area corresponding to size of child's hand)|
|1: superficial, pale, dry, no obvious itch|
|2: red, moderate itch|
|3: red with papulovesicles, sometimes oozing or infected; severe itch|
|1: area less than child's hand|
|2: area corresponding to 1–4×size of hand of child|
|3: larger area|
|Treatment during last week|
|0: no treatment|
|1: daily treatment with emollients and/or group 1 steroid|
|2: at least five treatments with steroid stronger than group 1|
SPTs were performed as single tests on the forearm of the child with the following allergens (Allergo-logic Laboratory, Copenhagen [ALK], Copenhagen Denmark, 10 SQ/ml): birch, timothy, and mugwort pollen; cat, dog, and horse epithelia; Dermatophagoides farinae and D. pteronyssinus; and Cladosporium herbarum. In addition, extracts of egg and fish (ALK) and commercial skimmed milk were used for SPT when needed. Histamine hydrochloride 10 mg/ml was used as a positive control. A mean wheal diameter of at least 3 mm after 15 min was regarded as a positive test.
After venepuncture and coagulation, blood serum was separated and stored at −20°C pending analysis. Determinations of allergen-specific IgE antibodies to individual allergens and to a panel of six food allergens (fx5 containing allergens from hen's egg, cow's milk, cod, wheat, peanut, and soybean) or a panel of inhalant allergens (Phadiatop) were performed with Pharmacia CAP-RAST, according to the manufacturer's instructions. In the presentation of data, explanatory and outcome parameters are used. As explanatory para-meters, the choice fell on family history of atopy and eczema, feeding pattern during infancy, age at onset of eczema and the severity of eczema at the first visit, food reactions before 36 months of age, a positive fx5 before 36 months of age, presence of furry animals at home, exposure to indoor tobacco smoke, 2 or more days with fever (≥38.5°) in the last month preceding at least two visits, and more than three febrile episodes 6 months before any visit. Theseparameters were chosen because they often are discussed asbeing allergy risk factors.
Our outcome parameters ( Table 3) included asthma, urticaria, allergic rhinoconjunctivitis, adverse food reaction after 36 months of age, less than average healing of the eczema, eczema score of ≥3 at the last visit, positive SPT or RAST for inhalation allergens after 36 months of age, and a positive fx5 after 36 months of age.
Table 3. Outcome parameters
|Urticaria at least once||51|
|Allergic rhinoconjunctivitis at least twice||50|
|Adverse food reaction after 36 months of age||56|
|Less than average healing of eczema,|
| according to eczema coefficient||50|
|Eczema score 3 or more at last visit||49|
|Positive SPT or RAST for inhalation allergens|
| after 36 months of age||78|
|Positive fx5 after 36 months of age (n=84) ||44|
All explanatory factors were analyzed against outcome parameters, using ORs with 95% confidence intervals. To identify the factors that best predicted the outcome parameter, asthma development logistic regression was used. The selection method was backward stepwise elimination with the likelihood ratio. The analyses were performed with the SPSS program for Windows, Release 8.0.
All parents of the participating children gave their oral consent after receiving oral and written information. The ethics committee of the Medical Faculty in Uppsala and Örebro approved the study.
- Top of page
- Material and methods
Our patient material was selected to include infants and young children with mild-to-severe eczema, in order to study the risk patterns of sensitization and development of clinical symptoms of allergy. These 94 children were followed until they were 5–8 years of age. We used our own eczema scoring system, since, at the time our study was planned, no such system was generally accepted. Our system, like most others, takes into consideration the extent and severity of eczema ( 8–11). Unlike most other systems, we also included the treatment of the eczema before each visit, since the type and intensity of treatment influence at least the severity of the eczema. Different grading systems are not interchangeable, and our scoring system therefore cannot easily be converted into other systems ( 12).
In our study, we confirmed that the prognosis of childhood eczema is usually good ( 6, 13).
Although not all infants with eczema who fulfill the criteria of atopic eczema have positive skin tests and/or RASTs, the eczema usually is a marker of an atopic disposition that is accompanied by a high risk of early sensitization to allergenic foods and of later sensitization to airborne allergens ( 5, 14–22). This high risk was confirmed by our study. Of 94 children with eczema, 50% developed allergic rhinitis and 47% developed asthma before 7 years of age. Moreover, a further 18% were sensitized to inhalant allergens, but had not yet developed clinical symptoms from the airways. Although we included no control group of children without eczema, these figures are six to eight times higher than those reported in Sweden for allergic rhinitis and asthma among children in this age group ( 4–6, 23). An early onset of IgE-mediated food allergy in an infant with atopic eczema indicates the presence of a Th2-dominant lymphocyte pattern with a cytokine profile facilitating an IgE response to environmental antigens. It is therefore not surprising that an early manifestation of IgE-mediated food allergy is accompanied by a very high risk of sensitization to airborne allergens and a high risk of developing asthma and allergic rhinitis ( 24). Only 17 of the 69 children (25%) with symptoms of food allergy before 36 months of age failed to develop asthma or allergic rhinitis during the study.
Atopic heredity was associated with a significantly increased risk of becoming sensitized to airborne allergens, but not of developing clinical allergy. This may seem remarkable, but the atopic trait affects the likelihood of producing allergen-specific IgE, and not necessarily organ or tissue sensitivity and reactivity, which are influenced by local factors. It is probable that some of the sensitized children in our study group will develop allergy symptoms later. As children with atopic heredity had ORs of >1 for asthma and allergic rhinoconjunctivitis, it is possible that a significant association could have been found if a larger number of children had been included.
Other risk factors included early onset of eczema and initially severe eczema. This has also been reported in other studies ( 24, 25). Severe eczema, but not an early onset, was associated with sensitization to food allergens. This is in agreement with other studies showing that food allergy occurs more often in children with severe eczema ( 25, 26). The increased frequency of urticaria was observed among children with food reactions but also among children with increased rate of infections, indicating that urticaria may be caused by both allergic and nonallergic mechanisms.
It may also seem remarkable that such environmental factors as keeping furred animals and exposure to tobacco smoke were not associated with an increased risk of developing allergy and asthma, since these factors in many other studies are regarded as major risk factors for asthma and allergy ( 16, 27–32). The most likely explanation is that families with severe atopic problems avoid keeping furred animals and smoke less than the population in general and probably also less than families with less severe atopic problems. The type of infant feeding seemed to influence very little the risk of developing allergy and asthma, but the design of our study is not optimal for evaluation of food as a risk factor since all children suffered from atopic eczema.
In conclusion, our study has confirmed the good prognosis of childhood eczema, but also the increased risk of developing respiratory allergy. This risk is especially high in children with early onset of food allergy. We found no characteristics other than mild eczema, and late onset of eczema in the children under study, who did not become sensitized to airborne allergens before school age. Sensitization to individual food and airborne allergens will be reported in a forthcoming paper.