6. Atopic disease in childhood
A child with atopy produces IgE antibodies after exposure to common environmental allergens. The atopic diseases (eczema, asthma and rhinoconjunctivitis) are clinical syndromes each defined by a group of symptoms and signs.
Not all children with atopy will have atopic disease or develop symptoms after exposure to an allergen. Both genetic and environmental factors determine the development of atopic disease.
The presence of specific IgE antibodies to environmental allergens is determined with skin prick or radioallergosorbent testing in children with atopy. Test results should be interpreted in the context of the clinical history and further investigations (eg, allergen avoidance or challenge).
Management of atopic disease is frequently symptomatic, but it is important to avoid identified allergen triggers. Immunotherapy may be considered in selected school-age children with severe rhinoconjunctivitis.
Preventing atopic disease in high-risk infants and hindering progression of disease in children with established disease are the areas of active research.
Management of atopic disease should extend beyond symptomatic treatment to identification and avoidance of allergen triggers and, if appropriate, immunotherapy.
T he atopic diseases — eczema, asthma and rhinoconjunctivitis — are the commonest chronic diseases of childhood, affecting one in four Australian children. For most children the symptoms are mild, but those with severe disease are significantly disabled. During the past decade, our understanding of the basic immunology of these diseases has advanced, and this is now beginning to be translated into more effective preventive and management measures.
Atopy and atopic disease
The distinction between atopy and atopic disease is important. A child with atopy produces specific IgE antibodies after exposure to common environmental allergens and is said to be sensitised to that allergen. The presence of specific IgE antibodies is measured by means of a skin prick test or radioallergosorbent testing (RAST). Eczema, asthma and rhinoconjunctivitis are clinical syndromes each defined by a collection of symptoms and signs and are commonly referred to as the atopic diseases. While most children with these conditions are atopic, some are not, and, conversely, some children with atopy may not manifest atopic disease.
Development of atopic disease
Atopic disease occurs when the immune system is dysregulated, resulting in allergic inflammation. Genetic and environmental factors determine the dysregulation and the development of an atopic disease.
Atopic disease has a strong hereditary component — if both parents are affected by an atopic disease (or one parent and a sibling) 40% of offspring will be affected. The genetic influence is multifactorial — no single atopy gene has been identified. It is likely that children who have inherited the “atopy gene(s)” are more likely to become sensitised and to develop allergic inflammation when exposed to the specific environmental influences.1. 2
Environment is an important determinant of atopic disease. Evidence for this includes the regional differences in disease incidence, the recent increase in prevalence of atopic disease, and that children born in a “low atopy” country tend to develop the atopic disease patterns of their host country when they migrate to a “high atopy” country.3
When do environmental factors exert their major effects? There may be a “window of opportunity” in the first few years of life when the developing immune system is particularly susceptible to being directed along an atopic pathway. However, given that adults who migrate can manifest atopic disease after a change in environment, immune changes may also occur at an older age.
Determining which environmental factors prevent or promote atopic disease is complex (Box 1 ). A credible suggestion for the environmental effects is the “hygiene hypothesis”, which postulates that reduced exposure to infectious diseases and microbial products (endotoxin), associated with a “cleaner” lifestyle in urbanised communities, has lessened the immune deviation of the developing immune system to a non-allergic
response.4 - 6 Previously, allergen exposure was thought to be the most important environmental factor influencing this immune deviation. However, the role of allergen exposure in the development of atopic disease is yet to be clearly defined. For example, the “dose” of allergen exposure may be critical — early exposure to high levels of cat allergen may protect against the development of asthma, while low-level exposure may promote asthma.7 Further understanding of the factors that promote or prevent the development of atopic disease is needed, so that primary prevention interventions applicable to communities can be recommended.
The International Study of Asthma and Allergies in Childhood showed that there was marked variation in the global prevalence of atopic disease.3 This variation occurs not only between countries but also regionally within countries, with the highest prevalence being in westernised, industrialised countries. In these countries the prevalence of atopic disease has been rising since the latter part of the 20th century. Australian and New Zealand children have the fifth highest global rates of atopic disease (Box 2 ). Interestingly, recent Australian data in children suggest that the prevalence of asthma has plateaued, while that of eczema and rhinoconjunctivitis continues to increase.8
The first atopic disease to manifest is eczema, which usually commences in early infancy. For up to 40% of children with eczema there is progression to asthma and/or rhinoconjunctivitis, and most develop respiratory symptoms before 5 years of age. This progression in atopic disease is termed the “atopic march”.
There is seldom difficulty in diagnosing atopic diseases. The essential features of the three diseases are:
Eczema — pruritus, the typical appearance and distribution of the rash, and the chronic relapsing course. Important associated features include xerosis, atopy, a family history of eczema, keratosis pilaris, and atypical vascular skin responses.
Asthma — symptoms and signs of intrathoracic airway tract obstruction triggered by specific factors (exercise, viral infection, allergen exposure) and relieved by bronchodilators.
Rhinoconjunctivitis — rhinorrhoea, sneezing, nasal and eye itch and nasal congestion. When symptoms occur seasonally the cause is likely to be allergic, but 40% of children have perennial symptoms, and non-allergic causes need to be considered in the differential diagnosis.
Children with atopic disease are frequently tested by means of a skin prick test or RAST to determine the presence of IgE antibodies specific to common environmental allergens. The indications for performing these tests are given in Box 3. The tests can answer the question “Does this patient have IgE antibodies to a particular allergen of interest?”. However, they do not necessarily answer the question “Is this allergen a cause of the patient’s symptoms?”. This is because positive results of skin prick tests and RAST frequently occur in asymptomatic subjects. To answer the second question, the results of the test have to be assessed together with the clinical history, and, in certain circumstances, in conjunction with either allergen reduction (eg, a trial of dust mite avoidance measures) or allergen challenge.9. 10 However, a negative result of a skin prick test or RAST usually excludes the presence of an IgE-mediated allergy trigger (Box 4 ).
Skin prick testing (Box 5 ) can be done in children of any age, and it is a misconception that the test is less reliable or cannot be interpreted in toddlers and infants. Skin prick test results are given as the mean weal diameter (in mm) measured at 15 minutes. A skin prick test is positive if the weal diameter is 3 mm or greater in the presence of a negative control. When referring patients for skin prick testing, it is important to instruct them not to take antihistamine medication, as this will interfere with the test results. Steroids and