Epidemiology and natural historical past of atopic health conditions

The word atopy (Greek: atopia, out of place) refers to an inherited tendency to produce immunoglobulin E (IgE) antibodies in response to small amounts of common environmental proteins such as pollen, house dust mite, and food allergens. The presence of atopy in an individual is associated with an increased risk of developing one or more of the atopic diseases – atopic dermatitis, asthma, and allergic rhinoconjunctivitis/hay fever (and food allergy). However, atopy can be present in the form of asymptomatic sensitization to one or more allergens, which means that an individual with confirmed allergic sensitization does not exhibit clinical allergy. Conversely, an atopic disease can be present in a non-sensitized individual (e.g. in non-atopic asthma). Sensitization is common in the atopic diseases of childhood and is less frequent in adults with atopic disease, particularly in those with adult-onset atopic disease (1). Asymptomatic sensitization to aeroallergens, however, is a strong predictor for future development of allergic symptoms, while allergic symptoms in non-sensitized subjects are a much lower risk factor for subsequent sensitization (2).

The allergic march refers to the natural history of atopic disorders. The allergic march concerns the development of atopic dermatitis and concomitant sensitization to food and aeroallergens in early childhood, progressing to asthma and allergic rhinitis in later childhood or adult life (3).Typically, the child develops atopic dermatitis in the first months of life accompanied by sensitization to cow’s milk, egg, or peanut, and sometimes also vomiting, diarrhoea, or anaphylaxis in relation to ingestion  szkoleniakursydladoroslych of these foods beginning around the age of 6–12 months. This is followed by sensitization to indoor allergens such as house dust mite, cockroach, and furred pets. Within the first 2 years of life the child develops recurrent episodes of wheezing, mostly in conjunction with viral respiratory tract infections such as respiratory syncytial virus and rhinovirus (4). After this age wheezing episodes become more frequent and start to occur in between infections, requiring continuous treatment with asthma medication, and now can be said to have manifested asthma. Later in childhood, allergy to outdoor allergens develops and allergic rhinoconjunctivitis occurs in relation to exposure to grass and tree pollen. At the same time, eczema and sensitisations to food wane, but cross-reactions to nuts and fresh fruits and vegetables may develop and give rise to oral allergic manifestations. Despite the teenage years being a time when asthma symptoms may disappear or become less pronounced, after some symptom-free years, skin and respiratory symptoms return in a subset. In young and middle adulthood, respiratory and skin manifestations are more closely related to occupational exposures, lifestyle, and tobacco smoking, so that, for instance, hand eczema or asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) develops in relation to these exposures. In late adulthood, allergic symptoms generally become less frequent and tend to disappear but in some, new-onset allergy or asthma may develop in old age (5).

In childhood the incidence of atopic manifestations is typically higher among boys, but this tendency changes in adolescence and in adulthood, during which girls become more symptomatic (6). Although the skin sensitization occurring in atopic dermatitis appears to be the trigger for the subsequent development of the other allergic conditions, the progression is not uniform in all atopic children. Allergic manifestations can develop at any point in life. Many will experience only one or perhaps two atopic manifestations and the development of these can be interspaced by several years; therefore, it is not uncommon that an adult with ‘new-onset’ asthma is unable to remember whether he or she had asthma or eczema in childhood. In some children, the sequence of events is reversed so that asthma precedes the development of eczema, and sometimes symptoms occur simultaneously, rendering the age of onset of the different disorders indistinguishable. Accordingly, the severity of the atopic syndrome varies highly between affected individuals and the course of the disease depends on a dynamic interplay between many innate and triggering factors.The discovery of filaggrin gene mutations as a predisposing factor for atopic dermatitis and subsequent asthma and sensitization in the context of eczema has redefined our view on the allergic march (7). The atopic diseases can now be viewed upon as causally related conditions – rather than sequentially occurring manifestations of the same underlying disease state – with atopic dermatitis and filaggrin mutations being a prerequisite for the development of the other atopic diseases, particularly asthma (8).Only few prophylactic interventions have been shown to significantly influence the risk of developing atopic diseases in the long run. The advent of filaggrin gene mutations holds promise that progression of the allergic march from atopic dermatitis to asthma can be halted by treating the skin barrier defects in infants and very young children (9).

Atopic dermatitis is primarily a disease of early childhood. About 20% of all children develop symptoms of atopic dermatitis at some point in their lives (10). Half of these develop symptoms within the first year of life with 95% experiencing onset below 5 years of age. The majority outgrows atopic dermatitis in childhood or early adolescence, but around 25% continue to have eczema into adulthood or experience a relapse of symptoms after some symptom-free years. Up to one fourth of subjects with moderate to severe atopic dermatitis in childhood will develop hand eczema to various degrees in adult life (11).About 30% of all children with atopic dermatitis have food allergy. The allergens involved are typically cow’s milk and egg with other foods also being common, for example, soy, wheat, and fruits. However, intake of foods is rarely the cause of exacerbations in atopic dermatitis and many patients with atopic dermatitis are sensitized to foods without this being involved in the activity of the disease.The risk of other atopic diseases, primarily asthma and hay fever, is markedly increased in children with atopic dermatitis. A child with moderate to severe atopic dermatitis has a 50% risk of developing asthma, either concomitantly or in later life, whereas the risk of developing hay fever is as much as 75% (12).

Many patients tend to confuse real food allergies with non-allergic food reactions, such as food intolerance, which gives an impression in the public that real IgE-mediated food allergy occurs more frequently than is the case.More than 170 foods have been reported to cause IgE-mediated reactions, but the allergens most commonly involved are cow’s milk, egg, nuts, fish, and shellfish (13). Food allergy typically develops in the order in which the individual is exposed to the specific food. Therefore, allergy to cow’s milk develops in early childhood followed by allergy to egg (13). In older children, allergy to wheat and fresh fruit develops, and in adults, the most common food allergies relate to nuts and shellfish as well as food allergy due to cross-reactivity with pollen. Self-reported symptoms suggestive of allergy to these foods occur in about 10–15% of children and adults. However, the prevalence of confirmed food allergy is only about 3–5%. Food-induced anaphylaxis is a very serious event that occurs in less than 0.1% of the general population.

Most children with food allergy will eventually tolerate cow’s milk, egg, soya, and wheat, but far fewer will eventually tolerate tree nuts and peanut. The time course of food allergy resolution in children varies according to the foodstuff and may occur as late as the teenage years. For example, in children diagnosed with egg allergy in early life, two thirds will be tolerant by school age and most with allergy to cow’s milk will tolerate cow’s milk in adolescence. Risk factors for persistence of egg allergy are a high initial level of egg serum IgE, the presence of other atopic diseases, and the presence of an allergy to another food. With avoidance diet, up to 15–20% of children will remain allergic and the severity of the reactions may increase with time. In these severe cases of egg allergy, it becomes more difficult to adhere to the avoidance diet, with a considerable decrease in patients’ quality of life (14). Induction of oral tolerance can be regarded as a therapeutic option for IgE-mediated egg allergy. Omalizumab (anti-IgE) might become a therapeutic option for food allergy, not only to prevent allergic reactions after a contact with egg, but also as a complementary treatment to oral tolerance induction for egg allergy, with the purpose of reducing adverse reactions (14). Administration of influenza vaccine to children with egg allergy is safe in children that do not manifest severe reactions after egg intake, and in children who tolerate cooked egg. The triple viral vaccine (MMR) can be given to egg-allergic children with no increased risk. Different medicinal products are formulated with egg proteins, and therefore should be avoided in children with egg allergy (14). In children, a drop in serum IgE levels over time is often a marker of the onset of tolerance to the food. In contrast, for some foods, the onset of allergy can occur in adult life, and the food allergy may persist despite a drop in IgE levels over time. A high initial level of serum IgE against a food is associated with a lower rate of resolution of clinical allergy over time. Food allergy that develops in adulthood has a much more unfavourable prognosis and, as a rule, will persist throughout life.


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