Atopic diseases
Epidemiology of atopic diseases
Populations are sensitized to different environmental allergens and individuals have different patterns of sensitization to allergen components, which all contribute to the varied clinical picture of allergic conditions.16,36,40–42,59–71 In general, the incidence and severity of food allergy has increased during the past decades in Western World,70,72 however there are large geographical differences in the prevalence of food sensitization, food allergies, and allergen cross-reactivity.70,73–75 In school-aged children, for example, the prevalence estimates of food sensitization vary from 11.0% to 28.7% and for food allergy from 1.0% to 5.6% across Europe.70,73–75
The prevalence of atopic dermatitis (AD) varies from 10–20% depending on the age and region.40,76–78 Individuals with AD have a 2–3 fold elevated risk of developing asthma during lifetime.54 Epicutaneous sensitization to food allergens in atopic dermatitis is also a risk for food-related allergic reactions.72,79–83 In addition, patients with moderate to severe AD have substantial multidimensional burdens, including disease-related symptoms, itch, pain, sleep disturbance, depression, anxiety, and reduced health-related quality of life (HRQOL) both in children and adults.51–53
The Finnish National Anaphylaxis Registry documented 1,442 anaphylactic cases between 2000 and 2017.18 The most frequently reported provoking allergens were foods (56%), drugs (25%), and insect venoms (6%). Food triggered 76% of anaphylaxes in children, of which the six most frequent elicitors were cow’s milk, wheat, hen’s eggs, nuts, fruits, and fish. The amount of anaphylaxis due to nuts has significantly increased during the past 10 years. In adults, the most common causes of anaphylaxis were food (39%) and drugs (39%). Insect venom caused 38 (6%) anaphylaxes in children and 53 (7%) in adults. Anaphylaxis due to bee sting was rare (0% in children and 0.5% in adults).18 The number of allergic diseases, and the history of food allergy, atopic dermatitis and asthma increase the risk of self-reported anaphylaxis in Finnish adults.84 The incidence of allergic reactions leading to hospitalizations between 1999 and 2011 increased in Finland.47 During 1996–2013, three were 56 adult deaths in Finland due to anaphylaxis. At the same time, no children died from anaphylaxis.48 The number of anaphylaxis-related deaths among the Finnish population is between 1 to 7 annually, and the incidence of deaths varies from 0.19 to 1.28 per million person-years.35,48,85–87
The prevalence of allergic rhinitis (AR) is about 20% in the Western word.38,88,89 In Finland the most common allergens are pollens from birch family trees and grass as well as animal dander. AR often co-occurs with asthma and allergic conjunctivitis (AC) and is a global health problem causing a major burden and disability worldwide.38,50,88,90
Asthma is among the three most common chronic diseases in Finland that is reimbursed by the Finnish Social Security Institution (KELA).91 There are approximately 13,500 new asthma reimbursements granted for asthma annually, and the incidence has stayed almost constant for the last 10 years.91 The prevalence of asthma and asthma like symptoms is approximately 6–10% among adults, and 11% in children.16,92 The incidence of doctor-diagnosed asthma in children and adolescents is 3–6%.60,61 Risk factors of AR and/or asthma include sensitization to inhalant allergens and occupational allergens/irritants, tobacco smoking, other irritants, as well as genetic factors.88 The high number of allergic multimorbidities (AR, AC, AD) increase the risk of adult-onset asthma.90,93,94
Allergen sensitization and allergy tests
An organic substance contains numerous protein antigen molecules (also called allergen components) and has variable ability to cause sensitization by inducing allergen-specific IgE antibodies (Figure 2). There are also molecules that do not necessarily cause sensitization but can still cause allergic symptoms if previous contact with a related (cross-reactive) allergen has caused sensitization.
The clinical relevance of an allergen molecule varies according to the allergen source and protein family which it belongs to. Patients who are sensitized to labile cross-reactive molecules usually experience only mild, local symptoms, whereas stable allergen components are more likely to cause anaphylaxis. As an example, peanut contain several allergen molecules, of which the stable storage proteins have a higher capability to cause anaphylaxis than the labile, birch pollen-related, cross-reactive proteins (Fig. 2A). Cross-reactivity means that an antibody directed against one specific allergen can also recognize and bind to another allergen, even when it is from another source. (Fig. 2B).
Traditional allergy tests (skin prick and specific serum IgE tests) use whole allergen extracts that contain numerous molecules from the allergen source.95 They are suitable for testing inhaled allergens, for example. The use of single allergenic molecules, instead of extracts, has introduced a new area of high-resolution molecular allergy diagnostics (i.e., component-resolved diagnostics) and improved our understanding of sensitisation profiles and cross-reactivity between allergen sources. Allergen molecule-based component specific IgE tests are needed to evaluate patient´s anaphylaxis risk caused by foods, hymenoptera venom and latex.96 In addition, it is recommended that food allergy should be confirmed by oral food challenges.72 Using inappropriate testing methods may lead to misdiagnosis or overdiagnosis of allergic conditions and will inevitably affect the quality of the patient’s life as well as overall health care costs. Despite active epidemiological research, there is still a lack of knowledge of allergenic molecule component-specific sensitization profiles, cross reactivity, and their association with atopic morbidity.
Diagnosis of asthma
Asthma is a heterogenous disease characterized by chronic airway inflammation and variable airflow limitation. The diagnosis of asthma is based on the clinical history and evidence of airway hyperresponsiveness. Bronchodilator reversibility should be documented by standardized lung functions tests, such as spirometry and impulse oscillometry. Bronchial provocation tests (e.g., exercise challenge, methacholine, histamine, eucapnic voluntary hyperventilation) increase the sensitivity of lung function tests. There are several potential sources of errors when lung function tests are performed. Poorly performed tests result in flawed diagnoses and increased costs.
Treatment of atopic diseases
The baseline treatments of AR and/or AC are antihistamines, cromoglycates, intranasal corticosteroids, and anti-inflammatory eye drops. The standard treatment of asthma depends on its severity and comorbidities and includes inhaled corticosteroids (ICS), short-acting beta-agonists (SABA), added by long-acting beta-agonists (LABA), long-acting anticholinergic (LAMA), antileukotrienes, and oral corticosteroids (OCS) if needed. Advanced therapy includes biologicals (e.g., anti-IgE, anti IL5/IL5R, anti IL4Rα) for Type 2 high inflammation.91,97
Allergen immunotherapy (AIT) is an effective treatment for aeroallergen (birch, timothy, dog, cat, and house dust mite) derived AR, AC, and asthma. Hymenoptera venom allergy is most effectively treated by AIT.98 There are no published comprehensive data on the use of AIT for inhalant allergens in Finland. From the sales data, it is estimated that currently there are roughly 10,000 patients on AIT therapy, including subcutaneous (SCIT) and sublingual (SLIT) immunotherapy. Although the use of AIT therapy has increased in Finland during the last 10 years, it is still markedly underutilized, and there is significant regional variation for the availability of AIT.
For AD, the treatment is based on efficient use of local anti-inflammatory creams, and in moderate-to-severe cases also biologicals.99,100 Food allergy is mostly treated by avoiding the allergen that produces moderate to severe symptoms. Desensitization therapy for food allergens may be used in special cases.101