Allergy of chronic origin, especially in young children, manifests symptoms (of varying degrees of severity) from various organs/systems and is multifactorial in nature [
27]. Multicentre cohort studies conducted in the population of young children showed strong coexistence between the response to more than 2 allergens and multiple morbidities, which concerned the co-occurrence of bronchial asthma, allergic rhinitis, eczema and allergic conjunctivitis [
27,
28]. An association between multiple morbidities and multiple allergies was also observed in adults [
15]. Our study involved both children and adults. In both these groups, an association between multiple morbidities and multiple allergies was found.
Multimorbidity is strongly associated with AR or A and, to a lesser extent, with AD. This paper offers novel findings and shows also association with food allergy and urticaria. Moreover, the paper brings other novel findings. Asthma or AD as single diseases are not associated with sensitization. Allergic rhinitis is associated with polysensitization but more so for SPT ≥ 3 mm. Multimorbidity is associated with polysensitization for SPT ≥ 3 and ≥ 6 mm. Cat is the allergen most strongly associated with multimorbidity.
Strengths and limitations
The study used canonical epidemiologic methods with validated methods for the diagnosis of allergic diseases. Moreover, the diagnosis was made by trained physicians and incorrect diagnoses are unlikely.
Diagnosis of polysensitization in the study was based on a SPT (8 groups of allergens) or sIgE assay (4 antibodies).
Only three allergic diseases (A, AR, AD) were included in the multimorbidity analysis because (i) this is the classical approach to allergic multimorbidity and (ii) we wanted to assess the impact of other allergic diseases in multimorbidity. Consideration of other allergic diseases in multimorbidity (e.g. food allergy) might have led to different conclusions.
Among the subjects with diagnosed AR, 14.5% (15.9% for AR alone) had a negative SPT. These diagnoses were based on clinical history. These cases require further analysis.
Due to the multicentre character the study was representative for individual age groups in each of the analysed 9 centres, however, it was not representative at the country level.
Interpretation of the findings
A, AR and AD were clearly associated with allergic multimorbidity. Also food allergy and urticaria increased the risk of multimorbidity. The role of venom allergy is more complex since the multivariable analysis showed no association, but according to a two-variable analysis it increased the risk. There was no association with drug allergy.
It is important to characterise multimorbidity across the life cycle. Although monosensitization and single allergic diseases are more common in infants, multimorbidity and polysensitization are found in preschool children [
29‐
34]. The present study shows that multimorbidity is more common in children but also exists in adults, confirming the study of Siroux et al. [
15].
Therefore it is essential to attempt to determine factors influencing the development of allergic multimorbidity. Ciprandi indicated that polysensitization co-occurs with multimorbidity [
34]. Usually, polysensitization is more common than monosensitization, which was also demonstrated in this study (Table
1). Multimorbidity is also usually associated with a more severe course of AR and A. If it co-occurs with AD in adults, its clinical picture is usually characterised by severe, chronic dermatitis and respiratory tract inflammation [
34,
35].
In the present study, the risk of multimorbidity was significantly associated with polysensitization. Multimorbidity was rare in case of negative SPTs, more frequent in subjects with one positive SPT reaction and very frequent in those with 2 or more positive SPT reactions to common inhalant allergens. Both SPT and slgE data were analysed, since according to epidemiologic studies, they show considerable overlap, but they do not have the same value for the interpretation of the allergic risk [
36]. In cases of strongly positive reactions in SPT the significant association is present for at least 4 allergens.
Interestingly, A or AD alone were not associated with polysensitization (Fig.
4 and Additional file
1: Table 4). Polysensitization was associated with multimorbidity for SPT size of ≥ 3 or ≥ 6 mm. For AR, association with polysensitization was only shown for SPT ≥ 3 mm. These data suggest that A or AD alone, are different phenotypes in comparison to multimorbid A or AD. The data related to the size of the SPT reaction are compelling and may suggest differences depending on the size of the SPT. More studies are needed to understand this finding.
Moreover, attention should be paid to the significance of A in cases of multimorbidity. A was not the most common disease entity occurring in cases of multimorbidity, but if it was diagnosed in a patient, the probability of multimorbidity was significantly higher. The present results refer both to the group of patients diagnosed with allergic diseases and to the group of individuals without diagnosed allergies. This kind of analysis was conducted because both positive SPT reactions and the presence of slgE in serum might occur in people without allergy or, conversely, allergic symptoms might be present in patients with negative SPTs as suggested by topical allergy, e.g. Rh without antibodies in blood serum [
37,
38]. This observation confirms the conclusion of Bousquet et al.: “Rhinitis is usually associated with mono- or polysensitization, whereas A is more often associated with polysensitization and multimorbidities” [
30].
The present study was not focused on asymptomatic patients. However, it has to be noted that this phenomenon should be taken into account in further analysis and might be relevant in determining the significance of specific disease entities in the development of multimorbidity and polysensitization.
Not only polysensitization plays an important role in multimorbidity; the species of allergens are also important. Sensitization to cat or house dust mites (HDM) was more strongly associated with multimorbidity than to pollens or moulds. Although cat and HDM are perennial allergens, hazel and grasses are not. However, in the Polish climate these two allergens (together with birch and alder, which exhibit strong cross-reactivity with hazel) have a long pollen season from the end of January to April. These data suggest that long-acting allergens may play an important role in multimorbidity because of prolonged time of exposure.
Age plays some role in multimorbidity. The prevalence of multimorbidity was more common in children and adolescents than in subjects over 20 years of age.