8 November 2019

Mental health in children with allergic rhinitis

Allergies Clinical Mental Health Paediatrics

There is growing interest in the morbidity of allergic rhinitis.

In the past, little if any attention was paid to the sequalae of untreated disease and future risk of inflammatory airway conditions.

There is now an established body of evidence linking allergic rhinitis with poor outcomes, such as reduced quality of life and academic achievement. Furthermore, there is now evidence that treating allergic rhinitis improves these outcomes.1,2

The connection between allergic rhinitis with mental health disorders is not so firmly established. Lately, there has been more interest in exploring this association given the rise in prevalence of both disorders and considering the vast array of negative consequences associated with both pathologies.

The prevalence of allergic rhinitis, along with other allergic diseases, has continued to increase in developed countries for the past couple of decades. Australia and New Zealand have among the highest rates of allergic rhinitis worldwide.1,2 Approximately one in five Australians report being affected by “hay fever”. Approximately 10% of children under 14 in Australia are reported to have symptoms.

Allergic rhinitis is an inflammatory, IgE-mediated disease characterised by inflammation of the mucosal lining of the nose that occurs when a person inhales airborne allergens to which he or she is sensitised to, such as animal dander, dust mites, or pollen.

Allergic rhinitis is associated with other allergic and respiratory diseases such as allergic conjunctivitis, chronic rhinosinusitis, and asthma.2 Allergic rhinitis is classified as being either persistent or intermittent depending on the duration of the symptoms. This can then be further classified as either mild, moderate or severe. Symptoms are considered to be moderate or severe based on how they affect the person’s quality of life.

Moderate or severe symptoms may impact the sufferer’s sleep quality. They may also impair daily activities of sport and leisure and/or impair work or school activities.3  The economic impact of the disease was estimated to be $7.8 billion dollars in 2007, with $5.6 billion due to lost productivity.4 Allergic rhinitis is the most common chronic respiratory condition in Australia and the incidence is highest when people are at their most productive, during school years and early work life.2

Mental health complaints are the most common cause of presentation to a GP in Australia and it is predicted that the size of the problem will continue to increase. The Royal Australian College of General Practitioners released a report following a survey of 1,200 GPs in September, 2019 which found that that mental health complaints were the most common reasons to visit a GP in Australia.

The second most common cause for presentation was respiratory complaints.5 Adults and children with atopic diseases including asthma, allergic rhinitis and atopic dermatitis may experience physical or social impairments as well as an associated reduction in quality of life.6

A nationwide mental health in children survey conducted in Australia in 2013–2014 looked at the rate of seven disorder modules from the Diagnostic Interview Schedule for Children Version 4 (DISC-IV). These seven disorders were chosen based on prevalence and impact. A total of 6310 parents or carers of 4-17-year-olds were interviewed face-to-face and 2969 11-17-year-olds completed a tablet survey on their own.

The study found that mental health disorders were one of the most common conditions affecting children and adolescents with 13.9% of four to 17-year-olds having a mental health disorder in the past year.

The most common type of mental health disorder was attention deficit hyperactivity disorder (ADHD) followed by anxiety disorders as a group. In older adolescents and teens, self-reported depressive disorder was also a substantial. These disorders are associated with loss of productivity, poor concentration, school absenteeism and poor academic performance.7  A very similar outcome to a child suffering allergic disease described previously.

A brief look into history of research into the association between allergic disorders and psychological conditions reveals interesting patterns regarding the hypothesised aetiology of symptoms of allergic disease. The hypotheses tested in these early studies demonstrate the beliefs surrounding the link between psychological conditions and allergy prior to the development of current understanding of inflammatory pathways and allergic diseases.

Alexander, French and colleagues (1941) proposed an excessive unresolved dependence on the mother could precipitate an asthma attack in a child when separation was threatened. They hypothesised that a combination of sensitisation to allergens and the separation conflict produced the symptoms of asthma and treating either factor could bring relief.

The idea that asthma was a psychosomatic complaint was also explored by Sabbath and Luce (1952) Funkenstein (1950) and Igersheimer (1956). These researchers looked at the lack of asthma symptoms in patients during a psychotic episode as opposed to symptoms being present when they were considered well. Their questions as well as others of their time speculated on an interesting relationship between respiratory allergy symptoms and the connection to psychological wellbeing, in particular, where allergic symptoms are the psychosomatic results of specific psychological diseases.

Dekker and Groen (1951) and Wolf (1952) looked at the emotional precipitation of allergic symptoms in both asthma and allergic rhinitis and found they could exacerbate symptoms through emotional arousal.8

While the above theories make for an interesting read, they also give an insight into the limited understanding of pathophysiology of allergic diseases at that time. 

These studies lack scientific methodology, consistency and are mostly based on case studies. However, they do highlight the long-observed relationship between allergic responses and psychological states. Furthermore, with the current understanding of the association between physiological and psychological stress and atopic disease risk and exacerbation, these early clinicians were possibly not completely misguided.

Mechanisms linking psychological stress, personal experience, and emotional response with atopic disease are currently the subject of ongoing research. Hormones, neuropeptides and cytokines released when a person experiences stress are hypothesised to be involved in both immune and neurogenic inflammatory processes.

When a homoeostatic hormonal or immunological state is dysregulated by a chronically stressed state, the result may be expressed clinically in chronic disease. While IgE mediated diseases are being studied with respect to the above, so are many other chronic non–communicable diseases. Further research into this continues and much more is needed.9

More recent studies have established a link between allergic disease and the development of psychological disorders. 

A population-based cohort study in Taiwan, looked at the association between people with allergic diseases (asthma, allergic rhinitis, atopic dermatitis) and their risk of developing psychiatric disorders. This study utilised the Taiwan National Insurance (NHI) Program database to identify cases and matched controls. The NHI at start of the study was reported to represent 99% of the population.

This study had large numbers (46,647 allergic patients, and 139,941 in the non-allergic control group). The results showed a statistically significant risk of developing a psychiatric disorder compared to the controls (10.8% study subjects, 6.7% controls (p= <0.001)). The authors concluded that there was a 1.66-fold increased hazard risk of developing a psychiatric disorder if you had asthma, allergic rhinitis, and/or atopic dermatitis in Taiwan.

They also looked at individual allergic disease.

They found atopic dermatitis alone and atopic dermatitis with allergic rhinitis was associated with a lower risk of psychiatric disorders, but all other groups were associated with a higher risk. This study has several limitations.  Specifically, not all relevant data is recorded in the NHI database.

Of particular concern, the study group numbers are not typical of allergic populations in other population-based studies.

In other studies, there is approximately 80% chance of having allergic rhinitis if you have asthma.3 In contrast, in this study there were 40,405 asthma patients and 1,809 had allergic rhinitis.10 This discrepancy suggests the allergic rhinitis group is vastly underrepresented which calls into question the reliability of the data collection techniques.3,10

A cross sectional survey on child health in Copenhagen was conducted in 2009. From that survey a selection of children with information pertaining to at least one atopic disease and one mental health problem were included in a subsequent study looking at a possible correlation and whether socioeconomic status had any impact.

The mental health problems were measured by a standardised questionnaire the Strengths and Difficulties Questionnaire.

The study found that children with symptoms of atopic dermatitis, asthma or allergic rhinitis, regardless of gender, age group and parent socioeconomic status, were more likely to have emotional, conduct and hyperactivity problems, compared with children without the atopic disease.

It was also found that children of lower socioeconomic status in general had more mental health issues than those in higher income families.  Associated atopic diseases added equally to the burden of mental health problems independent of carer income.

Unfortunately, a cross-sectional study will not prove causality, and while the number of children included was large (9215) this only represents a relatively modest proportion (47.9%) of those invited to participate. There is a risk of non-response bias when interpreting these results.11

Around the same time, a very similarly designed study was done in Palermo. This study looked for relationships between respiratory allergy and depressive or anxious mood in 10 to 13-year-old children.

Although this study also utilised a cross-sectional study design, the investigators employed a method of statistical analysis aimed at showing a causal relationship between the variables. The partial direct acyclic graph (P-DAG) is a tool to show how the probability of one variable is going to change due to the observation of other variables regardless of sample size.

The graph is designed to demonstrate associations and causal relationships. They identified a high prevalence of depressive (13.6%) and anxious (16%) states in respondents with allergic disease.

The authors concluded that allergic rhinitis had a causal role in depressive mood and depressive mood in anxiety. Asthma was also linked to a depressive mood, but through associated allergic rhinitis and not directly.

A strong effect of female gender on anxiety was noted, and this effect even higher in females with depressive mood. The high rates may be a reflection of the self-reporting.

While this is an innovative way to analyse the relationship between allergic disease and mental health, more research looking at other associated biological, psychological, environmental factors would allow for more robust results.12

Slattery et al also looked at the association between anxiety and depression and allergic diseases but attempted to demonstrate more specificity between the manifestation of mental health with respect to having either asthma, atopic dermatitis, or allergic rhinitis. They concluded general anxiety disorders were associated with asthma and allergic rhinitis but found no association with atopic dermatitis. Depressive symptoms were not associated with any of the three atopic disorders.13

A group in Cincinnati also looked at the association between atopic disorders and symptoms of internalising disorders, however they took a prospective, longitudinal approach.

Their cohort selected newborns who were at risk for allergic disease (one parent with skin prick testing proven allergy). They were followed up at either one, two, or three years, and four years of age and assessed for development of allergy. They brought the children back at age seven, and evaluated for onset of allergic disease as well as anxiety, behavioural and depressive disorders with the Behaviour Assessment System for Children, Second Edition (BASC-2).

Their results showed a three-fold increased odds of internalising disorder symptoms in children with early onset of allergic diseases.

The major limitation noted in this study was that the investigators selected children born with an increased risk of allergy, but they did not collect data on the parent’s history of mental health disorders. Hence, we do not know if these children were at an increased risk of internalising disorders courtesy of family history.

This group questioned whether biological mechanisms can be a factor in manifestation of allergic disease. The authors hypothesised a bidirectional link between allergic disorders and mental health disorders.14

The idea of a bidirectional link was initially explored a few years earlier in a systematic review and meta-analysis by Chida et al in 2008. These investigators found that psychological factors were involved in the development as well as prognosis of allergic disorders.

They suggest a reciprocal relationship between the two disorders may be mediated by behaviours and environmental pathways. For example, stress leading to poor diet, sleep disturbances, smoking and drinking, poor medication compliance all of which are known to exacerbate atopic disease. The reverse being uncontrolled symptoms leading to social impairment, medication costs, specialist costs, and frustration around time to diagnosis can all have an adverse impact on mental health. The effect of atopic disease on future mental health had a stronger association than the reverse in this analysis.15

Chavira et al looked at a group of children in the public care sector in California who were diagnosed with anxiety disorders and looked at the prevalence and impact of coexisting medical disorders. They looked at children aged 6-18 who had an anxiety disorder and a physical illness (73), children with an anxiety disorder without a physical illness (77) and children with a physical illness but no anxiety disorder (438).

The sample group were randomly selected from children in the public care sectors. Prevalence of anxiety disorders alone (8.7%) was similar to that of the general population in children (6-10%), however, physical illnesses among children with anxiety disorders were higher.

Rates of asthma and other allergic disease in the US is approximately 10% and 13% respectively, in this study the rate of comorbid asthma was 19% and 27.7% for any other chronic allergy.

Asthma and other chronic allergy were the most frequently reported medical comorbidities and all together 51% of children with an anxiety disorder reported any physical illness. This study was limited by geographical location as well as possible selection bias. These children were from a high-risk sample who were socioeconomically disadvantaged and may have experienced stressful situations and therefore not representative of the general community.16

Chang and his group in South Korea looked at the association between asthma, allergic rhinitis and atopic dermatitis and internalising and externalising disorders including Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD) in pre-schoolers. They found similar results to older children in previous studies. Internalising behavioural problem scores were significantly higher in those diagnosed with allergic rhinitis. A major limitation in a population this age is reporting of symptoms, there is heavy reliance on parents and carers to report what is generally not able to be communicated clearly by the patient.17

The relationship between allergic diseases and ADD/ADHD is controversial. The evidence thus far has been conflicting.

A recent systematic review and meta-analysis by Miyazaki et al looked at the evidence for connection between allergic diseases and ADHD. They decided to exclude studies whereby behaviour assessments were made according to the allergic severity and not by ADHD clinical diagnoses. Unfortunately, only five studies from and original 250 were deemed eligible. While the relative odds were slightly higher for allergic rhinitis, the evidence was of very low quality with a high risk of bias.18 

Another study looking at ADHD and oppositional defiance disorder (ODD) in children with allergic diseases observed the strongest links were active atopic dermatitis with inattentive ADHD and active allergic rhinitis with combined ADHD.

The odds for ADHD-related behavioural disorders increased when children had both allergic diseases and depression, anxiety, or poor sleep. Once again showing a positive correlation but no causality.19

In conclusion, while there is a growing body of evidence, causality remains an unanswered question. What is known is the morbidity of both allergic diseases and mental health disorders is substantial. Ongoing research in this area is necessary and a must. Our aim should be able to identify those at risk and manage effectively to prevent long -erm harm and complications.

Dr Jessica Tattersall is a general allergist and medical rhinologist  based in Sydney. She has a special interest in allergic and inflammatory diseases of the airway

References:

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