Autism Spectrum Disorders and Allergy

Abstract and Introduction

Abstract

IgE-mediated allergic diseases (e.g., allergic rhinoconjunctivitis, atopic asthma and food allergy) are prevalent (up to 30%) in the general population and are increasing in developed countries. In infants and young children, non-IgE-mediated food allergy is also prevalent. In addition to easily recognized organ-specific symptoms, allergic diseases can cause neuropsychiatric symptoms, such as irritability and hyperactivity, in otherwise healthy individuals. This is also likely to occur in children with autism spectrum disorder (ASD). Moreover, the discomfort and pain associated with allergic diseases could aggravate behavioral symptoms in ASD children. Allergic conditions are easily treatable; however, ASD children may be underdiagnosed and/or undertreated for allergic and other common childhood diseases, in part due to their impaired communication skills. Practicing physicians should be aware of the potential impact of allergic diseases on behavioral symptoms and cognitive activity in ASD children. However, they also need to be aware that certain symptoms often attributed to 'allergy' by caregivers may not be immune mediated and should understand that behavioral symptoms can also be affected by many non-IgE-mediated causes.

Introduction

Autism spectrum disorder (ASD) is a complex developmental disorder characterized by impaired speech, social interactions and repetitive aberrant behaviors. The etiology of ASD is not well understood except for a small percentage of children (≤10–15%) with known genetic mutations.^[1] In the remainder of ASD children, ASD diagnosis is based on subjective behavioral symptoms, although recent studies have begun to elucidate the effects of genetic variations on ASD phenotypes.^[1,2] Behavioral symptoms in ASD children change as the child develops and can be affected by multiple factors, including underlying medical conditions. Therefore, current diagnostic criteria of ASD inevitably result in encompassing markedly heterogeneous patient populations.

Autism spectrum disorder children are known to suffer from multiple comorbidities, with gastrointestinal (GI) and sleep disorders being the most common.^[3,4] Certain behavioral symptoms are implicated with GI discomfort or pain.^[3] Parents of ASD children who experience GI symptoms often report an improvement in certain behaviors along with resolution of GI symptoms following implementation of dietary intervention measures, such as a casein-free/gluten-free diet. Such observations indicate that food allergy (FA) may impact the behavioral symptoms observed in some ASD children.

Allergic reactions can be divided into two categories: immediate and delayed-type reactions. Immediate allergic reactions are mediated by IgE antibody (Ab) bound to the high-affinity IgE receptor (FcɛRI) expressed on effector cells (mast cells and basophils).^[5] Thus, binding of allergen to cell surface IgE Ab rapidly activates effector cells, causing the release of inflammatory mediators within minutes upon allergen exposure.^[5,6] This results in an acute onset of 'allergic' symptoms. Allergic diseases (e.g., allergic rhinitis [AR], allergic conjunctivitis, IgE-mediated FA and atopic asthma) are common in developed countries. The prevalence of atopy (allergic diseases) is 25–30% in the general population and is rising,^[7,8] along with the prevalence of nonatopic asthma.^[9] Non-IgE-mediated food allergy, in which allergic symptoms manifest hours after exposure to the offending food, is also common in young children. Delayed onset of symptoms in non-IgE-mediated food allergy makes it challenging to diagnose in all children, irrespective of ASD status.^[10]

Retrospective analysis of ASD children evaluated in our pediatric allergy/immunology clinic indicates that allergic diseases are prevalent in ASD children, with a frequency equivalent to that in the general population.^[10,11] Unfortunately, owing to their impaired expressive language, aberrant behaviors and lower tolerance to diagnostic measures compared with typically developing children, diagnosing allergic diseases may be more challenging in ASD children.^[12] It has been our experience that ASD children are generally underdiagnosed and undertreated for allergic diseases as well as other nonallergic diseases that are common in children.

In our experience, parents of ASD children often present with concerns that their child may have an 'allergy' owing to the clinical features observed in their child. Very frequently, such 'allergy' symptoms are not associated with IgE-mediated or non-IgE-mediated immune reactions. It is very easy for practicing physicians to be overwhelmed when dealing with such ASD children and parents. Moreover, it needs to be emphasized that the behavioral changes observed in ASD children can be the result of many causes, and differentiating the effects of comorbidities on behavioral symptoms is rather challenging, as shown in attention deficit/hyperactivity disorder (ADHD) children.^[13,14] We stress that allergic disorders are only one of the things to consider if underlying medical conditions are suspected. Moreover, even if allergic disorders are associated with behavioral changes, the effects of allergic diseases can be quite variable in each individual due to the influence of various environmental and genetic factors.^[15–18]

In this review, mechanisms of IgE- and non-IgE-mediated allergic/immune reactions will be summarized first, since these conditions are often confused by practicing general pediatrians and parents. Second, owing to the limited amount of literature involving the ASD population, the effects of both 'allergic' and 'nonallergic' common childhood diseases on behavioral symptoms will be discussed in both typically growing and ASD children. Lastly, the author will discuss 'what is allergy' and 'what is not allergy', a frequent concern expressed by parents of ASD children in our clinic.

This article will hopefully alert readers to the crucial role that practicing physicians play in caring for ASD children, as well as the importance of timely diagnosis and treatment of underlying allergic/nonallergic conditions that are easily treatable. This is important not only for the improvement of the general wellbeing of ASD children, but also because it may help to attenuate their behavioral symptoms by relieving pain and discomfort caused by underlying medical conditions. In turn, this may ultimately facilitate their cognitive development.

Cite this: Autism Spectrum Disorders and Allergy: Observation from a Pediatric Allergy/immunology Clinic - Medscape - May 01, 2010.

Table 1. IgE-mediated and non IgE-mediated conditions seen in autism spectrum disorder children evaluated in the allergy/immunology clinic.
Condition	Diagnosis
Respiratory
IgE-mediated	Allergic conjunctivitis Allergic rhinitis Atopic asthma
Non-IgE mediated	Nonallergic rhinitis Non-atopic asthma Recurrent or chronic rhinosinusitis^† Gastroesophageal reflux disease Recurrent otitis media Adenoid hypertrophy
Gastrointestinal
IgE-mediated	IgE-mediated food allergy
Non-IgE-mediated	Non-IgE-mediated food allergy (food protein-induced enterocolitis syndrome) Celiac disease
Overlapping conditions^‡	Eosinophilic esophagitis Eosinophilic gastritis Eosinophilic enterocolitis
Skin
IgE-mediated	Extrinsic eczema (often associated with IgE-mediated food allergy)
Non-IgE-mediated	Intrinsic eczema

^†Chronic rhinosinusitis can also be associated with antibody deficiency syndrome, including common variable immunodeficiency and specific polysaccharide deficiency.
^‡Eosinophilic esophagitis and other eosinophilic syndromes may be more frequently evaluated in the pediatric gastroenterology clinic due to the requirement for endoscopic examination for diagnosis, and are not discussed in detail in this review.

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