Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: A nationwide population-based study

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Abstract

Previous clinical and genetic studies have suggested autism spectrum disorders (ASDs) is associated with immunological abnormalities involving cytokines, immunoglobulins, inflammation, and cellular immunity, but epidemiological reports are still limited. Patients with ASDs were identified in the National Health Insurance Database from 1996 to 2010, and compared with age and gender-matched controls (1:4) in an investigation of the association between ASDs and allergic/autoimmune diseases. A total of 1596 patients with ASDs were identified, and were found to have a significantly higher prevalence of allergic and autoimmune diseases than the control group. Patients with ASDs had increased risks of asthma (OR = 1.74, 95%CI = 1.51–1.99), allergic rhinitis (OR = 1.70, 95%CI = 1.51–1.91), atopic dermatitis (OR = 1.52, 95%CI = 1.30–1.78), urticaria (OR = 1.38, 95%CI = 1.12–1.69) and type 1 diabetes (OR = 4.00, 95%CI = 1.00–16.00), and a trend toward increasing comorbidity with Crohn's disease (OR = 1.46, 95%CI = 0.90–2.35). Our results support the association between ASDs and allergic diseases, and autoimmune comorbidities (type 1 diabetes and Crohn's disease). Further basic study is required to elucidate the possible underlying mechanisms and roles of allergy immunity and autoimmunity in the etiology of ASDs.

Highlights

► Previous clinical studies have shown immunological abnormalities in patients with ASDs, but the large scale epidemiological reports are still limited. ► Patients with ASDs had a higher prevalence and risk of allergic diseases than the control group. ► Our study validated the possible association of ASDs with type 1 diabetes and Crohn's disease.

Section snippets

Background

Autism spectrum disorders (ASDs) are complex neurodevelopment disorders that begin in childhood. Individuals with ASDs manifest qualitative impairments in social cognition, deficient verbal and non-verbal communication, restricted interests, and stereotyped/repetitive behaviors, ranging in severity from patients with profound deficits to individuals that are highly functioning (Rapin, 1997, Rapin, 2002). The prevalence of ASDs has increased gradually, from 4 to 60–100/10,000 over the last

Data source

The National Health Insurance (NHI) program was implemented in Taiwan in 1995. Taiwan's NHI has covered 96.9% of all 23,000,000 residents of Taiwan since 2001. The completeness and accuracy of the NHI claims database has been audited by the Department of Health and the Bureau of NHI. The database provides demographic and medical information on insured residents, including age, gender, prescription drugs, prescription date, and the prescription and diagnosis using the International

Demographic characteristics of the ASDs study group and control group

Of the 1,000,000-person sample population identified between January 1, 1996 and December 31, 2010, 1274 males and 324 females were identified as having ASDs. Allergic diseases were prevalent in patients with ASDs. Compared with the control group, patients with ASDs had a significantly increased prevalence of allergic comorbidities, including asthma (23.3% vs. 15.3%, p < 0.001), AR (38.0% vs. 27.0%, p < 0.001), AD (17.8% vs. 13.0%, p < 0.001), and urticaria (8.4% vs. 6.3%, p = 002). In contrast to

Discussion

The ASDs patients in our study had a higher prevalence of allergic diseases than the control group, which was compatible with the findings in previous clinical observational studies and supported studies suggesting a possible shared etiology between ASDs and allergic diseases. In addition, we validated the possible association of ASDs with type 1 diabetes and Crohn's diseases (Afzal and Minor, 2002, Freeman et al., 2005), despite the low comorbid prevalence rates.

Limitations

Some limitations of this study need to be mentioned. First, the prevalence of ASDs, allergic, and autoimmune diseases may be underestimated because only those individuals who sought for medical help were identified. However, the patients with ASDs included in our study were given a diagnosis by board-certified psychiatrists using psychiatric interviews and clinical judgments, and the diagnoses were more reliable than those that are self-reported. Second, previous studies showed that a familial

Conclusion

In our study, with the largest case number reported thus far, the results supported the significant association between ASDs and allergic diseases, including asthma, AR, AD, and urticaria. The link between ASDs and various autoimmune diseases is characterized by mixed findings in previous studies, although patients with ASDs seem to have increased vulnerability to type 1 diabetes and Crohn's disease. Further study is required to elucidate the possible underlying mechanisms and roles of allergic

Conflict of interest

There is no conflict of interest.

Acknowledgements

The study was supported by grant from Taipei Veterans General Hospital (V101D-001-1).

We thanks Dr MHC and Dr YMB, who designed the study, wrote the protocol and manuscripts, Dr YMB, Dr TPS, Dr YSC, Dr JWH, and Dr KLH, who assisted with the preparation and proof-reading of the manuscript, and Dr YMB, Dr TJC, and Ms WHC provided the advices on statistical analysis.

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