Skip to main content
Log in

Association Between Atopic Dermatitis and Autism Spectrum Disorders: A Systematic Review

  • Systematic Review
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Background

Atopic dermatitis (AD) is an allergic disorder caused by both immunological dysregulation and epidermal barrier defect. Several studies have investigated the association between AD and mental health disorders. Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social communication and restricted, stereotyped interests and behaviors. The concurrent increased prevalence of AD and ASD in the last decades has led many scientists to investigate the relationship between the two diseases.

Objective

The aim of this systematic review was to examine the association between AD and ASD.

Methods

A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and ScienceDirect were searched up to March 2015 for all reports examining the association between ASD and AD. Descriptive statistics of the studies are reported.

Results

The review included 18 studies assessing the association between ASD and AD. Of these studies, two focused on ASD in relation to AD alone, 14 discussed ASD in relation to both AD and other atopic disorders, and two evaluated AD in parents of children with ASD. Most of these studies found a positive association between the two disorders, although there were some studies going in the opposite direction. The entity of the association is somewhat inconsistent among the different studies given that the frequencies of AD in ASD compared with a control group ranged from 7 to 64.2 %. In addition, odds ratios (ORs) or hazard ratios (HRs) gave different results as three studies found a weak association with an OR below 2 and a nonsignificant p value, and three other studies found a moderate or strong association with an OR ranging from 1.52 to 7.17 and a significant p value. When all atopic disorders were considered when evaluating the risk of ASD, the association was strong with an HR of 3.4 or an OR of 1.24 and p < 0.001.

Conclusions

Overall, the results of this systematic review seem to reveal an association between ASD and AD, suggesting that subjects with ASD have an increased risk of presenting with AD compared with typically developing controls, and vice versa. This association is supported by clinical/epidemiological aspects, shared genetic background and common immunological and autoimmune processes. However, the variability in study population and design, and the presence of other risk factors acting as confounding factors, sometimes contribute to inconsistent results. Further studies are needed to clarify the underlying pathophysiologic mechanism explaining the association between ASD and AD and to explore the causal association between the two conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.

    Google Scholar 

  2. Matson JL, Kozlowski AM. Autistic regression. Res Autism Spectr Disord. 2010;4:340–5.

    Article  Google Scholar 

  3. Zappella M. Autistic regression with and without EEG abnormalities followed by favourable outcome. Brain Dev. 2010;32(9):739–45.

    Article  PubMed  Google Scholar 

  4. Levy SE, Mandell DS, Schultz RT. Autism. Lancet. 2009;374(9701):1627–38.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Weiss LA, Arking DE, Daly MJ, Chakravarti A. A genome-wide linkage and association scan reveals novel loci for autism. Nature. 2009;461(7265):802–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol. 2010;23(2):103–10.

    Article  PubMed  Google Scholar 

  7. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders: autism and developmental disabilities monitoring network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012;61(3):1–19.

  8. Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012. Natl Health Stat Report. 2013;65:1–11.

    PubMed  Google Scholar 

  9. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, ISAAC Phase Three Study Group, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross sectional surveys. Lancet. 2006;368:733–43.

    Article  PubMed  Google Scholar 

  10. Schernhammer ES, Vutuc C, Waldhör T, Haidinger G. Time trends of the prevalence of asthma and allergic disease in Austrian children. Pediatr Allergy Immunol. 2008;19:125–31.

    Article  CAS  PubMed  Google Scholar 

  11. Garg N, Silverberg JI. Epidemiology of childhood atopic dermatitis. Clin Dermatol. 2015;33(3):281–8.

    Article  PubMed  Google Scholar 

  12. Jackson KD, Howie LD, Akinbami LJ. Trends in allergic conditions among children: United States, 1997–2011. NCHS Data Brief. 2013;121:1–8.

    PubMed  Google Scholar 

  13. Hansen TE, Evjenth B, Holt J. Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among schoolchildren: three surveys during the period 1985–2008. Acta Paediatr. 2013;102:47–52.

    Article  PubMed  Google Scholar 

  14. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–94.

    Article  CAS  PubMed  Google Scholar 

  15. Plotz SG, Ring J. What’s new in atopic eczema? Expert Opin Emerg Drugs. 2010;15:249–67.

    Article  PubMed  Google Scholar 

  16. Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol. 2010;105(2):99–106.

    Article  CAS  PubMed  Google Scholar 

  17. Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res. 2011;3(2):67–73.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Darlenski R, Kazandjieva J, Hristakieva E, Fluhr JW. Atopic dermatitis as a systemic disease. Clin Dermatol. 2014;32(3):409–13.

    Article  PubMed  Google Scholar 

  19. Morar N, Willis-Owen SA, Moffatt MF, Cookson WO. The genetics of atopic dermatitis. J Allergy Clin Immunol. 2006;118:24–34.

    Article  CAS  PubMed  Google Scholar 

  20. Simpson EL. Atopic dermatitis: a review of topical treatment options. Curr Med Res Opin. 2010;26(3):633–40.

    Article  CAS  PubMed  Google Scholar 

  21. Schram ME, Tedja AM, Spijker R, Bos JD, Williams HC, Spuls PI. Is there a rural/urban gradient in the prevalence of eczema? A systematic review. Br J Dermatol. 2010;162(5):964–73.

    Article  CAS  PubMed  Google Scholar 

  22. Bieber T, de la Salle H, Wollenberg A, Hakimi J, Chizzonite R, Ring J, et al. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med. 1992;175:1285–90.

    Article  CAS  PubMed  Google Scholar 

  23. Bieber T, Novak N. Pathogenesis of atopic dermatitis: new developments. Curr Allergy Asthma Rep. 2009;9:291–4.

    Article  CAS  PubMed  Google Scholar 

  24. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss of function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38:441–6.

    Article  CAS  PubMed  Google Scholar 

  25. Simpson EL. Comorbidity in atopic dermatitis. Curr Dermatol Rep. 2012;1(1):29–38.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Brunsting LA. Atopic dermatitis (disseminated neurodermatitis) of young adults. Analysis of precipitating factors in one hundred and one cases and report of ten cases with associated juvenile cataract. Arch Dermatol Syphilol. 1936;34(6):935–57.

    Article  Google Scholar 

  27. Chamlin SL. The psychosocial burden of childhood atopic dermatitis. Dermatol Ther. 2006;19(2):104–7.

    Article  PubMed  Google Scholar 

  28. Faulstich ME, Williamson DA, Duchmann EG, Conerly SL, Brantley PJ. Psychophysiological analysis of atopic dermatitis. J Psychosom Res. 1985;29(4):415–7.

    Article  CAS  PubMed  Google Scholar 

  29. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. Br Med J. 2009;339:b2700.

    Article  Google Scholar 

  30. Yaghmaie P, Koudelka CW, Simpson EL. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol. 2013;131(2):428–33.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Adil H, Siegfried E, Armbrecht E. The impact of severe atopic dermatitis: analysis of comorbidities. J Am Acad Dermatol. 2014;70(5):AB66.

  32. Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, et al. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006;172(1–2):198–205.

    Article  CAS  PubMed  Google Scholar 

  33. Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr. 2005;146(5):605–10.

    Article  CAS  PubMed  Google Scholar 

  34. Jyonouchi H, Geng L, Cushing-Ruby A, Quraishi H. Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study. J Neuroinflamm. 2008;5:52.

    Article  CAS  Google Scholar 

  35. Mostafa GA, Hamza RT, El-Shahawi HH. Allergic manifestations in autistic children: relation to disease severity. J Pediatr Neurol. 2008;6(2):115–23.

    Google Scholar 

  36. Mostafa GA, El-Sherif D, Hamza RT, Shehab A. Hyperserotonemia in Egyptian autistic children: relation to allergic manifestations. J Pediatr Neurol. 2008;6(3):227–36.

    Google Scholar 

  37. Mostafa GA, Al-Ayadhi LY. The possible relationship between allergic manifestations and elevated serum levels of brain specific auto-antibodies in autistic children. J Neuroimmunol. 2013;261(1–2):77–81.

    Article  CAS  PubMed  Google Scholar 

  38. Magalhães ES, Pinto-Mariz F, Bastos-Pinto S, Pontes AT, Prado EA, deAzevedo LC. Immune allergic response in Asperger syndrome. J Neuroimmunol. 2009;216(1–2):108–12.

    Article  PubMed  CAS  Google Scholar 

  39. Zerbo O, Leong A, Barcellos L, Bernal P, Fireman B, Croen LA. Immune mediated conditions in autism spectrum disorders. Brain Behav Immun. 2015;46:232–6.

    Article  CAS  PubMed  Google Scholar 

  40. Garg N, Silverberg JI. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. Ann Allergy Asthma Immunol. 2014;112(6):525–32.

    Article  PubMed  Google Scholar 

  41. Schieve LA, Gonzalez V, Boulet SL, Visser SN, Rice CE, Van Naarden Braun K, et al. Concurrent medical conditions and health care use and needs among children with learning and behavioral developmental disabilities, National Health Interview Survey, 2006–2010. Res Dev Disabil. 2012;33(2):467–76.

    Article  PubMed  Google Scholar 

  42. Shibata A, Hitomi Y, Kambayashi Y, Hibino Y, Yamazaki M, Mitoma J, et al. Epidemiological study on the involvements of environmental factors and allergy in child mental health using the Autism Screening Questionnaire. Res Autism Spectr Disord. 2013;7(1):132–40.

    Article  Google Scholar 

  43. Chen MH, Su T, Chen Y, Hsu J, Huang K, Chang W, et al. Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: a nationwide population-based study. Res Autism Spectr Disord. 2013;7(2):205–12.

    Article  Google Scholar 

  44. Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, et al. Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study. J Child Psychol Psychiatry. 2013;54(5):545–51.

    Article  PubMed  Google Scholar 

  45. Lin TY, Lin PY, Su TP, Chen YS, Hsu JW, Huang KL, et al. Autistic spectrum disorder, attention deficit hyperactivity disorder, and allergy: is there a link? A nationwide study. Res Autism Spectr Disord. 2014;8(10):1333–8.

    Article  Google Scholar 

  46. Croen LA, Grether JK, Yoshida CK, Odouli R, Van de Water J. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case-control study. Arch Pediatr Adolesc Med. 2005;159(2):151–7.

    PubMed  Google Scholar 

  47. Larsson M, Weiss B, Janson S, Sundell J, Bornehag CG. Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6–8 years of age. Neurotoxicology. 2009;30(5):822–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Burgess NK, Sweeten TL, McMahon WM, Fujinami RS. Hyperserotoninemia and altered immunity in autism. J Autism Dev Disord. 2006;36(5):697–704.

    Article  PubMed  Google Scholar 

  49. Laughter D, Istvan J, Tofte S, Hanifin J. The prevalence of atopic dermatitis in Oregon schoolchildren. J Am Acad Dermatol. 2000;43(4):649–55.

    Article  CAS  PubMed  Google Scholar 

  50. Krämer U, Schäfer T, Behrendt H, Ring J. The influence of cultural and educational factors on the validity of symptom and diagnosis questions for atopic eczema. Br J Dermatol. 1998;139(6):1040–6.

    Article  PubMed  Google Scholar 

  51. Wing L. Sex ratios in early childhood autism and related conditions. Psychiatry Res. 1981;5(2):129–37.

    Article  CAS  PubMed  Google Scholar 

  52. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Williams JG, Higgins JP, Brayne CE. Systematic review of prevalence studies of autism spectrum disorders. Arch Dis Child. 2006;91(1):8–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Lauritsen MB, Pedersen CB, Mortensen PB. Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry. 2005;46(9):963–71.

    Article  PubMed  Google Scholar 

  55. Burke HL, Yeo RA, Vranes L, Garry PJ, Goodwin JS. Handedness, developmental disorders, and in vivo and in vitro measurements of immune responses. Dev Neuropsychol. 1988;4(2):103–15.

    Article  Google Scholar 

  56. Flannery KA, Liederman J. Is there really a syndrome involving the co-occurrence of neurodevelopmental disorder talent, non-right handedness and immune disorder among children? Cortex. 1995;31(3):503–15.

    Article  CAS  PubMed  Google Scholar 

  57. Geschwind N, Galaburda AM. Cerebral lateralization: biological mechanisms, associations, and pathology. I: a hypothesis and a program for research. Arch Neurol. 1985;42(5):428–59.

    Article  CAS  PubMed  Google Scholar 

  58. Geschwind N, Galaburda AM. Cerebral lateralization: biological mechanisms, associations, and pathology. II: a hypothesis and a program for research. Arch Neurol. 1985;42(5):521–52.

    Article  CAS  PubMed  Google Scholar 

  59. Geschwind N, Galaburda AM. Cerebral lateralization: biological mechanisms, associations, and pathology. III: a hypothesis and a program for research. Arch Neurol. 1985;42(5):634–54.

    Article  CAS  PubMed  Google Scholar 

  60. Barnes KC. An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Allergy Clin Immunol. 2010;125(1):16–29.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Freitag CM. The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry. 2007;12(1):2–22.

    Article  CAS  PubMed  Google Scholar 

  62. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46(8):881–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Edfors-Lubs ML. Allergy in 7000 twin pairs. Acta Allergol. 1971;26(4):249–85.

    Article  CAS  PubMed  Google Scholar 

  64. Schultz Larsen FV, Holm NV. Atopic dermatitis in a population based twin series. Concordance rates and heritability estimation. Acta Derm Venereol Suppl (Stockh). 1985;114:159.

  65. Larsen FS, Holm NV, Henningsen K. Atopic dermatitis. A genetic-epidemiologic study in a population based twin sample. J Am Acad Dermatol. 1986;15(5 Pt 1):487–494.

  66. Strachan DP, Wong HJ, Spector TD. Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins. J Allergy Clin Immunol. 2001;108(6):901–7.

    Article  CAS  PubMed  Google Scholar 

  67. van Beijsterveldt CE, Boomsma DI. Genetics of parentally reported asthma, eczema and rhinitis in 5-yr-old twins. Eur Respir J. 2007;29(3):516–21.

    Article  PubMed  Google Scholar 

  68. McGirt LY, Beck LA. Innate immune defects in atopic dermatitis. J Allergy Clin Immunol. 2006;118:202–8.

    Article  CAS  PubMed  Google Scholar 

  69. Persico AM, Napolioni V. Autism genetics. Behav Brain Res. 2013;251:95–112.

    Article  PubMed  Google Scholar 

  70. Tamauchi H, Terashima M, Ito M, Maruyama H, Ikewaki N, Inoue M, et al. Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response. Int Immunol. 2004;16:179–87.

    Article  CAS  PubMed  Google Scholar 

  71. Moriguchi T, Takako N, Hamada M, Maeda A, Fujioka Y, Kuroha T, et al. Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation. Development. 2006;133:3871–81.

    Article  CAS  PubMed  Google Scholar 

  72. Tsarovina K, Pattyn A, Stubbusch J, Muller F, van der Wees J, Schneider C, et al. Essential role of Gata transcription factors in sympathetic neuron development. Development. 2004;131:4775–86.

    Article  CAS  PubMed  Google Scholar 

  73. Trottier G, Srivastava L, Walker CD. Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. J Psychiatry Neurosci. 1999;24:103–15.

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Rout UK, Clausen P. Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders. Neurosci Res. 2009;64(2):162–9.

    Article  CAS  PubMed  Google Scholar 

  75. Connors SL, Crowell DE, Eberhart CG, Copeland J, Newschaffer CJ, Spence SJ, et al. Beta2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins. J Child Neurol. 2005;20(11):876–84.

    Article  PubMed  Google Scholar 

  76. Cheslack-Postava K, Fallin MD, Avramopoulos D, Connors SL, Zimmerman AW, Eberhart CG, et al. Beta2-adrenergic receptor gene variants and risk for autism in the AGRE cohort. Mol Psychiatry. 2007;12(3):283–91.

    CAS  PubMed  Google Scholar 

  77. Roguedas AM, Audrezet MP, Scotet V, Dupré-Goetghebeur D, Ferec C, Misery L. Intrinsic atopic dermatitis is associated with a beta-2 adrenergic receptor polymorphism. Acta Derm Venereol. 2006;86(5):447–8.

    Article  PubMed  Google Scholar 

  78. Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci. 1996;93(15):7849–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Renner P, Roger T, Calandra T. Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases. Clin Infect Dis. 2005;41(7):S513–9.

    Article  CAS  PubMed  Google Scholar 

  80. Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, et al. Role for macrophage migration inhibitory factor in asthma. Proc Natl Acad Sci. 2005;102(40):14410–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Yasuda C, Enomoto A, Ishiwatari S, Mori N, Kagoyama K, Matsunaga K, et al. Macrophage migration inhibitory factor (MIF) in the stratum corneum: a marker of the local severity of atopic dermatitis. Exp Dermatol. 2014;23(10):764–6.

    Article  PubMed  Google Scholar 

  82. Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22:123–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Tonacci A, Borghini A, Mercuri A, Pioggia G, Andreassi MG. Brain-derived neurotrophic factor (Val66Met) polymorphism and olfactory ability in young adults. J Biomed Sci. 2013;20:57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Halepoto DM, Bashir S, Al-Ayadhi L. Possible role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder: current status. J Coll Physicians Surg Pak. 2014;24(4):274–8.

    PubMed  Google Scholar 

  85. Chen CP, Lin SP, Chern SR, Tsai FJ, Wu PC, Lee CC, et al. A de novo 7.9 Mb deletion in 22q13.2 → qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet. 2010;53(5):329–32.

    Article  PubMed  Google Scholar 

  86. Redecker P, Bockmann J, Böckers TM. Expression of postsynaptic density proteins of the ProSAP/Shank family in the thymus. Histochem Cell Biol. 2006;126:679–85.

    Article  CAS  PubMed  Google Scholar 

  87. Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81:1289–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Sehra S, Holbreich M, Kaplan MH, Barbé Tuana FM, Mousdicas N, Travers JB. Clinical correlations of recent developments in the pathogenesis of atopic dermatitis. An Bras Dermatol. 2008;83(1):57–73.

    Article  Google Scholar 

  89. Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology. 2000;45(1):1–6.

    Article  Google Scholar 

  90. Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, Li X. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 2011;8:52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Singh VK, Warren RP, Odell JD, Cole P. Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. Clin Immunol Immunopathol. 1991;61(3):448–55.

    Article  CAS  PubMed  Google Scholar 

  92. Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamine induced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol. 2009;161(5):1072–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Yarlagadda A, Alfson E, Clayton AH. The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (Edgmont). 2009;6(11):18–22.

    Google Scholar 

  94. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, et al. Mast cell activation and autism. Biochim Biophys Acta. 2012;1822(1):34–41.

    Article  CAS  PubMed  Google Scholar 

  96. Theoharides TC. Is a subtype of autism an allergy of the brain? Clin Ther. 2013;35(5):584–91.

    Article  CAS  PubMed  Google Scholar 

  97. McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133:872–83.

    Article  PubMed  Google Scholar 

  98. Grubišić V, Kennedy AJ, Sweatt JD, Parpura V. Pitt-Hopkins mouse model has altered particular gastrointestinal transits in vivo. Autism Res. 2015. doi:10.1002/aur.1467.

    PubMed  Google Scholar 

  99. Muszer M, Noszczyńska M, Kasperkiewicz K, Skurnik M. Human microbiome: when a friend becomes an enemy. Arch Immunol Ther Exp (Warsz). 2015;63(4):287–98.

    Article  CAS  Google Scholar 

  100. Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, et al. Staphylococcus epidermidisesp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature. 2010;465:346–9.

    Article  CAS  PubMed  Google Scholar 

  101. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012;22(5):850–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Stecher B, Chaffron S, Käppeli R, Hapfelmeier S, Freedrich S, Weber TC, et al. Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog. 2010;6(1):e1000711.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  103. Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, et al. Food allergy and infantile autism. Panminerva Med. 1995;37:137–41.

    CAS  PubMed  Google Scholar 

  104. Chambers ES, Suwannasaen D, Mann EH, Urry Z, Richards DF, Lertmemongkolchai G, et al. 1α,25-dihydroxyvitamin D3 in combination with transforming growth factor-β increases the frequency of Foxp3+ regulatory T cells through preferential expansion and usage of interleukin-2. Immunology. 2014;143(1):52–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Pioggia G, Tonacci A, Tartarisco G, Billeci L, Muratori F, Ruta L, et al. Autism and lack of D3 vitamin: a systematic review. Res Autism Spectr Disord. 2014;8(12):1685–98.

    Article  Google Scholar 

  106. Jia F, Wang B, Shan L, Xu Z, Staal WG, Du L. Core symptoms of autism improved after vitamin D supplementation. Pediatrics. 2015;135(1):e196–8.

    Article  PubMed  Google Scholar 

  107. Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013;34:47–64.

    Article  CAS  PubMed  Google Scholar 

  108. Hayes CE, Nashold FE, Spach KM, Pedersen LB. The immunological functions of the vitamin D endocrine system. Cell Mol Biol. 2003;49:277–300.

    CAS  PubMed  Google Scholar 

  109. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln LR, Burrell A, et al. A ChIP-seq-defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20:1352–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Ehlayel MS, Bener A, Sabbah A. Is high prevalence of vitamin D deficiency evidence for asthma and allergy risks? Eur Ann Allergy Clin Immunol. 2011;43:81–8.

    CAS  PubMed  Google Scholar 

  111. Benson AA, Toh JA, Vernon N, Jariwala SP. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Allergy. 2012;67:296–301.

    Article  CAS  PubMed  Google Scholar 

  112. Kanda N, Hau CS, Tada Y, Sato S, Watanabe S. Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M. Allergy. 2012;67(6):804–12.

    Article  CAS  PubMed  Google Scholar 

  113. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.

    Article  CAS  PubMed  Google Scholar 

  114. Kokkonen J, Niinimaki A. Increased incidence of autoimmune disorders as a late complication in children with early onset dermatitis and/or milk allergy. J Autoimmun. 2004;22(4):341–4.

    Article  CAS  PubMed  Google Scholar 

  115. Mittermann I, Aichberger KJ, Bunder R, Mothes N, Renz H, Valenta R. Autoimmunity and atopic dermatitis. Curr Opin Allergy Clin Immunol. 2004;4(5):367–71.

    Article  CAS  PubMed  Google Scholar 

  116. Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004;3(7–8):557–62.

    Article  CAS  PubMed  Google Scholar 

  117. Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol. 2005;71:317–41.

    Article  CAS  PubMed  Google Scholar 

  118. Singh VK, Warren RP, Odell JD, Warren WL, Cole P. Antibodies to myelin basic protein in children with autistic behavior. Brain Behav Immun. 1993;7(1):97–103.

    Article  CAS  PubMed  Google Scholar 

  119. Singh VK, Warren R, Averett R, Ghaziuddin M. Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol. 1997;17(1):88–90.

    Article  CAS  PubMed  Google Scholar 

  120. Singh VK, Rivas WH. Prevalence of serum antibodies to caudate nucleus in autistic children. Neurosci Lett. 2004;355(1–2):53–6.

    Article  CAS  PubMed  Google Scholar 

  121. Singh VK, Lin SX, Yang VC. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol. 1998;89(1):105–8.

    Article  CAS  PubMed  Google Scholar 

  122. Mostafa GA, El-Sayed ZA, El-Aziz MM, El-Sayed MF. Serum anti-myelin-associated glycoprotein antibodies in Egyptian autistic children. J Child Neurol. 2008;23(12):1413–8.

    Article  PubMed  Google Scholar 

  123. Mostafa GA, Al-Ayadhi LY. The possible link between the elevated serum levels of neurokinin A and anti-ribosomal P protein antibodies in children with autism. J Neuroinflamm. 2011;8:180.

    Article  CAS  Google Scholar 

  124. Mostafa GA, Al-Ayadhi LY. Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflamm. 2011;8:39.

    Article  CAS  Google Scholar 

  125. Dochniak MJ. Autism spectrum disorders: exogenous protein insult. Med Hypotheses. 2007;69(3):545–9.

    Article  CAS  PubMed  Google Scholar 

  126. Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56(7):481–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  127. Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A [published erratum appears in J Neuroimmunol 2002;130(1–2):248]. J Neuroimmunol. 2002;129(1–2):168–77.

    Article  CAS  PubMed  Google Scholar 

  128. Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology. 2002;46(2):76–84.

    Article  CAS  PubMed  Google Scholar 

  129. Mutter J, Naumann J, Schneider R, Walach H, Haley B. Mercury and autism: accelerating evidence? Neuro Endocrinol Lett. 2005;26(5):439–46.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giovanni Pioggia.

Ethics declarations

Funding

No funding was received for the preparation of this review.

Conflicts of interest

Drs. Lucia Billeci, Alessandro Tonacci, Gennaro Tartarisco, Liliana Ruta, Giovanni Pioggia and Sebastaino Gangemi have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Billeci, L., Tonacci, A., Tartarisco, G. et al. Association Between Atopic Dermatitis and Autism Spectrum Disorders: A Systematic Review. Am J Clin Dermatol 16, 371–388 (2015). https://doi.org/10.1007/s40257-015-0145-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-015-0145-5

Keywords

Navigation