Systemic Manifestations of Atopic Dermatitis: A Systematic Review
Main Article Content
Keywords
atopic dermatitis, eczema, systemic, comorbidities, atopic march,
Abstract
Background: Atopic dermatitis (AD) is known to be associated with other allergic diseases, which often develop later in life in a serial fashion. This progression is termed the “atopic march” and is considered the classical presentation of atopic disease. However, recent evidence suggests that this paradigm may not hold true for a significant portion of patients with these conditions. Not only is the timing of development likely more complex than previously believed, the comorbidities associated with AD are possibly more numerous and varied.
Methods: This two-step systematic review involved a targeted search of PubMed and EMBASE with an additional hand search of key journals. The terms “atopic dermatitis” and “atopic eczema” were searched in conjunction with multiple keywords representing the concept of systemic nature of disease. All titles and abstracts were subsequently screened for relevance to the research question.
Results: This review’s evidence supports an association between AD and other atopic diseases. However, it also suggests that the classical paradigm of the “atopic march” does not apply to all patients with atopic dermatitis. There appears to be a significant association between AD and multiple neuro-psychiatric comorbidities, particularly ASD and ADHD. Additional themes supported by lower-level evidence are increased risk of cardiovascular disease, decreased risk of type I diabetes, and increased risk of multiple malignancies in patients with AD.
Conclusion: There is likely a diversity of phenotypes for patterns of allergic disease. Both positive and negative associations identified in this systematic review suggest that AD is condition with varied systemic manifestations.
References
2. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. Journal of Allergy and Clinical Immunology. 2003 Dec 31;112(6):S118-27.
3. Belgrave DC, Granell R, Simpson A, Guiver J, Bishop C, Buchan I, Henderson AJ, Custovic A. Developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies. PLoS Med. 2014 Oct 21;11(10):e1001748.
4. Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, Amagai M, Luger TA, Deleuran M, Werfel T, Eyerich K, Stingl G. Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder. Journal of Investigative Dermatology. 2017 Jan 31;137(1):18-25.
5. Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
6. Illi S, von Mutius E, Lau S, Nickel R, Gruber C, Niggemann B, et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. The Journal of allergy and clinical immunology. 2004;113(5):925-31.
7. Barberio G, Pajno GB, Vita D, Caminiti L, Canonica GW, Passalacqua G. Does a 'reverse' atopic march exist? Allergy: European Journal of Allergy and Clinical Immunology. 2008;63(12):1630-2.
8. Decreased prevalence of atopic diseases in children with diabetes. The EURODIAB Substudy 2 Study Group. The Journal of pediatrics. 2000;137(4):470-4.
9. Olesen AB, Juul S, Birkebaek N, Thestrup-Pedersen K. Association between atopic dermatitis and insulin-dependent diabetes mellitus: a case-control study. Lancet (London, England). 2001;357(9270):1749-52.
10. Sekigawa I, Yoshiike T, Iida N, Hashimoto H, Ogawa H. Allergic disorders in systemic lupus erythematosus: Prevalence and family history. Lupus. 2002;11(7):426-9.
11. Sekigawa I, Yoshiike T, Iida N, Hashimoto H, Ogawa H. Allergic disorders in systemic lupus erythematosus: Prevalence and family history. Lupus. 2002;11(7):426-9.
12. Schmitt J, Schwarz K, Baurecht H, Hotze M, Folster-Holst R, Rodriguez E, et al. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. The Journal of allergy and clinical immunology. 2016;137(1):130-6.
13. Hjuler KF, Bottcher M, Vestergaard C, Deleuran M, Raaby L, Botker HE, et al. Increased Prevalence of Coronary Artery Disease in Severe Psoriasis and Severe Atopic Dermatitis. The American journal of medicine. 2015;128(12):1325-34.e2.
14. Andersen YM, Egeberg A, Gislason GH, Hansen PR, Skov L, Thyssen JP. Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. The Journal of allergy and clinical immunology. 2016;138(1):310-2.e3.
15. Chung SD, Keller JJ, Lin HC. Association of erectile dysfunction with atopic dermatitis: a population-based case-control study. The journal of sexual medicine. 2012;9(3):679-85.
16. Wei CC, Lin CL, Shen TC, Li TC, Chen AC. Atopic Dermatitis and Association of Risk for Henoch-Schonlein Purpura (IgA Vasculitis) and Renal Involvement Among Children: Results From a Population-Based Cohort Study in Taiwan. Medicine. 2016;95(3):e2586.
17. Caffarelli C, Cavagni G, Deriu FM, Zanotti P, Atherton DJ. Gastrointestinal symptoms in atopic eczema. Archives of disease in childhood. 1998;78(3):230-4.
18. Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, et al. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. The Journal of allergy and clinical immunology. 2013;132(3):601-7.e8.
19. Kimata H. Fatty liver in atopic dermatitis. Allergy. 2001 May 1;56(5):460.
20. Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, Pan TL, Bai YM. Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study. Journal of psychosomatic research. 2014 Oct 31;77(4):316-21.
21. Garg N, Silverberg JI. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014;112(6):525-32.
22. Garg N, Silverberg JI. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014;112(6):525-32.
23. Schmitt J, Apfelbacher C, Chen CM, Romanos M, Sausenthaler S, Koletzko S, et al. Infant-onset eczema in relation to mental health problems at age 10 years: results from a prospective birth cohort study (German Infant Nutrition Intervention plus). The Journal of allergy and clinical immunology. 2010;125(2):404-10.
24. Reuveni H, Chapnick G, Tal A, Tarasiuk A. Sleep fragmentation in children with atopic dermatitis. Archives of pediatrics & adolescent medicine. 1999;153(3):249-53.
25. Jensen AO, Svaerke C, Farkas DK, Olesen AB, Kragballe K, Sørensen HT. Atopic Dermatitis and Risk of Skin Cancer. American journal of clinical dermatology. 2012 Feb 1;13(1):29-36.
26. Arana A, Wentworth CE, Fernández‐Vidaurre C, Schlienger RG, Conde E, Arellano FM. Incidence of cancer in the general population and in patients with or without atopic dermatitis in the UK. British Journal of Dermatology. 2010 Nov 1;163(5):1036-43.
27. Arellano FM, Arana A, Wentworth CE, Fernández-Vidaurre C, Schlienger RG, Conde E. Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom. Journal of Allergy and Clinical Immunology. 2009 May 31;123(5):1111-6.
28. Hwang CY, Chen YJ, Lin MW, Chen TJ, Chu SY, Chen CC, Lee DD, Chang YT, Wang WJ, Liu HN. Cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in Taiwan. International journal of cancer. 2012 Mar 1;130(5):1160-7.
29. Deckert S, Kopkow C, Schmitt J. Nonallergic comorbidities of atopic eczema: an overview of systematic reviews. Allergy. 2014 Jan 1;69(1):37-45.
30. Linabery AM, Jurek AM, Duval S, Ross JA. The association between atopy and childhood/adolescent leukemia: a meta-analysis. American journal of epidemiology. 2010 Apr 1;171(7):749-64.
31. Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. Journal of Allergy and Clinical Immunology. 2014 Apr 30;133(4):1041-7.
32. Hayashida S, Furusho N, Uchi H, Miyazaki S, Eiraku K, Gondo C, Tsuji G, Hachisuka J, Fukagawa S, Kido M, Nakahara T. Are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis?. Journal of dermatological science. 2010 Dec 31;60(3):173-8.
33. Ibáñez MD, Valero AL, Montoro J, Jauregui I, Ferrer M, Dávila I, Bartra J, Cuvillo A, Mullol J, Sastre J. Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain. Pediatric Allergy and Immunology. 2013 Nov 1;24(7):678-84.
34. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: A US population–based study. Journal of Allergy and Clinical Immunology. 2013 Nov 30;132(5):1132-8.
35. Fukunaga N, Okada Y, Konishi Y, Murashita T, Koyama T. Pay attention to valvular disease in the presence of atopic dermatitis. Circulation Journal. 2013;77(7):1862-6.
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