This site is intended for healthcare professionals
Atopic Dermatitis Learning Zone

Atopic Dermatitis overview

Read time: 140 mins
Last updated:27th Jul 2021
Published:27th Jul 2021

Are you aware of the recent updates on atopic dermatitis? Read below to:

  • Engage with epidemiological images for atopic dermatitis across the globe
  • Learn more about treatment options and the evidence behind them
  • Find key detail relating to the presentation of atopic dermatitis and burden of the disease

Atopic dermatitis epidemiology

Prevalence and incidence of atopic dermatitis

Atopic dermatitis, or atopic eczema, is the most common chronic skin condition and is characterised by acute episodes of eczematous, pruritic lesions over dry skin. It typically starts in early childhood and is widely reported to affect 15–20% of children and 1–3% of adults1.

Since the 1970s, the incidence of atopic dermatitis has increased 2- to 3-fold in industrialised nations2.

While atopic dermatitis affects a substantial number of infants and adults, the severity can differ significantly between patients. Studies have shown reasonable heterogeneity in the relative levels of severity observed in patients. Analysis of the 2007–2008 National Survey of Children’s Health found that 67% of US children reported mild disease, 26% reported moderate disease and 7% reported severe disease3,4. However, a smaller study in the UK where disease severity was assessed by a dermatologist rather than patient self-report found that 84% of children had mild disease, 14% had moderate disease and just 2% had severe disease5.

AD_Fig1.2__6FF99733-0A1E-4BA9-B9FD52CCB66D1863.png

Figure 1: Atopic dermatitis disease severity classification (adapted from the National Institute for Health and Care Excellence6).

In children, 60% develop the disease in the first year of life and 90% within the first 5 years of life7. It is also believed to represent the first step of the ‘atopic march’ towards other allergic conditions later in life such as asthma or allergic rhinitis1. In a 3-year, double-blind study of 1,091 infants (3–18 months of age) with recent onset atopic dermatitis (≤3 months), development of one or more atopic comorbidities was observed in 37.0% of infants at the end of observation (mean 2.8 years)8.

AD_Fig2.1__0769CAAC-83B0-459F-B1823075DF62CB19.png

Figure 2: Incidence of different atopic diseases in childhood and adolescence (adapted from Barnetson & Rogers9).

In 70% of patients with childhood atopic dermatitis a spontaneous remission before adolescence is achieved1. Interestingly, however, a prospective cohort study of children with mild-to-moderate atopic dermatitis reported that 80% of patients with >5 years of follow-up continued to have symptoms or use medication. Furthermore, as patients aged, they sought healthcare support less frequently potentially influencing the common perception of the frequency with which atopic dermatitis resolves over time10. However, conflicting data and ongoing debate continues on this topic indicating that more research is needed to fully understand the long-term impact of atopic dermatitis11,12,13.

Although prevalence figures of 15–20% in children and 1–3% in adults are commonly quoted1, the American Academy of Dermatology guidelines suggest a childhood prevalence of up to 25%7.

Irrespective of the given prevalence, all these figures hide significant geographic and population variations. In the International Study of Asthma and Allergies in Childhood (ISAAC), a global study of 2 million children in 100 countries, prevalence in children aged 6–7 years was shown to be as low as 0.9% in parts of India and as high as 22.5% in Ecuador14.

AD_Fig3.png

Figure 3: Prevalence of atopic dermatitis in the last 12 months in phase 3 of the ISAAC study (adapted from Williams et al.15). Figures in parentheses represent the range of prevalence observed in different regions of the country where available.

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Atopic dermatitis pathophysiology

A complex range of factors influence the development and onset of atopic dermatitis, but what is the underlying mechanism that drives skin barrier dysfunction and inflammation? Discover how breakdown of the skin barrier can lead to allergen penetration and immune system activation.

Professor Seemal Desai describes current key hypotheses and research areas regarding the specific mechanisms involved in the pathophysiology of atopic dermatitis.

Pathogenesis

In the past, atopic dermatitis was thought to be primarily a consequence of immune dysfunction in susceptible children. However, recent advances point towards a complex pathophysiology with genetic, barrier function, immunity and environmental factors acting together and synergistically to drive barrier dysfunction, inflammation and disease progression25.

Two theories have been proposed for the pathophysiology of atopic dermatitis. The inside-out model proposes that an allergic response triggers inflammation that disrupts the skin barrier enabling further allergen and microbe exposure. The outside-in hypothesis, however, suggests that skin barrier dysfunction initiates the process of atopic dermatitis, with immune dysregulation occurring subsequently2.

AD_Fig6__6161B194-9BF2-49DD-9C124B0E6697BF07.png

Figure 6: Theories of atopic dermatitis pathogenesis (adapted from Sidbury & Barton32).

While some suggest that these models are unlikely to be exclusive and probably both play a role2, others suggest that skin barrier dysfunction, or the outside-in model, is the initiating step26.

Skin barrier dysfunction and atopic dermatitis

Within the epidermis, barrier proteins including filaggrin, transglutaminases, keratins and loricrin, and intercellular proteins cross-link into clusters to form an impermeable barrier26. This protects us from exogenous stressors and allergens, but also helps maintain internal fluid and electrolyte homeostasis. Disruption of the skin barrier enables the penetration of allergens that can trigger an immune response and may subsequently lead to the development of IgE-mediated allergies25. While skin barrier dysfunction is critical to the onset of atopic dermatitis, no individual cause has been identified. Instead, several factors contribute to the loss of skin barrier function.

AD_Fig7.png

Figure 7: Skin barrier dysfunction and atopic dermatitis (adapted from Peng & Novak33; Guttman-Yassky et al.34). Genetic, immunological, and mechanical factors lead to skin barrier dysfunction allowing activated antigen-presenting cells to encounter allergens, pathogens, and environmental factors. This results in promotion of a Th2-mediated immune response further damaging the skin barrier and inducing keratinocyte apoptosis. Increases in PDE4 also increase Th2 cytokine expression. Virulence factors released by colonising pathogens can also promote keratinocyte cell death and Th2-type inflammation further driving barrier dysfunction. DC, Dendritic cell; EO ceramides, ester-linked ω-hydroxy ceramides; FFAs, free fatty acids; IFN-γ, interferon-γ; IgE, immunoglobulin E; IL, interleukin; KLK7, kallikrein 7; LC, Langerhans cell; MCs, mast cells; MHC, major histocompatibility complex; PDE4, phosphodiesterase-4; TCR, T cell receptor; Th2, T helper 2 cells, TNFα, tumour necrosis factor α; TSLP, thymic stromal lymphopoietin; TWEAK, TNF-like weak inducer of apoptosis.

Epidermal barrier protein loss

While filaggrin plays an important role in the development of barrier protein clusters, it is also degraded upon exposure to low humidity into free amino acids, which are essential for maintaining skin pH and retaining water in the cornified layer35,36,37,38. Mutation of the filaggrin gene, FLG, is a well-known predisposing factor for atopic dermatitis development.

Filaggrin deficiency has been shown to cause paracellular skin barrier abnormalities that reduce inflammatory thresholds to irritants and haptens26. However, a significant number of patients with atopic dermatitis do not have a FLG mutation and approximately 40% of individuals with FLG-null alleles do not go on to develop atopic dermatitis39,26.

While FLG mutations clearly contribute to the development of atopic dermatitis in many people, it is not sufficient alone to generate the condition. Interestingly, FLG mutation is not the only means by which filaggrin levels are reduced.

A Th2-type inflammatory response is typically observed in acute atopic dermatitis and the Th2 cytokines IL-17, IL-22, IL-25 and IL-31 are capable of downregulating filaggrin expression. Indeed, while filaggrin mutations are observed in about one-third of Caucasian patients with atopic dermatitis, skin barrier impairment and reduced filaggrin expression are seen in most patients33.

Tight junctions, desmosomes and adherens junctions form adhesions between the cells of the epidermis to help create a physical, permeability barrier. The Th2 cytokines that downregulate filaggrin expression have also been shown to downregulate the proteins involved in tight junction formation resulting in increased transepidermal water loss, greater allergen and microbial penetration of the skin and reduced skin barrier cohesion40,41,26.

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Pruritis in atopic dermatitis

Problematic pruritus in atopic dermatitis

Itch is the most important clinical symptom in atopic dermatitis and has been shown to have a profound impact on the quality of life of both child and adult patients68,69. Importantly, chronic pruritus affects nearly everyone with atopic dermatitis with a point prevalence of 87–100%70,71.

"Without adequate therapy that addresses both the pathophysiological and emotional component of atopic dermatitis-related itch, problems with disease management and adherence to therapy amass in children, putting these patients at increased risk for the long-term sequelae associated with paediatric atopic dermatitis"68.

What are the underlying mechanisms of pruritis in atopic dermatitis?

Watch our expert Professor Martin Steinhoff introduce the signals and mediators involved in pruritis in atopic dermatitis:

Histamine, involved primarily in acute itch, is not alone in mediating pruritis. Having said this, because histamine is a well-known factor causing itch with urticaria caused by the degranulation of mast cells, antihistamine have been commonly used as a treatment. However, it has been found that because many other mechanisms are involved in the pathophysiology of the condition, antihistamines are not fully effective as a management strategy72.

Understanding itch in atopic dermatitis

It is apparent that histaminergic (as seen in urticaria) and non-histaminergic (such as atopic dermatitis) mechanisms can drive pruritus. While closely related, these two mechanisms appear to be independent of one another. In the skin, both mechanisms of pruritus have their own receptors and cutaneous nerve fibres, which continues into the central nervous system (CNS) where each has its own specialised tracts and neural structures73. Chronic pruritus, as seen in atopic dermatitis, is induced by the nonhistaminergic pathway and is likely to be a consequence of multiple factors related to skin barrier dysfunction.

Transepidermal water loss (TEWL) increases following skin barrier dysfunction due to a reduction in keratinocyte retention of water and increased loss of water from the surrounding epidermal environment74. Increased TEWL has been associated with itch intensity and has also been shown to increase the pH of the skin resulting in activation of serine proteases that promote further pruritus75,76. In fact, in atopic dermatitis, the receptor for proteases is typically upregulated and sensitised73.

Skin barrier dysfunction is also likely to allow increased entry of irritants and pruritogens, which further enhance the itch process. Upon entry to the skin, these compounds are capable of stimulating one of myriad receptors on the keratinocyte cell surface channels (such as PAR2, TRPV ion channels, IL-31 receptor, opioid receptors), promoting the release of pruritogenic molecules (including opioids, proteases, substance P, nerve growth factor, neutrotrophin 4, endocannabinoids). In addition, keratinocytes can release acetylcholine directly stimulating sensory nerves as well as lowering their threshold for stimuli activation73. Keratinocytes, therefore, can be stimulated by, and secrete, pruritic factors as well as communicate the itch sensation downstream.

Managing itch is multifactorial with a need to address the itch itself, but also contributing factors such as dry skin, inflammation, and scratch lesions. Basic therapy should be undertaken to address skin barrier dysfunction and includes the use of emollients, bath oils and avoiding any clinically relevant allergens. Beyond basic therapy, a range of topical and systemic treatment options are often used to help manage the itch associated with atopic dermatitis69.

Cytokines in itch

Cytokines are critical components in the pathogenesis of atopic dermatitis with some also playing an important role in atopic itch.

IL-2

Intradermal injection of IL-2 into patients with atopic dermatitis or healthy controls induced itching and erythema for 48–72 hours77. This link between IL-2 and itch has also been observed in patients receiving intravenous IL-2 as a cancer therapy with severe pruritus a recognised side effect78,79,80. Calcineurin promotes IL-2 synthesis and secretion80 and calcineurin inhibition with ciclosporin A was shown to reduce pruritus in patients with atopic dermatitis81.

IL-4 and IL-13

IL-4 and IL-13 help promote the Th2-driven immune response observed in patients with atopic dermatitis. Levels of both cytokines are increased in lesional skin82 and IL-13 levels are elevated in the serum of patients with atopic dermatitis where they correlate with disease severity83. The role of IL-4 and IL-13 in pruritus has been confirmed using a monoclonal antibody that targets the action of both IL-4 and IL-13 (dupilumab), which reduced pruritus severity by over 50% during clinical trials84.

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Atopic dermatitis symptoms

Atopic dermatitis, also called atopic eczema or eczema, is an inflammatory, chronic or chronically relapsing skin disease with pruritus as the predominant dermatological symptom68,105,69.

The condition typically presents in infancy, with 60% of cases occurring within the first year, however, it can develop in older patients with approximately one third of adult cases developing in adulthood68,69. Over time, the clinical presentation of atopic dermatitis changes68.

AD_Fig14__AB45D7CF-E549-4558-A99CBDAA9D3B512B.png

Figure 8: Changes in the clinical presentation of atopic dermatitis over time (adapted from Blume-Peytavi et al.68)

Skin features that are commonly associated with atopic dermatitis include:

Table 2: Common skin features associated with atopic dermatitis (adapted from Avena-Woods et al.2)

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Burden of disease for atopic dermatitis

As a chronic, relapsing skin condition, atopic dermatitis has a significant impact on patients’ quality of life. However, given the age of most patients, and the fact that it can persist into adulthood, atopic dermatitis also places a heavy burden on patients’ family as well as society2.

The misery of living with atopic dermatitis cannot be overstated for it may have a profoundly negative effect on the HRQoL of children and their family unit in many cases.
Lewis-Jones, 2006.

In fact, skin and subcutaneous diseases were the fourth leading cause of nonfatal burden in 2013 Global Burden of Disease Study, with dermatitis (atopic, seborrheic and contact) having the largest burden of that group107. Furthermore, a study using the Children’s Life Quality Index (CLQI) among children (aged 5–16 years) with various chronic diseases found generalised eczema to be second to only cerebral palsy in impact on quality of life108.

Dr Amy Paller discusses the urgent unmet needs that remain for patients with atopic dermatitis


Symptoms and comorbidities in atopic dermatitis

Pruritus, or itch, is the predominant symptom associated with atopic dermatitis. In a US study of 304 patients with atopic dermatitis, 91% experienced itch daily71. The impact of persistent itch should not be underestimated as it has been shown to affect both physical and emotional/psychological quality of life (QoL) domains. Indeed, reducing itch was identified as the most important treatment goal in 36% of patients with atopic dermatitis109. Furthermore, the physical damage caused by repeated scratching can exacerbate skin barrier breakdown and promote establishment of chronic disease68.

What is the burden of atopic dermatitis for patients?

Watch Professor Steinhoff discuss the considerable burden that pruritis can add for patients living with atopic dermatitis.

More recently, skin pain has also been identified as an important symptom associated with the burden of atopic dermatitis. A prospective, questionnaire-based study of patients with atopic dermatitis aged 13 years and older (N=305) established that 42.7% of patients had experienced skin pain in the past week, with 13.8% reporting it to be severe or very severe. Importantly, patients with severe itch and pain had significantly worse QoL scores than patients with only one or neither symptom110.

Asthma and allergic rhinitis

With atopic dermatitis frequently representing the first step in a series of allergy-related conditions (atopic march), it is well established that patients with atopic dermatitis have an increased risk of developing asthma and allergic rhinitis. In children with severe atopic dermatitis, as many as 50% went on to develop asthma and 75% developed allergic rhinitis111 from 14.2% to 52.7% with an odds ratio of developing asthma of 2.14 compared to children without atopic dermatitis. However, this may be higher than the risk for the general population given many of the included studies were performed in the hospital setting112. Interestingly, an Australian longitudinal study showed that childhood atopic dermatitis increased the risk of persistent allergic asthma in adulthood, but not non-allergic asthma offering potential therapeutic insights for these patients113.

Rheumatoid arthritis and inflammatory bowel disease

Gene mapping studies in atopic dermatitis have identified a number of loci involved in immune function that have also been implicated in other immune-mediated inflammatory diseases114. A large retrospective cohort study identified 49,847 individuals (N = 655,815; prevalence of 7.6%) under the age of 40 years who had prevalent atopic dermatitis between 2005 and 2006. After adjusting for age and sex, patients with atopic dermatitis, compared with those without atopic dermatitis, had significantly increased risks of Crohn’s disease, ulcerative colitis and rheumatoid arthritis115.

AD_Fig8.1__6A1F6112-639C-44B2-8E18122F9AD7C3D4.png

Figure 9: Risks of inflammatory bowel disease and rheumatoid arthritis comorbidities in patients with atopic dermatitis (adapted from Schmitt et al.115).

While the cause of these associations remains to be confirmed, it has been established that chronic atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease all involve prominent Th1 and Th17 immune responses. It is tempting to speculate that sustained Th1/Th17 inflammation in patients with chronic atopic dermatitis leads to an increased risk of other chronic inflammatory conditions115.

Burden of childhood atopic dermatitis

Sleep disturbance is a significant problem for infants and has been associated with a range of daytime behavioural deficits116,117,118,119. Over 60% of children with atopic dermatitis experience disturbed sleep patterns with rates of up to 89% in children during exacerbations120,18,121. Furthermore, a U.S. population-based study found that children with atopic dermatitis had sleep disturbance at least 4 nights a week3.

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Diagnosing atopic dermatitis

Several classification criteria have been developed, but the Hanifin and Rajka criteria originally developed in 1980 remain the most widely used worldwide69.

Diagnosis of atopic dermatitis relies strongly on clinical presentation and is typically made through an extensive history and physical examination2.

The original criteria developed by Hanifin and Rajka are thorough, requiring 3 of 4 basic features (pruritus, typical morphology and distribution, chronic or chronically relapsing dermatitis, personal or family history of atopy) and at least 3 of 23 minor features to be met155. While comprehensive and validated, the extensive criteria make their application difficult in everyday clinical practice. Various revisions have been developed to aid using them in clinical practice including those developed by the UK Working Party who narrowed the criteria down to needing 1 mandatory and 5 major features to be met. These criteria have no requirement for laboratory testing and have been validated in various populations, however, they cannot be applied to very young children156,157,158,159.

To address this limitation of the UK Working Group version, and to make the criteria more streamlined, the American Academy of Dermatology Consensus Conference proposed a further revision (Table 4)7. This version of the criteria has not been validated, but they were deemed suitable for diagnosing atopic dermatitis in patients of all ages2.

Table 4: American Academy of Dermatology consensus conference revision of the Hanifin & Rajka diagnostic criteria for atopic dermatitis (adapted from Eichenfield et al.7).

Atopic_Derm_Table4_Diagnosis__A7FF84BD-B7DE-4088-82FDB7B29D780BFE.png

Watch Dr Amy Paller discuss how atopic dermatitis can affect patients and the impact this has on their lives

Biomarkers

At present, no laboratory biomarkers have been identified to aid with the diagnosis of atopic dermatitis. The elevation of total- or allergen specific IgE in serum or the use of skin tests to detect IgE-mediated sensitisation has been proposed. However, this feature is not present in all patients and has led to the terms ‘intrinsic’ (non-IgE-associated) and ‘extrinsic’ (IgE-associated) being used to describe these different forms of atopic dermatitis. However, controversy persists around the use of these terms and the practical applications of IgE detection in patients with atopic dermatitis69. Despite variation in IgE levels, it has been shown that intrinsic and extrinsic atopic dermatitis patient groups had similar underlying expression levels of Th2-related genes. This suggests that the underlying pathophysiology of their atopic dermatitis may be more similar than expected160.

Beyond diagnostic biomarkers, there is a general lack of biomarkers available to support patient stratification and management. In the past, treatment was typically nonspecific and consisted of topical and systemic immunosuppressants. However, many patients failed to respond to treatment leading to concerns among patients. With the advent of targeted biologic therapies in atopic dermatitis, identification of eligible patients who are likely to respond to therapy is now of increased need to reassure patients and avoid costly treatment failure161.

Numerous studies are currently ongoing looking at a variety of potential atopic dermatitis biomarkers. However, at present none have been shown to be reliable or sensitive enough to support regular clinical use2,69.

 

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

References

  1. Nutten S. Atopic dermatitis: Global epidemiology and risk factors. Ann Nutr Metab. 2015;66:8–16.
  2. Avena-Woods C. Overview of atopic dermatitis. Am J Manag Care. 2017;23(8):S115–S123.
  3. Silverberg JI, Simpson EL. Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 2013;24(5):476–486.
  4. Silverberg JI, Simpson EL. Associations of childhood eczema severity: A US population-based study. Dermatitis. 2014;25(3):107–114.
  5. Emerson RM, Williams HC, Allen BR. Severity distribution of atopic dermatitis in the community and its relationship to secondary referral. Br J Dermatol. 1998;139(1):73–76.
  6. National Institute for Health and Care Excellence (NICE). Atopic eczema in under 12s: diagnosis and management. Clinical Guideline [CG57]. 2007. https://www.nice.org.uk/guidance/cg57. Accessed 18 June 2020.
  7. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis Work Group. J Am Acad Dermatol. 2014;70(2):338–351.
  8. Schneider L, Hanifin J, Boguniewicz M, Eichenfield LF, Spergel JM, Dakovic R, et al. Study of the atopic march: Development of atopic comorbidities. Pediatr Dermatol. 2016;33(4):388–398.
  9. Barnetson RSC, Rogers M. Childhood atopic eczema. Br Med J. 2002;324(7350):1376–1379.
  10. Margolis JS, Abuabara K, Bilker W, Hoffstad O, Margolis DJ. Persistence of mild to moderate atopic dermatitis. JAMA Dermatology. 2014;150(6):593–600.
  11. Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): A systematic review and meta-analysis. J Am Acad Dermatol. 2016;75(4):681-687.e11.
  12. Margolis DJ, Mitra N. Heterogeneity of data included in meta-analysis on persistence of atopic dermatitis changes interpretation. J Am Acad Dermatol. 2017;76(5):e181.
  13. Silverberg JI, Simpson EL. Reply to: “Heterogeneity of data included in meta-analysis on persistence of atopic dermatitis alters interpretation”. J Am Acad Dermatol. 2017;76(5):e183–e184.
  14. Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI, Aït-Khaled N, et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009;124(6). doi:10.1016/j.jaci.2009.10.009.
  15. Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR. Is eczema really on the increase worldwide? J Allergy Clin Immunol. 2008;121(4). doi:10.1016/j.jaci.2007.11.004.
  16. Silverberg JI. Public Health Burden and Epidemiology of Atopic Dermatitis. Dermatol Clin. 2017;35(3):283–289.
  17. Harrop J, Chinn S, Verlato G, Olivieri M, Norbäck D, Wjst M, et al. Eczema, atopy and allergen exposure in adults: A population-based study. Clin Exp Allergy. 2007;37(4):526–535.
  18. Hanifin JM, Reed ML, Drake LA, Koo J, Lebwohl MG, Leung DYM, et al. A population-based survey of eczema prevalence in the United States. Dermatitis. 2007;18(2):82–91.
  19. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: A US population-based study. J Allergy Clin Immunol. 2013;132(5):1132–1138.
  20. Silverberg JI. Health care utilization, patient costs, and access to care in US adults with eczema: A population-based study. JAMA Dermatology. 2015;151(7):743–752.
  21. Barbarot S, Auziere S, Gadkari A, Girolomoni G, Puig L, Simpson EL, et al. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy Eur J Allergy Clin Immunol. 2018;73(6):1284–1293.
  22. Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups—Variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018;27(4):340–357.
  23. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: Data from the 2003 national survey of children’s health. J Invest Dermatol. 2011;131(1):67–73.
  24. Williams HC, Pembroke AC, Forsdyke H, Boodoo G, Hay RJ, Burney PGJ. London-born black caribbean children are at increased risk of atopic dermatitis. J Am Acad Dermatol. 1995;32(2 PART 1):212–217.
  25. McPherson T. Current understanding in pathogenesis of atopic dermatitis. Indian J Dermatol. 2016;61(6):649–655.
  26. Kim BE, Leung DYM. Significance of skin barrier dysfunction in atopic dermatitis. Allergy, Asthma Immunol Res. 2018;10(3):207–215.
  27. Cardona ID, Sang HC, Leung DYM. Role of bacterial superantigens in atopic dermatitis: Implications for future therapeutic strategies. Am J Clin Dermatol. 2006;7(5):273–279.
  28. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151–1160.
  29. Merriman JA, Mueller EA, Cahill MP, Beck LA, Paller AS, Hanifin JM, et al. Temporal and Racial Differences Associated with Atopic Dermatitis Staphylococcus aureus and Encoded Virulence Factors. mSphere. 2016;1(6). doi:10.1128/msphere.00295-16.
  30. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WHI, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134(4):818–823.
  31. Glatz M, Jo JH, Kennedy EA, Polley EC, Segre JA, Simpson EL, et al. Emollient use alters skin barrier and microbes in infants at risk for developing atopic dermatitis. PLoS One. 2018;13(2). doi:10.1371/journal.pone.0192443.
  32. Sidbury R, Barton M. Advances in understanding and managing atopic dermatitis. F1000Research. 2015;4:1–7.
  33. Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45(3):566–574.
  34. Guttman-Yassky E, Hanifin JM, Boguniewicz M, Wollenberg A, Bissonnette R, Purohit V, et al. The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition. Exp Dermatol. 2019;28(1):3–10.
  35. Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol. 1986;115(1):84–92.
  36. Denecker G, Hoste E, Gilbert B, Hochepied T, Ovaere P, Lippens S, et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol. 2007;9(6):666–674.
  37. Nicotera P, Melino G. Caspase-14 and epidermis maturation. Nat Cell Biol. 2007;9(6):621–622.
  38. Jang H, Matsuda A, Jung K, Karasawa K, Matsuda K, Oida K, et al. Skin pH Is the master switch of kallikrein 5-mediated skin barrier destruction in a murine atopic dermatitis model. J Invest Dermatol. 2016;136(1):127–135.
  39. O’Regan GM, Sandilands A, McLean WHI, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689–693.
  40. De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.e7.
  41. Gruber R, Börnchen C, Rose K, Daubmann A, Volksdorf T, Wladykowski E, et al. Diverse Regulation of Claudin-1 and Claudin-4 in Atopic Dermatitis. Am J Pathol. 2015;185(10):2777–2789.
  42. Elias PM, Hatano Y, Williams ML. Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms. J Allergy Clin Immunol. 2008;121(6):1337–1343.
  43. Ali SM, Yosipovitch G. Skin pH: From basic science to basic skin care. Acta Derm Venereol. 2013;93(3):261–267.
  44. Leung DYM. New insights into atopic dermatitis: Role of skin barrier and immune dysregulation. Allergol Int. 2013;62(2):151–161.
  45. Danso M, Boiten W, van Drongelen V, Gmelig Meijling K, Gooris G, El Ghalbzouri A, et al. Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci. 2017;88(1):57–66.
  46. Ito S, Ishikawa J, Naoe A, Yoshida H, Hachiya A, Fujimura T, et al. Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis. J Eur Acad Dermatology Venereol. 2017;31(1):135–141.
  47. Kim D, Lee NR, Park SY, Jun M, Lee K, Kim S, et al. As in Atopic Dermatitis, Nonlesional Skin in Allergic Contact Dermatitis Displays Abnormalities in Barrier Function and Ceramide Content. J Invest Dermatol. 2017;137(3):748–750.
  48. Li S, Villarreal M, Stewart S, Choi J, Ganguli-Indra G, Babineau DC, et al. Altered composition of epidermal lipids correlates with Staphylococcus aureus colonization status in atopic dermatitis. Br J Dermatol. 2017;177(4):e125–e127.
  49. Zimmermann M, Koreck A, Meyer N, Basinski T, Meiler F, Simone B, et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol. 2011;127(1). doi:10.1016/j.jaci.2010.11.005.
  50. Rebane A, Zimmermann M, Aab A, Baurecht H, Koreck A, Karelson M, et al. Mechanisms of IFN-γ-induced apoptosis of human skin keratinocytes in patients with atopic dermatitis. J Allergy Clin Immunol. 2012;129(5):1297–1306.
  51. Yoo J, Omori M, Gyarmati D, Zhou B, Aye T, Brewer A, et al. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med. 2005;202(4):541–549.
  52. Oyoshi MK, Larson RP, Ziegler SF, Geha RS. Mechanical injury polarizes skin dendritic cells to elicit a TH2 response by inducing cutaneous thymic stromal lymphopoietin expression. J Allergy Clin Immunol. 2010;126(5). doi:10.1016/j.jaci.2010.08.041.
  53. Novak N. An update on the role of human dendritic cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2012;129(4):879–886.
  54. Boguniewicz M, Leung DYM. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233–246.
  55. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483.
  56. Niebuhr M, Langnickel J, Draing C, Renz H, Kapp A, Werfel T. Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: Impact of the TLR-2 R753Q polymorphism. Allergy Eur J Allergy Clin Immunol. 2008;63(6):728–734.
  57. Niebuhr M, Lutat C, Sigel S, Werfel T. Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis. Allergy Eur J Allergy Clin Immunol. 2009;64(11):1580–1587.
  58. Kuo IH, Carpenter-Mendini A, Yoshida T, McGirt LY, Ivanov AI, Barnes KC, et al. Activation of epidermal toll-like receptor 2 enhances tight junction function: Implications for atopic dermatitis and skin barrier repair. J Invest Dermatol. 2013;133(4):988–998.
  59. Otsuka A, Kabashima K. Mast cells and basophils in cutaneous immune responses. Allergy Eur J Allergy Clin Immunol. 2015;70(2):131–140.
  60. Nakamura Y, Oscherwitz J, Cease KB, Chan SM, Muñoz-Planillo R, Hasegawa M, et al. Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature. 2013;503(7476):397–401.
  61. Kusari A, Han AM, Schairer D, Eichenfield LF. Atopic Dermatitis: New Developments. Dermatol Clin. 2019;37(1):11–20.
  62. Cabanillas B, Brehler AC, Novak N. Atopic dermatitis phenotypes and the need for personalized medicine. Current Opinion in Allergy and Clinical Immunology. 2017;17(4):309–315.
  63. Schafer PH, Truzzi F, Parton A, Wu L, Kosek J, Zhang LH, et al. Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28(7):753–763.
  64. Hanifin JM, Chan SC. Monocyte Phosphodiesterase Abnormalities and Dysregulation of Lymphoctye Function in Atopic Dermatitis. J Invest Dermatol. 1995;105(s1):84S-88S.
  65. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 Receptor. Annu Rev Immunol. 2001;19(1):683–765.
  66. Baghoomian W, Na CH, Simpson EL. New and Emerging Biologics for Atopic Dermatitis. Am J Clin Dermatol. 2020. doi:10.1007/s40257-020-00515-1.
  67. Szalus K, Trzeciak M, Nowicki RJ. Jak-stat inhibitors in atopic dermatitis from pathogenesis to clinical trials results. Microorganisms. 2020;8(11):1–14.
  68. Blume-Peytavi U, Metz M. Atopic dermatitis in children: management of pruritus. J Eur Acad Dermatology Venereol. 2012;26:2–8.
  69. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatology Venereol. 2018;32(5):657–682.
  70. Yosipovitch G, Goon ATJ, Wee J, Chan YH, Zucker I, Goh CL. Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus. Int J Dermatol. 2002;41(4):212–216.
  71. Dawn A, Papoiu ADP, Chan YH, Rapp SR, Rassette N, Yosipovitch G. Itch characteristics in atopic dermatitis: Results of a web-based questionnaire. Br J Dermatol. 2009;160(3):642–644.
  72. Umehara Y, Kiatsurayanon C, Trujillo-Paez JV, Chieosilapatham P, Peng G, Yue H, et al. Intractable Itch in Atopic Dermatitis: Causes and Treatments. Biomedicines. 2021;9(3):229.
  73. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out? Clin Rev Allergy Immunol. 2016;51(3):263–292.
  74. Lodén M. Effect of moisturizers on epidermal barrier function. Clin Dermatol. 2012;30(3):286–296.
  75. Ny A, Egelrud T. Epidermal Hyperproliferation and Decreased Skin Barrier Function in Mice Overexpressing Stratum Corneum Chymotryptic Enzyme. Acta Derm Venereol. 2004;84(1):18–22.
  76. Lee CH, Chuang HY, Shih CC, Jong SB, Chang CH, Yu HS. Transepidermal water loss, serum IgE and β-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis. Br J Dermatol. 2006;154(6):1100–1107.
  77. Wahlgren CF, Hägermark Ö, Linder MT, Scheynius A. Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects. Arch Dermatol Res. 1995;287(6):572–580.
  78. Gaspari AA, Lotze MT, Rosenberg SA, Stern JB, Katz SI. Dermatologic Changes Associated With Interleukin 2 Administration. JAMA J Am Med Assoc. 1987;258(12):1624–1629.
  79. Lee RE, Gaspari AA, Lotze MT, Chang AE, Rosenberg SA. Interleukin 2 and Psoriasis. Arch Dermatol. 1988;124(12):1811–1815.
  80. Kremer AE, Feramisco J, Reeh PW, Beuers U, Oude Elferink RPJ. Receptors, cells and circuits involved in pruritus of systemic disorders. Biochim Biophys Acta - Mol Basis Dis. 2014;1842(7):869–892.
  81. Wahlgren CF, Scheynius A, Hagermark O. Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol. 1990;70(4):323–329.
  82. Jeong CW, Ahnt KS, Rho NK, Park YD, Lee DY, Lee JH, et al. Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR. Clin Exp Allergy. 2003;33(12):1717–1724.
  83. Metwally SS, Mosaad YM, Abdel-Samee ER, El-Gayyar MA, Abdel-Aziz AM, El-Chennawi FA. IL-13 gene expression in patients with atopic dermatitis: relation to IgE level and to disease severity. Egypt J Immunol. 2004;11(2):171–177.
  84. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2014;371(2):130–139.
  85. Oldhoff JM, Darsow U, Werfel T, Katzer K, Wulf A, Laifaoui J, et al. Anti-IL-5 recombinant humanized monoclonal antibody (Mepolizumab) for the treatment of atopic dermatitis. Allergy Eur J Allergy Clin Immunol. 2005;60(5):693–696.
  86. Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: End of the drought? J Allergy Clin Immunol. 2017;140(3):633–643.
  87. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: A new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117(2):411–417.
  88. Raap U, Wichmann K, Bruder M, Ständer S, Wedi B, Kapp A, et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol. 2008;122(2):421–423.
  89. Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)-31 activates signal transducer and activator of transcription (STAT)-1, STAT-5 and extracellular signal-regulated kinase 1/2 and down-regulates IL-12p40 production in activated human macrophages. Allergy Eur J Allergy Clin Immunol. 2013;68(6):739–747.
  90. Hawro T, Saluja R, Weller K, Altrichter S, Metz M, Maurer M. Interleukin-31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge. Allergy Eur J Allergy Clin Immunol. 2014;69(1):113–117.
  91. Kroeger KM, Sullivan BM, Locksley RM. IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38α-dependent pathway. J Leukoc Biol. 2009;86(4):769–778.
  92. Rankin AL, Mumm JB, Murphy E, Turner S, Yu N, McClanahan TK, et al. IL-33 Induces IL-13–Dependent Cutaneous Fibrosis. J Immunol. 2010;184(3):1526–1535.
  93. Savinko T, Matikainen S, Saarialho-Kere U, Lehto M, Wang G, Lehtimäki S, et al. IL-33 and ST2 in atopic dermatitis: Expression profiles and modulation by triggering factors. J Invest Dermatol. 2012;132(5):1392–1400.
  94. Tamagawa-Mineoka R, Okuzawa Y, Masuda K, Katoh N. Increased serum levels of interleukin 33 in patients with atopic dermatitis. J Am Acad Dermatol. 2014;70(5):882–888.
  95. Petra AI, Tsilioni I, Taracanova A, Katsarou-Katsari A, Theoharides TC. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin e. Allergy Asthma Proc. 2018;39(2):153–160.
  96. Moniaga CS, Jeong SK, Egawa G, Nakajima S, Hara-Chikuma M, Jeon JE, et al. Protease activity enhances production of thymic stromal lymphopoietin and basophil accumulation in flaky tail mice. Am J Pathol. 2013;182(3):841–851.
  97. Wilson SR, Thé L, Batia LM, Beattie K, Katibah GE, McClain SP, et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell. 2013;155(2):285–295.
  98. Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. The Biology of Thymic Stromal Lymphopoietin (TSLP). Adv Pharmacol. 2013;66:129–155.
  99. Jariwala SP, Abrams E, Benson A, Fodeman J, Zheng T. The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis. Clin Exp Allergy. 2011;41(11):1515–1520.
  100. Rinaldi G. The Itch-Scratch Cycle: A Review of the Mechanisms. Dermatol Pract Concept. 2019;9(2):90–97.
  101. Johanek LM, Meyer RA, Hartke T, Hobelmann JG, Maine DN, LaMotte RH, et al. Psychophysical and physiological evidence for parallel afferent pathways mediating the sensation of itch. J Neurosci. 2007;27(28):7490–7497.
  102. Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M. Separate peripheral pathways for pruritus in man. J Neurophysiol. 2008;100(4):2062–2069.
  103. Alexander JOD. The physiology of itch. Parasitology Today. 1986;2(12):345–351.
  104. Zhao ZQ, Liu XY, Jeffry J, Karunarathne WKA, Li JL, Munanairi A, et al. Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling. Neuron. 2014;84(4):821–834.
  105. Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26–30.
  106. Silverberg JI, Vakharia PP, Chopra R, Sacotte R, Patel N, Immaneni S, et al. Phenotypical Differences of Childhood- and Adult-Onset Atopic Dermatitis. J Allergy Clin Immunol Pract. 2018;6(4):1306–1312.
  107. Karimkhani C, Dellavalle RP, Coffeng LE, Flohr C, Hay RJ, Langan SM, et al. Global skin disease morbidity and mortality an update from the global burden of disease study 2013. JAMA Dermatology. 2017;153(5):406–412.
  108. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155(1):145–151.
  109. Schmitt J, Csötönyi F, Bauer A, Meurer M. Determinants of treatment goals and satisfaction of patients with atopic eczema. JDDG - J Ger Soc Dermatology. 2008;6(6):458–465.
  110. Vakharia PP, Chopra R, Sacotte R, Patel KR, Singam V, Patel N, et al. Burden of skin pain in atopic dermatitis. Ann Allergy, Asthma Immunol. 2017;119(6):548-552.e3.
  111. Gustafsson D, Sjöberg O, Foucard T. Development of allergies and asthma in infants and young children with atopic dermatitis - A prospective follow-up to 7 years age. Allergy Eur J Allergy Clin Immunol. 2000;55(3):240–245.
  112. van der Hulst AE, Klip H, Brand PLP. Risk of developing asthma in young children with atopic eczema: A systematic review. J Allergy Clin Immunol. 2007;120(3):565–569.
  113. Martin PE, Matheson MC, Gurrin L, Burgess JA, Osborne N, Lowe AJ, et al. Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: A prospective cohort study over 4 decades. J Allergy Clin Immunol. 2011;127(6). doi:10.1016/j.jaci.2011.02.041.
  114. Ellinghaus D, Baurecht H, Esparza-Gordillo J, Rodríguez E, Matanovic A, Marenholz I, et al. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet. 2013;45(7):808–812.
  115. Schmitt J, Schwarz K, Baurecht H, Hotze M, Fölster-Holst R, Rodríguez 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. J Allergy Clin Immunol. 2016;137(1):130–136.
  116. Hart CN, Palermo TM, Rosen CL. Health-related quality of life among children presenting to a pediatric sleep disorders clinic. Behav Sleep Med. 2005;3(1):4–17.
  117. Hiscock H, Bayer J, Gold L, Hampton A, Ukoumunne OC, Wake M. Improving infant sleep and maternal mental health: A cluster randomised trial. Arch Dis Child. 2007;92(11):952–958.
  118. Gregory AM, Van Der Ende J, Willis TA, Verhulst FC. Parent-reported sleep problems during development and self-reported anxiety/depression, attention problems, and aggressive behavior later in life. Arch Pediatr Adolesc Med. 2008;162(4):330–335.
  119. Yokomaku A, Misao K, Omoto F, Yamagishi R, Tanaka K, Takada K, et al. A study of the association between sleep habits and problematic behaviors in preschool children. Chronobiol Int. 2008;25(4):549–564.
  120. Reid P, Lewis-Jones MS. Sleep difficulties and their management in preschoolers with atopic eczema. Clin Exp Dermatol. 1995;20(1):38–41.
  121. Wittkowski A, Richards HL, Griffiths CEM, Main CJ. Illness perception in individuals with atopic dermatitis. Psychol Heal Med. 2007;12(4):433–444.
  122. Camfferman D, Kennedy JD, Gold M, Martin AJ, Lushington K. Eczema and sleep and its relationship to daytime functioning in children. Sleep Med Rev. 2010;14(6):359–369.
  123. Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38(1):3–8.
  124. Romanos M, Gerlach M, Warnke A, Schmitt J. Association of attention-deficit/hyperactivity disorder and atopic eczema modified by sleep disturbance in a large population-based sample. J Epidemiol Community Health. 2010;64(3):269–273.
  125. Strom MA, Fishbein AB, Paller AS, Silverberg JI. Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults. Br J Dermatol. 2016;175(5):920–929.
  126. Johansson EK, Ballardini N, Kull I, Bergström A, Wahlgren CF. Association between preschool eczema and medication for attention-deficit/hyperactivity disorder in school age. Pediatr Allergy Immunol. 2017;28(1):44–50.
  127. Absolon CM, Cottrell D, Eldridge SM, Glover MT. Psychological disturbance in atopic eczema: the extent of the problem in school‐aged children. Br J Dermatol. 1997;137(2):241–245.
  128. Daud LR, Garralda ME, David TJ. Psychosocial adjustment in preschool children with atopic eczema. Arch Dis Child. 1993;69(6):670–676.
  129. Yaghmaie P, Koudelka CW, Simpson EL. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol. 2013;131(2):428–433.
  130. Halvorsen JA, Lien L, Dalgard F, Bjertness E, Stern RS. Suicidal ideation, mental health problems, and social function in adolescents with eczema: A population-based study. J Invest Dermatol. 2014;134(7):1847–1854.
  131. Chamlin SL, Frieden IJ, Williams ML, Chren MM. Effects of atopic dermatitis on young American children and their families. Pediatrics. 2004;114(3):607–611.
  132. Paller AS, Mcalister RO, Doyle JJ, Jackson A. Perceptions of physicians and pediatric patients about atopic dermatitis, its impact, and its treatment. Clin Pediatr (Phila). 2002;41(5):323–332.
  133. Ward S. The Effective Management of Atopic Dermatitis in School-Age Children. Nurs Times. 2004;100(32):55–56.
  134. Lee S-I, Kim J, Han Y, Ahn K. A proposal: Atopic Dermatitis Organizer (ADO) guideline for children. Asia Pac Allergy. 2011;1(2):53.
  135. Schmitt J, Chen CM, Apfelbacher C, Romanos M, Lehmann I, Herbarth O, et al. Infant eczema, infant sleeping problems, and mental health at 10 years of age: The prospective birth cohort study LISAplus. Allergy Eur J Allergy Clin Immunol. 2011;66(3):404–411.
  136. Chernyshov P V. Stigmatization and self-perception in children with atopic dermatitis. Clin Cosmet Investig Dermatol. 2016;9:159–166.
  137. Zuberbier T, Orlow SJ, Paller AS, Taïeb A, Allen R, Hernanz-Hermosa JM, et al. Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):226–232.
  138. Brenninkmeijer EEA, Legierse CM, Sillevis Smitt JH, Last BF, Grootenhuis MA, Bos JD. The course of life of patients with childhood atopic dermatitis. Pediatr Dermatol. 2009;26(1):14–22.
  139. Su JC, Kemp AS, Varigos GA, Nolan TM. Atopic eczema: Its impact on the family and financial cost. Arch Dis Child. 1997;76(2):159–162.
  140. Holm EA, Jemec GBE. Time spent on treatment of atopic dermatitis: A new method of measuring pediatric morbidity? Pediatr Dermatol. 2004;21(6):623–627.
  141. Jemec GB, Esmann S, Holm E, Tycho A, Jørgensen TM. Time spent on treatment (TSOT). An independent assessment of disease severity in atopic dermatitis. Acta Dermatovenerol Alp Pannonica Adriat. 2006;15(3):119–24.
  142. Lewis-Jones S. Quality of life and childhood atopic dermatitis: The misery of living with childhood eczema. Int J Clin Pract. 2006;60(8):984–992.
  143. Lawson V, Lewis-Jones MS, Finlay AY, Reid P, Owens RG. The family impact of childhood atopic dermatitis: The Dermatitis Family Impact questionnaire. Br J Dermatol. 1998;138(1):107–113.
  144. Chamlin SL, Mattson CL, Frieden IJ, Williams ML, Mancini AJ, Cella D, et al. The price of pruritus: Sleep disturbance and cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med. 2005;159(8):745–750.
  145. Moore K, David TJ, Murray CS, Child F, Arkwright PD. Effect of childhood eczema and asthma on parental sleep and well-being: A prospective comparative study. Br J Dermatol. 2006;154(3):514–518.
  146. Napolitano M, Megna M, Patruno C, Gisondi P, Ayala F, Balato N. Adult atopic dermatitis: a review. G Ital Dermatol Venereol. 2016;151(4):403–11.
  147. Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey. J Am Acad Dermatol. 2018;78(1):54-61.e1.
  148. Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: An analysis using the National Health and Wellness Survey. J Am Acad Dermatol. 2017;77(2):274-279.e3.
  149. Dalgard FJ, Gieler U, Tomas-Aragones L, Lien L, Poot F, Jemec GBE, et al. The Psychological Burden of Skin Diseases: A Cross-Sectional Multicenter Study among Dermatological Out-Patients in 13 European Countries. J Invest Dermatol. 2015;135(4):984–991.
  150. Dieris-Hirche J, Gieler U, Petrak F, Milch W, te Wildt B, Dieris B, et al. Suicidal ideation in adult patients with atopic dermatitis: A German cross-sectional study. Acta Derm Venereol. 2017;97(10):1189–1195.
  151. Nyrén M, Lindberg M, Stenberg B, Svensson M, Svensson Å, Meding B. Influence of childhood atopic dermatitis on future worklife. Scand J Work Environ Heal. 2005;31(6):474–478.
  152. Holm EA, Esmann S, Jemec GBE. The handicap caused by atopic dermatitis - Sick leave and job avoidance. J Eur Acad Dermatology Venereol. 2006;20(3):255–259.
  153. Drucker AM, Qureshi AA, Amand C, Villeneuve S, Gadkari A, Chao J, et al. Health Care Resource Utilization and Costs Among Adults with Atopic Dermatitis in the United States: A Claims-Based Analysis. J Allergy Clin Immunol Pract. 2018;6(4):1342–1348.
  154. Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, et al. The burden of skin diseases: 2004. A joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3):490–500.
  155. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;92:44–47.
  156. Williams HC, Burney PG, Hay RJ, Archer CB, Shipley MJ, Hunter JJ, et al. The U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol. 1994;131(3):383–396.
  157. Williams HC, Burney PG, Pembroke AC, Hay RJ. Validation of the U.K. Diagnostic Criteria for Atopic Dermatitis in a Population Setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party. Br J Dermatol. 1996;135(1):12–7.
  158. Gu H, Chen XS, Chen K, Yan Y, Jing H, Chen XQ, et al. Evaluation of diagnostic criteria for atopic dermatitis: Validity of the criteria of Williams et al. in a hospital-based setting. Br J Dermatol. 2001;145(3):428–433.
  159. De D, Kanwar AJ, Handa S. Comparative efficacy of Hanifin and Rajka’s criteria and the UK working party’s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India. J Eur Acad Dermatology Venereol. 2006;20(7):853–859.
  160. Suárez-Fariñas M, Dhingra N, Gittler J, Shemer A, Cardinale I, De Guzman Strong C, et al. Intrinsic atopic dermatitis shows similar TH2 and higher T H17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361–370.
  161. Thijs JL, de Bruin-Weller MS, Hijnen DJ. Current and Future Biomarkers in Atopic Dermatitis. Immunol Allergy Clin North Am. 2017;37(1):51–61.
  162. Stalder JF, Taïeb A, Atherton DJ, Bieber P, Bonifazi E, Broberg A, et al. Severity scoring of atopic dermatitis: The SCORAD index: Consensus report of the european task force on atopic dermatitis. Dermatology. 1993;186(1):23–31.
Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Welcome: