Key points
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Atopic dermatitis is one of the most common inflammatory diseases of the skin, with both genetic and environmental etiologies.
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The prevalence of atopic dermatitis is increasing globally due to changes in climate, microbes, urbanization, among other factors.
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Atopic dermatitis can have broad effects on mental health, quality of life, development, and psychosocial function, which can affect patients and their families.
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The financial burden of atopic dermatitis is high with both primary and secondary costs.
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Access to dermatologists, especially pediatric dermatologists, is limited, and vulnerable patients are often disproportionately affected with limited access to specialist care.
Introduction
Atopic dermatitis is an inflammatory skin disorder. Descriptions of atopic dermatitis are found in Roman history dating back to 69 to 140 CE. The term eczema , meaning “boiling over,” was first introduced in 543 CE to describe an “inward heat, which drives off the humors of the body from its surface like the seething of a boiling fluid” ( ). The term atopic dermatitis was introduced into the dermatology medical lexicon in 1933 by Fred Wise and Marion Sulzberger based on the term atopy to describe the association between asthma and allergic rhinitis ( ). This chapter delineates the epidemiology, which by definition deals with the incidence, prevalence, distribution, and sum of factors controlling the presence and absence of atopic dermatitis.
Prevalence, distribution, and generally recognized factors
Atopic dermatitis is now one of the most common inflammatory skin disorders both in the United States and worldwide. Prevalence estimates for atopic dermatitis range from 10% to 13% for children and 2% to 10 % for adults, as prevalence of atopic dermatitis decreases with age ( ). The severity of atopic dermatitis also tends to decrease with age. One pediatric study from 2017 evaluated the severity of atopic dermatitis in the United States. This study found that among pediatric patients with atopic dermatitis, 67% had mild disease, 26% had moderate disease, and 7% had severe disease, which correlates with 2.98 million children in the United States with moderate-to-severe disease ( ). The prevalence estimates vary both globally and within different settings in the United States. For example, prevalence estimates vary with urban versus rural living and within different socioeconomic populations. Globally, prevalence estimates are as low as 0.9% in India and as high as 11% to 24% in Japan, 24.6% in Colombia, and 30.48% in China ( ). Prevalence estimates may be lower when using diagnostic criteria studies, such as the Hanifin and Rajka scales, than when studies are conducted with in-person dermatologists ( ).
US prevalence estimates for atopic dermatitis also vary within different populations. Blacks and Hispanics have a higher prevalence of atopic dermatitis even after controlling for potential confounding factors, such as household incomes, health insurance, and parental education levels ( ). Higher rates of more persistent, early-onset atopic dermatitis and higher rates of late-onset atopic dermatitis may contribute to the higher prevalence of atopic dermatitis seen in these populations ( ). Increased severity of atopic dermatitis is associated with higher household incomes, the oldest child in the family, homes with a single mother, lower parental education levels, lower parental emotional health, and in areas with dilapidated housing and garbage on the streets ( ).
There are multiple names and clinical definitions for atopic dermatitis that contribute to differences in prevalence estimates ( ). Overall, the prevalence of atopic dermatitis is increasing. This is a true increase in prevalence, not simply due to an increase in minor signs and symptoms or in the medical profession’s use of the words eczema and dermatitis ( ). A study in Japan found that among Japanese children, the prevalence of atopic dermatitis has doubled in the past 20 years, and among 18-year-olds the prevalence is over five times greater than it was 20 years ago ( ). In the United States, prevalence estimates have also shown an upward trend with a possible plateau around 2013 ( ). This increase in prevalence has been attributed to changes in urbanization, pollution, microbes, climate, and diet.
With urbanization, the prevalence of atopic dermatitis in developing nations approaches that of developed nations; increasing trends toward urbanization may contribute to the overall increased prevalence of atopic dermatitis ( ). The leveling off of prevalence of atopic dermatitis with urbanization supports a role for environmental factors in the pathogenesis of atopic dermatitis ( ). Atopic dermatitis has a higher prevalence in cities than in the countryside. The hygiene hypothesis proposes that exposure to microbes early in life may induce immunologic tolerance and thereby decrease the risk of allergy development ( ). Urbanization may be associated with changes in hygiene, different microbial infections, increased use of antibiotics, and different exposures to diet and new allergens, which may contribute to the increased prevalence of atopic dermatitis in urban areas.
Urbanization may further be associated with an increased prevalence of atopic dermatitis secondary to the effects of pollution. Both indoor and outdoor pollution are known to exacerbate atopic dermatitis. Similarly, tobacco smoke exposure is associated with atopic dermatitis. Tobacco smoke increases levels of proinflammatory cytokines and reduces levels of antiinflammatory cytokines, contributing to oxidative damage, which decreases the skin barrier and has an irritant effect on the skin. Given that up to one-third of atopic dermatitis occurs within the first year of life, prenatal exposure to air pollution may play a role in the development of atopic dermatitis. One study showed that the prevalence of atopic dermatitis during the first year of life doubles with prenatal exposure to fine particulate matter and with postnatal exposure to tobacco smoke ( ).
Changes in microbes may contribute to differences in atopic dermatitis in urban areas compared to more rural areas. Exposure to bacterial endotoxins from dogs, farm animals, and commensal microbes may be protective against developing allergies ( ). A 2013 study examined pacifier use in infants. Infants whose parents sucked the pacifier to clean it were less likely to develop asthma, eczema, and sensitization than infants whose parents did not clean the pacifier by sucking it, suggesting that the transfer of salivary microbiota may stimulate the immune system in infants and ultimately reduce the risk of allergy development ( ). Similarly, along the lines of the hygiene hypothesis, exposure to microbes on dishes may reduce the incidence of atopic dermatitis. A 2015 study found that allergic diseases were less common in children whose families hand-washed dishes compared to those who used a dishwashing machine, perhaps due to increased microbial exposure in the less-efficient hand-washing technique ( ). The skin microbiome may contribute to differences in atopic dermatitis phenotypes. Antibiotic use is associated with an increased risk of atopic dermatitis, which may be related to changes in the microbiome. A recent study found increased levels of Staphylococcus aureus in atopic dermatitis patients compared to nonatopic controls. Furthermore, the study found a positive correlation between S. aureus levels and transepidermal water loss in patients with atopic dermatitis and food allergies but not in patients with atopic dermatitis alone or in nonatopic controls. These data suggest a potential link between the skin microbiome and atopic phenotypes ( ). There has been no proven association between vaccinations and the prevalence of atopic dermatitis ( ).
In regard to climate, symptoms of atopic dermatitis worsen with increasing latitude and with decreasing outside temperature. This is thought to relate to the immunosuppressive effects of ultraviolet (UV) light. UV light aids in the conversion of trans -urocanic acid in filaggrin into cis -urocanic acid, which has an immunosuppressive effect. UV light has antiinflammatory effects by downregulating Langerhans cells and decreasing proinflammatory T-cell cytokines in the skin. Additionally, increased levels of vitamin D in response to sun exposure may improve atopic dermatitis. Vitamin D deficiency has been associated with more severe atopic dermatitis in photo-protected areas suggestive of a potential local protective effect from vitamin D ( ).
Atopic dermatitis is less common in developing countries, which may in part be related to diet. The traditional Western diet, consisting of refined cereals, red and preserved meats, and high in saturated and unsaturated fatty acids may be associated with an increased prevalence of atopic dermatitis ( ). More specifically, a high intake of fish during pregnancy has been shown to lower the risk of atopic dermatitis. There is a similar risk reduction in children who have a high intake of fish. This risk reduction is likely related to the high content of antiinflammatory n-3-polyunsaturated fatty acids. Similarly, some studies suggest a possible protective effect with an increased intake of fresh fruit and a negative effect with the intake of fast foods. However, despite these potential correlations, strict diet control has not shown to be effective in the management of atopic dermatitis. Nutrition and diet as a factor of atopic dermatitis are further discussed in Chapter 8 .
Along the lines of increased inflammation worsening atopic dermatitis, increased screen time on electronic devices, which may contribute to obesity and inflammatory adipokines, has also been associated with increased atopic dermatitis ( ). Obesity has been shown to be associated with an increased incidence of bacterial and Candida skin infections as well as multiple inflammatory disorders, including psoriasis, rosacea, and hidradenitis suppurativa. A 2015 meta-analysis showed an association between increased weight and the prevalence of atopic dermatitis in North America and Asia, though a causal link has yet to be determined ( ). The data regarding breastfeeding for prevention of atopic dermatitis is controversial, with some studies suggesting that exclusive breastfeeding may actually increase the risk of atopic dermatitis due to decreased exposure to microbes early in life ( ). The data regarding the role of probiotics in reducing atopic dermatitis have also been mixed; however, maternal supplementation with probiotics during breastfeeding may play a role in reducing the incidence of atopic dermatitis by increasing antiinflammatory immunoregulatory factors in breast milk ( ). Furthermore, atopic dermatitis is a chronic inflammatory disorder, and like other chronic inflammatory conditions may increase the risk of malignancy, though evidence is contradictory, and there are many potential confounding factors ( ).
Some studies suggest that a decreased remission rate may also explain the increasing prevalence of atopic dermatitis. This decreased remission rate is attributed to an increase in the environmental factors previously described, social stressors, a fear of using topical corticosteroids, and more widespread use of home remedies, which often lack scientific evidence ( ). Epidemiologic trends, potential contributors, and possible action items are summarized in Table 4.1 .
| Epidemiologic trends | Potential contributors | Possible actions items |
|---|---|---|
| Blacks and Hispanics have higher prevalence |
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| Increasing prevalence in developing nations |
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| Decreased remission rate |
|
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Genetics as a controlling factor
Genetics plays a strong role in the pathogenesis of atopic dermatitis, with genetic alterations accounting for 90% of the susceptibility of early-onset atopic dermatitis ( ). The concordance rate for atopic dermatitis is significantly higher in monozygotic twins at 77% compared to only 15% in dizygotic twins ( ). Furthermore, parental history of atopic dermatitis is a stronger predictor for developing atopic dermatitis than a personal history of either asthma or allergic rhinitis. For many years, atopic dermatitis was thought to result from immunologic defects resulting in a defective skin barrier, a theory known as the inside-outside hypothesis ( ). It is now known that genetics do play a strong role in the development of atopic dermatitis, more likely through an outside-inside mechanism with defects affecting the skin barrier rather than immunology alone.
FLG encodes the protein filaggrin, or filament-aggregating protein. FLG is expressed throughout all layers of the epidermis, and filaggrin is an important structural component of the stratum corneum ( ). Breakdown products of filaggrin play an important role in epidermal hydration, lipid processing, and barrier function ( ). Mutations in FLG are an important predisposing factor for childhood eczema. FLG mutations are present in 10% to 30% of atopic dermatitis patients, and genome-wide association studies suggest multiple other loci that may play a role in the development of atopic dermatitis ( ).
FLG mutations are overexpressed in patients with atopic dermatitis compared to those without atopic dermatitis. In the atopic dermatitis cohort, there is a sixfold overrepresentation of null FLG alleles: 42% of patients in the atopic dermatitis cohort carry null mutations in FLG , whereas as only 8.8% of the general population carry null mutations in FLG ( ). An estimated 20% to 50% of European and Asian children with moderate-to-severe atopic dermatitis have at least one FLG mutation ( ).
Patients with FLG mutations tend to have earlier-onset atopic dermatitis, greater disease severity, and are more likely to have disease persistence into adulthood. Carriers of FLG mutations are also at increased risk for developing allergic and irritant contact dermatitis, asthma, hay fever, and food allergies ( ). FLG is not expressed in the gastrointestinal or bronchial mucosa, so the increased risk for food allergies and asthma associated with filaggrin mutations supports the hypothesis that cutaneous sensitization and inflammation contribute to systemic development of atopy ( ).
Deficiencies in SPINK5 , which encodes lymphoepithelial Kazal-type 5 (LETK1) may also play a role in the development of atopic dermatitis and Netherton syndrome. LETK1 is a serine protease inhibitor expressed in mucosal and epithelial surfaces. LETK1 normally inhibits kallikreins, which are important in regulating skin desquamation, inflammation, and maintaining the skin barrier ( ). Increased serine protease results in proteolytic cleavage of the stratum corneum ( ).
In addition to FLG and SPINK5 , genome-wide association studies have found many genes that are associated with atopic dermatitis. Some of the proteins encoded by these genes include mattrin, which regulates lamellar body assembly and is encoded by TMEM79 , zinc-dependent metalloproteinases encoded by ADAMTS , kinesin found in cilia encoded by KIF3A , and proteins involved in epithelial tissue and germ cell differentiation encoded by OVOL1 ( ). A recent study examined different phenotypes of atopic dermatitis. Patients with atopic dermatitis and food allergies had increased amounts of keratin 5, 14, and 16 in the skin compared to patients with atopic dermatitis and no food allergies and compared to nonatopic controls. These data suggest that variation in protein expression may contribute to different atopic dermatitis phenotypes ( ). There may also be differences in barrier components among atopic dermatitis phenotypes. Atopic dermatitis patients with food allergies may have lower levels of filaggrin and lower proportions of omega-hydroxy fatty acid sphingosine ceramide content compared to atopic dermatitis patients without food allergies and nonatopic controls ( ). Genes, proteins and their respective functions, and mutational effects in atopic dermatitis are summarized in Table 4.2 .
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