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Differences in the Clinical Phenotype of Atopic Eczema Among Age Groups and Ethnicities

Differences in the Clinical Phenotype of Atopic Eczema Among Age Groups and Ethnicities

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease presenting amongst a variety of ethnicities and age groups. The pathophysiology of this disease involves a complex interplay between genetics, immunologic factors, and skin barrier dysfunction, and the precise mechanism of disease is not clear. Due to the differences in phenotype of this disease across various age groups and ethnicities, diagnosis can sometimes be challenging. Thus, it is of utmost importance that the clinician be aware of the various ways in which AD can present so that early and accurate diagnosis and treatment can be implemented.

Higher Prevalence and Severity in Skin of Color  

AD places a very high burden on black patients. A study looking at eczema prevalence in the United States showed a greater prevalence of eczema in black populations compared with whites (15.9% vs 9.7%).1 In another study, there was a higher prevalence of AD in black Caribbean patients living in London, United Kingdom, than in whites.2 Additionally, studies have shown that black patients with AD are likely to have more severe AD than their white counterparts.3,4

Possible explanation for higher prevalence and severity is that the barrier function of black skin may differ from white skin. For example, black patients have the lowest ceramide-to-cholesterol ratio among different ethnic groups, which is proposed to contribute to decreased epidermal barrier function.5 Their skin also exhibits greater transepidermal water loss than white skin.6 Interestingly, the prevalence of the two most common filaggrin mutations that contribute to AD in the general population was lower in patients of African descent than in those of European descent, suggesting a different genetic susceptibility to the disease.7

NEA Feature Figure 1A, 1B

The prevalence of AD in Asian adults is up to 11%, which is higher than that of AD in Caucasian adults as well.8,9 A study of AD in a Japanese population showed a prevalence of 24% in children from ages 5 to 6 and up to 11% in the 16- to 18-year-old age group.10 One study showed that Asians/Pacific Islanders and blacks were 7 times more likely to be diagnosed with AD at an office visit, further affirming that this disease afflicts other races more commonly than whites.11 

The Dermatology Life Quality Index (DLQI) is a helpful standardized tool used to understand the extent to which a dermatologic disease impairs quality of life, with decreased scores indicating less quality of life impairment. A study in Michigan using patients diagnosed with AD ranging from 4 to 70 years of age showed mean DLQI scores of 6.6 for women and 6.8 for men.12 In a different study of Korean patients seen at dermatology clinics, mean DLQI scores were 10.7.13 These results suggest that individuals of Asian descent diagnosed with AD may have greater quality-of-life impairment than the general population.

The difference in prevalence and severity of AD in Asians may be attributable to many factors, including genetics. The most common filaggrin mutations present in up to 10% of Caucasians was found to be rare in Asian populations.14-16 

Morphology and Distribution of the Rash

The clinical presentation of AD in the general population typically varies based on age. Children between 3 months and 2 years of age typically have erythematous, papulovesicular, scaly lesions that may ooze. The lesions are classically distributed in the cheeks, neck, scalp, and extensor surfaces.17 AD in children from 2 to 12 years of age typically exhibits acute eczematous lesions as well; however, some lesions may be chronic with some lichenification. In this age group, eczematous lesions are usually located in flexural surfaces (the neck, feet, and hands) and in the periorificial area. AD in adolescents and adults aged 12 to 60 years is usually seen in the head, neck, flexural areas, and periorbital region. Those with longstanding disease may exhibit erythroderma. Finally, AD in elderly patients older than 60 years is characterized by extensive eczematous nummular lesions. Lesions sometimes spare the flexural surfaces.18,19NEA Feature Figure 2

African American patients are at a higher risk of being diagnosed with AD at a later age due to more subtle findings and unusual presentations of the disease. A scattered, micropapular rash, annular and localized to the extensor surfaces and trunk, is commonly seen in these patients (Figure 13).3,20 Periumbilical lesions that can mimic contact dermatitis to nickel have been described as well.21 In addition, it has been observed that African Americans have a higher tendency to present with lichenification and prurigo nodularis than other ethnic groups.3 In contrast to white skin, black skin is less likely to develop obvious erythema, and post-inflammatory hypo- or hyperpigmentation are more common sequelae of AD in darker skin.22,23

AD lesions in Asian patients tend to be more demarcated, with increased scaling and lichenification, as compared with whites patients.24,25 Asian patients with AD also have a more psoriasiform phenotype (Figure 2) compared with European patients with AD, with more prominent epidermal hyperplasia, elongated rete ridges, and parakeratosis seen on histology. These differences in phenotype were identified by Noda et al,24 who performed genomic profiling and immunohistochemistry on biopsy specimens from 52 patients with AD. Skin biopsy specimens showed significantly higher induction of TH17- and TH22-related cytokines (ie, IL-19, IL-22) in Asian AD skin compared with those seen in European patients with AD. These findings may account for the differences in phenotype seen in Asian AD skin, as IL-19 and IL-22 are known inducers of epidermal hyperplasia and parakeratosis.25

Common features associated with AD across all ethnicities include skin xerosis or dryness and generalized atopy. Patients may also exhibit palmar hyperlinearity, Dennie-Morgan lines, and Herthoge sign.26 The association of AD with the presence of an infraauricular fissure has been well established amongst both young and old patients (Figure 3). Furthermore, it was observed that the presence of an infraauricular fissure is actually an indicator of disease severity, with a more severe fissure indicating greater disease activity.27 Unfortunately, patients with AD are also very susceptible to infection, in particular staphylococcal species and herpes simplex virus.27,28 Nummular eczema is a variant of AD that occurs in adults characterized by ovoid eczematous patches that may present in nonflexural areas on the face, trunk, and extremities (Figure 4).29 Other cutaneous disorders associated with AD include ichthyosis vulgaris and keratosis pilaris.30 

Implications for Treatment of AD in Different Phenotypes of AD 

Currently, there are no guidelines recommending different first-line treatments of AD based on ethnic or racial background. However, in the black patient population, structural differences causing reduction of the skin’s barrier function have been noted, suggesting that aggressive attempts to maximize the barrier function by optimizing skin care is of particularly high importance in preventing flares in this population. Further study into the exact mechanism of the structural differences or differential genetic and immunologic factors in this population may provide a framework for future targeted therapies. 

Infraauricular fissure in patientDevelopments in biologic therapy have yielded exciting results for treatment of moderate to severe AD. Dupilumab (Dupixent), a monoclonal antibody that targets the IL-4 receptor, has been shown in large randomized controlled trials31-33 to reduce symptoms and improve quality of life compared with placebo in those with moderate to severe AD. These trials, SOLO1, SOLO2, and LIBERTY AD CHRONOS were carried out in multiple countries in North America, Europe, and Asia and each included 20% to 27% Asian and 5% to 7% black participants. No comparisons of response or secondary measures were provided between racial groups in these studies.31-33 Given the increased prevalence of severe AD in black and Asian patients, the use of targeted biologic therapeutics has a promising opportunity to reduce the burden of the disease in these populations. Predominance of the TH17 lymphocytes and related cytokines (IL-17A, IL-19, IL-22) in the Asian population may have implications for differential response to current biologic therapy.34 Secukinumab (Cosentyx) and ixekizumab (Taltz) are monoclonal antibody therapies targeting IL-17A and are very effective treatments of psoriasis and related disorders.35,36 Further research into the potential for these and other therapeutics targeting the TH17 pathway may allow for more efficacious therapies for AD in the Asian population. 

Conclusion 

With that information in mind, it is especially important to go the extra mile to use the best possible moisturizing agents and barrier repair strategies to treat AD in patients with skin of color, particularly those with African ancestry, to ensure that we are doing all we can to improve the barrier.Nummular eczema, Figure 4

AD may present a clinical diagnostic challenge due to variations in presentation, distribution, and severity of disease between ethnic groups. It is important for a dermatologist to recognize these potential differences so as to provide a timely diagnosis and tailor appropriate treatment regimens for their patients of all racial and ethnic backgrounds. Structural and molecular distinctions have been noted between ethnic groups with AD, alluding to the potential for differential therapeutic targets. Given the higher prevalence and severity of AD in black and Asian patients, further research into the factors that are distinct to these populations is necessary for the development of appropriately targeted therapies.

Dr Yosipovitch is a professor at the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and director of Miami Itch Center of the University of Miami Miller School of Medicine in Miami, FL. Ms Golpanian is a future MD candidate and research fellow at the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center of the University of Miami Miller School of Medicine. Mrs Fourzali is a future MD candidate and research fellow at the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center of the University of Miami Miller School of Medicine. Dr Tey is head of the research division and senior consultant at the National Skin Centre, an adjunct associate professor at Yong Loo Lin School of Medicine, and an assistant professor at Lee Kong Chian School of Medicine in Singapore.

Disclosure: Dr Yosipovitch is scientific board member of Menlo, Trevi, Sienna, Sanofi, Regeneron, Galderma, Pfizer, Novartis, Bayer, Kiniksa, Eli Lilly, and Ortho. He receives research support by Pfizer, Sun Pharma, Leo, Menlo, and Kiniksa. The other authors report no relevant financial relationships.

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