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Atopic dermatitis (AD) affects patients from all over the world, including all races and skin types. Both environmental and genetic factors play a role in influencing the main features of AD in different populations. For example, AD seems to be more prevalent in Black and mixed race populations compared with Whites. Different genetic backgrounds for AD have been demonstrated in European, African and Asian populations. In this article, we will review the various aspects of AD affecting different populations and racial skin types throughout the world.
Atopic dermatitis (AD) is the most common disease of the skin in childhood. It affects children worldwide, of all races and skin types. In this article, we will review the frequency and genetic mechanisms affecting AD in different populations and racial skin types throughout the world.
The concepts of race and ethnicity are often used interchangeably, and both have overlapping elements.[1, 2] When speaking of race one refers to a combination of physical and phenotypic characteristics, which include skin colour, hair texture, and facial features. Ethnicity encompasses a wider and more complex concept, which implies belonging to a group, or a perception of belonging to a group, based on geographical or ancestral origin, cultural tradition, language or other shared characteristics.
It is difficult to describe skin types according to race and ethnicity. There is no universal agreement on exactly how many races exist. In traditional anthropological studies, five main races are defined: Mongoloid, Caucasoid, Australoid, Negroid and Capoid. A classification by Garn includes nine races: African, Amerindian, Asiatic, Australian, European, Indian, Melanesian-Papuan, Micronesian and Polynesian. These classifications are both too simplistic and do not reflect the richness of skin and general features that humans elicit. In our clinic in Madrid, where we see many patients from Latin America, we notice how different people appear both from different countries, or various regions in one single country (Fig. 1). Not only do their skin colour and features differ, but cultural background also makes a difference to the way their skin looks and is cared for. It is clear that there are many different races, and an accurate classification is virtually impossible. Finally, there are many patients of mixed racial origin, which further complicates classifications.
We used to believe that AD was just one single disease affecting many different races. It is now questioned whether AD itself is in fact a group of different diseases. Both epidemiologic and genetic factors thus may play a role in influencing the main features of AD.
A study of the geographical incidence and prevalence of AD worldwide, and recent trends in the epidemiology of AD, should give a rough estimate of how frequent AD appears in different skin types and races. However, the data should be considered with caution, not only because of the intrinsic difficulties in surveying patients from different cultures, but also the methodology used in the various available studies. For instance, some of the studies estimate the incidence of AD, whereas others measure its prevalence. Furthermore, some studies assess the lifetime prevalence of eczema lesions, whereas others measure the lifetime prevalence of physician-diagnosed AD, the prevalence of self-reported AD (e.g. prevalence of a rash with a typical distribution), or other more specific criteria. Despite all these drawbacks, it becomes obvious that there is a high prevalence of AD in all countries worldwide, and there has been a slight increasing trend in the prevalence of AD during the last 10 years in most countries. Rough estimates from studies in Africa indicate a high prevalence of AD (16.5–20.9%) in children from Morocco, South Africa, Kenya and Nigeria. Similar figures, with modifications due to the study designs, are found in children from Eastern Asia, South-East Asia, Western Asia and Oceania. Most studies come from European countries, where similar figures have been recorded. However, in European countries there are people from many different racial origins and also mixed races, and it is hard to draw conclusions regarding the frequency of AD in the various different races in Europe.
A number of studies have clearly shown a genetic basis for AD. However, cultural and environmental factors are also likely to play a role in the development, triggering and other manifestations of AD. Experts in the field of AD recognize that it is not just a single disease, but a skin condition with numerous different underlying genetic mechanisms and environmental factors, that can have an influence on the frequency of AD in different skin types. Studies in countries where children of many races cohabit, could offer a good estimate of how common AD is in the different races. A US study showed that Blacks and Asian/Pacific Islanders were more likely to attend medical services because of AD than Whites. The proportion of consultations for AD in comparison with all other skin and medical visits was still much higher in Black and Asian/Pacific Islanders than in Whites, supporting the idea that patients of those races suffer more commonly from AD than others. A greater prevalence of eczema in Black and multirace populations compared with Whites has been confirmed in another large eczema prevalence study in the US. These studies, did not take into account whether patients were born in the US or whether they were immigrants. A study carried out in England among children born in London, showed that the prevalence of AD assessed by dermatologist examination in 693 school children was significantly higher in Black Caribbeans than in White, Indian or Pakistani children. However, all these children at study were born in London, and immigration did not play a role in the discrepancy. As a conclusion, we still do not know the exact prevalence of AD in different races, but it seems that, although AD is highly prevalent worldwide, some races may be more prone to develop the disease.
One reason for differential prevalence of AD in different races could be the overall genetic background and the genes responsible for AD in each population. AD is definitely a heterogeneous disorder, which might be explained by different genetic mechanisms of the disease. It is commonly recognized that loss-of-function mutations in filaggrin are a major predisposing factor for developing AD, as well as many other features including acute food allergy, asthma and hay fever. Not only filaggrin null phenotypes are associated with AD but also the number of intragenic copies within the filaggrin gene is important too. Although there are many population studies regarding loss-of-function mutations in filaggrin in AD, much less is known about the distribution of intragenic copy number variations in the AD population. When comparing the specific loss-of-function filaggrin mutations in different populations, it becomes clear that these are different in European, Asian and African countries.[8, 10-14] The most common filaggrin mutations in Europe, R501X and E2422X are only occasionally seen in Asians and Africans. Although many different filaggrin mutations have been reported in Asians, the 3321delA mutation is the only one that has been identified in all the Asian populations studied (Chinese, Japanese, Korean and Taiwanese); this mutation has not been found in Europeans.
Unlike other diseases, in which different mutations within one gene show different phenotypic variations, the large array of loss-of-function filaggrin mutations seem to lead to a single phenotype with slight variations. An explanation of this could be that all the mutations reported lead to truncated filaggrin protein, with loss of the C-terminal region that seems to be key for proper filaggrin processing.
A comparison between the genetic background for AD in different populations might offer some clues for phenotypic variations. A study comparing Singaporean Chinese and Irish populations revealed that filaggrin mutations were found in almost 50% of Irish, but only in 20% of Singaporean Chinese. Furthermore, the two main mutations in Ireland, R501X and 2282del4 accounted for 80% of all filaggrin mutations, whereas they represented only 1% in Singaporean Chinese. A much larger number of different filaggrin mutations were observed in Singaporean Chinese than in Irish patients with AD. This has lead to the postulation that Asians are more subject to mutation pressure than Europeans, in whom both a founder or bottleneck effect may underlie the genetic inheritance.
In a large number of patients studied so far, loss-of-function filaggrin mutations are the only single gene mutation associated with AD. A very significant population of patients with AD remains, in whom a genetic basis has not been located. AD is a clinically heterogeneous disorder, but also a genetically heterogeneous one. It is also likely that many other genetic, epigenetic and racial features will be discovered that will be shown to influence the clinical manifestations of AD.
The discovery of filaggrin mutations has helped to assess a subset of patients with common phenotypic features, such as early-onset and severe AD, high incidence of asthma and other atopic diseases, high incidence of long-term skin disease and a predilection for eczema in exposed areas of the skin, particularly the hands and cheeks. Hyperlinear palms and keratosis pilaris are strong clinical markers of loss-of-function filaggrin mutations (Fig. 2).
In the future, the genetic and environmental background in patients with AD will be elucidated, and these will lead to a more accurate classification of the disease and also will allow for better strategies of management, control and prevention.