Phenotypes, endotypes and genotypes of atopic dermatitis and allergy in populations of African ancestry on the continent and diaspora

Atopic dermatitis is a complex inflammatory condition characterized by synergist interactions between epidermal and immune related genotypes, skin barrier defects and immune dysregulation as well as microbial dysbiosis. Ethnicity-specific variations in clinical presentation, immune endotypes and genetic susceptibility have been described in diverse populations. We summarize available data with specific consideration of AD in populations of African ancestry. Some highlights include the observation of AD lesions on extensor surfaces, lichen planus-like AD, prurigo type AD and follicular AD in African populations. In addition, a consistent absence of dominant filaggrin gene defects has been reported. The detection of normal filaggrin protein content in AD skin implicates the contribution of alternative mechanisms in the pathogenesis of AD in African patients. Markedly high IgE has been described in paediatric and adult African AD. While Th2, Th22 and Th17 activation in African AD skin shares the same direction as with other populations, it has been noted that the magnitude of activation is dissimilar. Reduced Th17 cytokines have been observed in the circulation of moderate to severe paediatric AD. The most commonly described FLG loss-of-function (LoF) mutations located in the epidermal differentiation complex (EDC) on chromosome 1q21 are rarely identified in African AD. Paediatric AD is characterized by an abundant Th2-related cytokine milieu, and reduced Th17-related cytokines have been observed. Eosinophils, monocytes and total and specific IgE are elevated in the circulation of children with AD. There is a multipolar cytokine profile in adult AD with increased eosinophils and total IgE also noted. Adult AD skin biopsy samples show increased epidermal thickness and spongiosis. The content of filaggrin protein and filaggrin breakdown products such as urocanic acid-1 (UCA1) are unchanged in African AD skin. Filaggrin breakdown products such as pyrrolidone-5-carboxylic acid (PCA) and urocanic acid (UCA) are reduced. Tight junction proteins such as claudin-1 (CLDN1) and claudin-8 (CLDN8) expression is reduced in AD in adult Africans. There is increased influx of Fc epsilon R1 bearing dendritic cells and Langerhans cells as well as increased expression of diverse T cell subsets and related cytokines. Created with BioRender.com.