Skin and nasal bacterial dysbiosis is common in children with atopic dermatitis (AD). However, there is limited data of these bacterial changes in sub-Saharan children with AD. Therefore, this study investigated the bacterial alterations in skin and nasal bacterial communities in AD compared to healthy children in rural and urban South African settings. Staphylococcus aureus was more common in children with AD (cases) than healthy children (controls). S. aureus carriage was also associated with increased disease severity. Using spa typing, we also showed that cases and controls were colonised by distinct spa types. This led us to comprehensively explore genomic differences of S. aureus in cases and controls using whole-genome sequencing. Here, we showed that S. aureus strains from cases and controls had distinct genomic features, with cases harbouring genes associated with antibiotic resistance, DNA damage repair and virulence while controls had genes associated with adhesion. Recent reports indicate the potential role of coagulase-negative Staphylococcus (CoNS) in AD pathology. This study found that CoNS and S. aureus were commonly co-carried on nonlesional skin among cases (regardless of location) and anterior nares among urban cases than the control group. The carriage of S. capitis on nonlesional skin and anterior nares was positively associated with more severe disease in both rural and urban cases. 16S rDNA amplicon sequencing analysis revealed that bacterial diversity was higher on the nonlesional skin and anterior nares of controls. Bacterial community structure differed on lesional skin, nonlesional skin and anterior nares based on AD disease status. The relative abundance of Streptococcus, Granulicatela, Veillonella and Prevotella was high in lesional skin specimens, Anoxybacillus and Cutibacterium on nonlesional skin, and Staphylococcus, Veillonella and Sphingomonas in the anterior nares among cases Overall, the findings presented in this thesis indicate that S. aureus and other CoNS, particularly S. capitis, may predominate among cases and are associated with increased disease severity. However, the increased relative abundance of genera such as Streptococcus, especially among skin samples, indicates that other bacterial genera may be contributing to disease activity on lesional skin in AD than the traditionally reported Staphylococcus.

Atopic dermatitis (AD) typically develops in patients with a history of allergic ailments, and is characterised by an itchy, inflammatory skin condition with scaling, lichenification, papules, excoriations and pruritus. In AD patients a chronic relapsing inflammatory condition is seen, associated with IgE hyper production. AD flares are largely triggered by environmental factors. However, the exact etiology of AD is unclear and there is a pressing need for new treatment regimens as AD is a chronic condition and requires long term treatment. Historically Aloe has been used to treat skin conditions as well as a variety of other diseases. To further explore the pathogenesis and treatment of AD, Balb/c mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB) for atopic dermatitis induction. Thereafter, mice were treated with either Aloe ferox or Aloe vera applied daily on the dorsal skin for 10 consecutive days. A placebo gel was used for the control mice. Blood was collected at the end of the treatment period and serum IgE levels measured. Serum IgE levels were significantly lowered in the Aloe ferox group than in the Aloe vera group. This study demonstrated Aloe’s immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted

No / Background  Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. Objectives  To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. Methods  hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. Results  Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL−1 of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. Conclusions  Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing – thus indicative for contact of the epidermis with serum components.

Background: Lifestyle and environmental factors are known to contribute to allergic disease development, especially very early in life. However, the link between diet composition and allergic outcomes remains unclear. Methods: In the present population-based cohort study we evaluated the dietary intake of 10-year-old children and analyses were performed with particular focus on atopic dermatitis or food allergy, allergic diseases known to be affected by dietary allergens. Dietary intake was assessed via semi-quantitative food frequency questionnaires. Based on these data, individual nutrient intake as well as children’s Dietary Inflammatory Index (C-DIITM) scores were calculated. Information about atopic manifestations during the first 10 years of life and confounding factors were obtained from standardized questionnaires during pregnancy and annually thereafter. Results: Analyses from confounder-adjusted logistic regression models (n = 211) revealed that having atopic outcomes was associated with having a pro-inflammatory pattern at the age of 10 years: OR = 2.22 (95% CI: 1.14–4.31) for children with atopic dermatitis and OR = 3.82 (95% CI: 1.47–9.93) for children with food allergy in the first 10 years of life Conclusion: A pro-inflammatory dietary pattern might worsen the atopic outcome and reduce the buffering capacity of the individual against harmful environmental exposures or triggers. For pediatricians it is recommended to test for the individual tolerance of allergenic foods and to increase the nutrient density of tolerable food items to avoid undesirable effects of eating a pro-inflammatory diet.