PW03-022 - Neutrophilic skin disease and inflammation

Robert Sweet first described a syndrome with a painful, erythematous nodular plaques, neutrophilic dermal infiltrates, fevers and peripheral neutrophilia. This cluster of syndromes became known as Sweet's syndrome. There have been many published cases in children of neutrophilic dermatoses and fever which are labeled as Sweet's syndrome. Recently, however, neutrophilic dermatoses have been associated with some autoimmune and autoinflammatory diseases

Affordable moisturisers are effective in atopic eczema: A randomised controlled trial

Background. Many patients depend on moisturisers issued by public health services in the management of atopic dermatitis (AD).Methods. In a randomised controlled trial of patients with mild to moderate AD, aged 1 - 12 years, study 1 compared aqueous cream v. liquid paraffin (fragrance-free baby oil) as a soap substitute, all patients using emulsifying ointment as moisturiser, and study 2 compared four moisturisers, emulsifying ointment, cetomacrogol, white petroleum jelly and glycerine/petroleum (proportion 1:2; ‘the 1:2  moisturiser’), all using fragrance-free baby oil as soap substitute. Assessments were one quality of life and three AD severity scores, at baseline and weeks 4, 8 and 12. Differences were compared using repeated measures of analysis of variance.Results. In both studies (120 children randomised, 20 in each group of the two trials) disease severity scores declined with time. The only significant difference was in one AD severity score (SCORing Atopic Dermatitis) in study 1, both at baseline and over time (p=0.042 and p=0.022). The groups did not differ with regard to topical steroid use or side-effects. Itching from baby oil applied as soap was reported by four patients in the two studies, the petroleum jelly group had more dropouts than the 1:2 moisturiser group, although this was not statistically significant, and 110 patients (91.7%) completed the trial.Conclusions. The small sample limits generalisability, but the duration was longer than in most AD moisturiser studies. Fragrance-free baby oil as a soap substitute may be better tolerated (if irritation occurs) as a bath additive. The 1:2 moisturiser may be preferable to white petroleum jelly, but both are equivalent to cetomacrogol and emulsifying ointment. Use of accessible moisturisers could reduce the cost of managing mild to moderate AD

Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children

Background Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). Conclusions This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways

Atopic dermatitis and food sensitization in South African toddlers: Role of fiber and gut microbiota

The pathogenesis of atopic dermatitis (AD) is complex and related to allergic responses and defects in skin barrier function. In common with many atopic diseases, the prevalence of AD has been increasing across the world.1 One of the theories for this increase is increased hygiene and urbanization-related changes in the environment, which can affect the human microbiome.2 Previous studies have found associations between the composition of the early gut microbiome and development of atopic conditions, including AD.3 Although the rate of atopic conditions, including AD and food allergy, is increasing on all continents, the prevalence of these diseases is still lower in African countries.1 This is especially interesting because individuals of African origin who live in Western countries, such as African Americans, are at a higher risk for severe AD.4 This variation places Africa in a special position; studying African populations is necessary not only to find ways to prevent increases of allergy conditions in African countries but also to provide important clues to the causes of this global increasing of allergic conditions. Young children who have developed AD in African communities with a low incidence of atopic disease might be the transitional group. In the current study, we have, for the first time to our knowledge, analyzed the fecal microbiota composition of a group of young black African children aged 12 to 36 months old with and without AD living in the same community in Cape Town, South Africa. Our primary goal was to examine whether toddlers with AD and control toddlers from Cape Town have different microbiomes in terms of bacterial richness and diversity. We also aimed to investigate the differences in the relative abundance for different operational taxonomic units between these 2 groups. In our subgroup analyses, we further tested the effect of multiple environmental factors on the gut microbiome in these children

Molecular Epidemiology of Endemic Human T-Lymphotropic Virus Type 1 in a Rural Community in Guinea-Bissau

Human T-Lymphotropic Virus type 1 (HTLV-1) affects millions of people worldwide. It is very similar to Simian T-Lymphotropic Virus, a virus that circulates in monkeys. HTLV-1 causes a lethal form of leukemia (Adult T-cell Leukemia) and a debilitating neurological syndrome (HTLV-associated myelopathy/tropical spastic paraparesis) in approximately 5% of infected people. Based on sequence variation, HTLV-1 can be divided into 7 subtypes (1a–1g) with the Cosmopolitan subtype 1a further subdivided into subgroups (A–E). We examined HTLV-1 diversity in a rural area in Guinea-Bissau, a country in West Africa with a high HTLV-1 prevalence (5%). We found that most viruses belong to the Cosmopolitan subtype 1a, subgroup D, but 2 viruses belonged to subtype 1g. This subtype had thus far only been found in monkey hunters in Cameroon, who were probably recently infected by monkeys. Our findings indicate that this subtype has spread beyond Central Africa. An important, unresolved question is whether persons with this subtype were infected by monkeys or through human-to-human transmission

Human T-lymphotropic virus type 1(HTLV-1) associated infective dermatitis

Human T lymphotropic virus type -1 (HTLV-1) infections are important causes of mortality and morbidity in endemic areas worldwide. There is neither a vaccine specific for the virus nor satisfactory treatment for the associated malignancy or inflammatory syndromes. HTLV-1 associated infective dermatitis (IDH) is a chronic dermatitis that has been observed in a variable proportion of HTLV-1 infected children. IDH may serve as an early clinical marker for HTLV-1 and an indicator of increased risk for developing other HTLV-1 associated conditions such as adult T cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy or transient spastic paraparesis (HAM/TSP). However the mechanisms underlying IDH and the relationships with HAM/TSP and ATLL are poorly understood. We undertook skin biopsies from 14 cases with IDH, and controls which included five asymptomatic carriers (ACs) and 18 healthy uninfected individuals from South Africa. We conducted clinical assessments, proviral load, allergen-specific IgE, peripheral blood and cutaneous T cell and virological analyses. We obtained relevant clinical history and examined all cases and controls based on a pre-formed questionnaire. Despite the partial clinical similarities with atopic dermatitis, the individuals with IDH did not have an increased incidence of atopic disease including asthma or rhinitis. Furthermore house dust mite-specific IgE levels were not elevated in the cases compared to the controls, suggesting that atopy is not a predisposing factor for the development of IDH in HTLV-1 infected individuals. Circulating proviral load was significantly higher in those with IDH compared to asymptomatic carriers and skin biopsy revealed acanthosis, and lymphocytic epidermotropism associated with a superficial perivascular and periadnexal lymphocytic infiltration of CD8+, and CD4+ T cells. Furthermore IDH associated with an infiltrate of epidermal and dermal FoxP3+ T cells and lesional down-regulation of filaggrin expression compared to non-lesional skin. We did not observe an elevation of pro-inflammatory cytokines in the sera of individuals with IDH compared to the controls. We investigated integration patterns in the skin and blood of 10 cases with IDH, and two asymptomatic carrier (AC) individuals from South Africa. We first showed that the virus is present in the skin at high levels (total mean levels of 47.09 proviral copies per 1000 cells) as comparable to that which has been observed in blood (total mean levels 137 proviral copies per 1000 cells). Using a high throughput Illumina sequencing system in collaboration with Professor Bangham, we mapped and quantified the relationship between oligoclonal proliferation of HTLV-1 infected T cells in the skin and blood of IDH patients. It was found that in IDH, a selective outgrowth of certain clones is favoured, supporting the possibility of skin-specific factors exerting positive selection on proliferation. In IDH, there was not a preferential integration of the provirus in transcriptionally active regions of the gene sites, as had been observed in other HTLV-1 associated conditions. These observations imply that the selection forces that favour oligoclonal proliferation of HTLV-1+ T cells differ fundamentally between simple HTLV-1 infection and other events associated with the dermatitis. In conclusion, these data show that HTLV-1 is not associated with an atopic diathesis. Given the lack of elevated pro-inflammatory cytokines and presence of a cutaneous infiltrate of FoxP3+ T cells, the findings suggest that high levels of HTLV-1 replication promotes a regulatory environment leading to filaggrin down-regulation, cutaneous susceptibility to infection, and secondary inflammatory skin disease. Viral integration patterns would support the presence of skin-specific positive selection, perhaps eventually leading to expansion of particular clones with the potential to develop towards ATLL. It remains to be explained whether the high viral load in IDH changes over time, more specifically in the steps leading to ATLL.</p