George Varigos

Atopic eczema: its impact on the family and financial cost

OBJECTIVE To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management. DESIGN Cross sectional survey. SETTING Paediatric dermatology and paediatric diabetology outpatient clinics. PATIENTS Parents of 48 randomly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES The impact on family score, the reported cost of relevant medical treatments, medical consultations, relevant hospitalisation, and income loss. RESULTS Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children. A conservative estimate of the annual personal financial cost of managing mild, moderate, and severe eczema was Aus

IL-4 and interferon-gamma production in children with atopic disease

330, 818, and 1255, respectively. The financial cost to the community for the management of atopic eczema in the study groups was greater. The personal financial cost of managing eczema was greater than for asthma. CONCLUSION Childhood atopic eczema has a profound impact on the social, personal, emotional, and financial perspectives of families.

IL-4 production is increased in cigarette smokers.

In vitro studies have implicated reciprocal roles for IL‐4 and interferon‐gamma (IFN‐γ) in the regulation of IgE production. As elevated IgE is a major feature of atopic disease, an important question is whether an imbalance of IL‐4 and IFN‐γ is present in vivo. The production of IL‐4 and IFN‐γ in phytohaemagglutinin (PHA)‐stimulated peripheral blood mononuclear cell cultures from atopic children was examined to determine if there is an increased production of IL‐4 and/or a reduced production of IFN‐γ. Highly atopic children with IgE >600 U/ml produced significantly more IL‐4 and less IFN‐γin vitro than age‐matched non‐atopic controls. Production of IL‐4 and IFN‐γ in mildly atopic children was equivalent to controls. These findings indicate that highly atopic children have an imbalance of IL‐4 and IFN‐γ production and that the degree of imbalance relates to severity of the atopic state. The ratio of in vitro IL‐4: IFN‐γ production correlated positively with serum IgE, which suggests that the balance of these two cytokines is a factor in the regulation of IgE, in vivo. It remains to be determined whether this imbalance of IL‐4 and IFN‐γ in the highly atopic children is the cause or result of the disease process.

The effect of a low glycemic load diet on acne vulgaris and the fatty acid composition of skin surface triglycerides.

Cigarette smoking has been associated with both increases in serum levels of total IgE and an increased risk of developing allergic‐like symptoms. IL‐4 and interferon‐gamma (IFN‐γ) have reciprocal roles in the regulation of IgE synthesis, and as such prompted us to evaluate, in smokers, the production of these two cytokines. We demonstrate that phytohaemagglutinin (PHA)‐induced IL‐4 production by peripheral blood mononuclear cells (PBMC) of smokers (n= 19) is significantly higher than that of non‐smokers (n=10, p < 0·005). In addition, PBMC from heavy smokers, defined by the number of cigarettes smoked per day, produced significantly higher levels of IL‐4 than those of light smokers. No difference between the groups was found for IFN‐y production. Our data suggest an imbalance in cytokine production occurring in individuals who smoke. This imbalance, favouring IL‐4 production, may be part of the mechanism responsible for the observed increases in serum IgE and allergic‐like symptoms associated with cigarette smoking.

Epidemiology and Impact of Childhood Molluscum Contagiosum: A Case Series and Critical Review of the Literature

BACKGROUND Dietary factors have long been implicated in acne pathogenesis. It has recently been hypothesized that low glycemic load diets may influence sebum production based on the beneficial endocrine effects of these diets. OBJECTIVE To determine the effect of a low glycemic load diet on acne and the fatty acid composition of skin surface triglycerides. METHODS Thirty-one male acne patients (aged 15-25 years) completed sebum sampling tests as part of a larger 12-week, parallel design dietary intervention trial. The experimental treatment was a low glycemic load diet, comprised of 25% energy from protein and 45% from low glycemic index carbohydrates. In contrast, the control situation emphasized carbohydrate-dense foods without reference to the glycemic index. Acne lesion counts were assessed during monthly visits. At baseline and 12-weeks, the follicular sebum outflow and composition of skin surface triglycerides were assessed using lipid absorbent tapes. RESULTS At 12 weeks, subjects on the experimental diet demonstrated increases in the ratio of saturated to monounsaturated fatty acids of skin surface triglycerides when compared to controls [5.3+/-2.0% (mean+/-S.E.M.) vs. -2.7+/-1.7%, P=0.007]. The increase in the saturated/monounsaturated ratio correlated with acne lesion counts(r=-0.39, P=0.03). Increased follicular sebum outflow was also associated with an increase in the proportion of monounsaturated fatty acids in sebum (r=0.49, P=0.006). CONCLUSION This suggests a possible role of desaturase enzymes in sebaceous lipogenesis and the clinical manifestation of acne. However, further work is needed to clarify the underlying role of diet in sebum gland physiology.

Topical diclofenac in hyaluronan gel for the treatment of solar keratoses

Abstract:  Parents of 30 children with clinically diagnosed molluscum contagiosum were surveyed to assess their perception of the condition, its treatment, its impact on their everyday lives, and on the children themselves. Among parents, 82% reported that molluscum contagiosum concerned them moderately or greatly. Concerns focused on physical issues associated with the infection, such as scarring, itching, chance of spread to peers, pain, and the effects of treatments. Quality of life was not affected. Molluscum contagiosum was most common among school‐age children. Eighteen of 29 respondents swam in public pools, a common activity in children of this age. All epidemiologic studies of molluscum contagiosum in otherwise healthy individuals, published since 1966, have been critically reviewed herein. The review confirms an association between swimming pool use and molluscum contagiosum. Age, living in close proximity, skin‐to‐skin contact, sharing of fomites, and residence in tropical climates were also associated with higher rates of infection while sex, seasonality, and hygiene showed no such association.

Border detection in dermoscopy images using hybrid thresholding on optimized color channels.

This randomized, double‐blind, placebo‐controlled study assessed the efficacy and safety of a topical gel containing 3% diclofenac in 2.5% hyaluronan in 150 patients with solar keratoses (SK). The active treatment was compared with the vehicle only, hyaluronan gel, as placebo over a 12‐week period. Patients in both groups applied the active treatment or placebo to a targeted area of skin (0.25 g b.d.). At 12 weeks the mean lesion‐count reduction in the targeted area was not significantly different between treatments. However, at post‐termination follow up (16 weeks), there was a highly significant decrease in the number of lesions, 6.2 ± 7.5 standard deviations (SD) (56.1% reduction) in the active treatment group compared with 2.4 ± 4.3 SD (23.6% reduction) in the placebo group (P < 0.001). Other efficacy measures (complete lesion resolution, >50% lesion reduction) were also significantly different (P < 0.01) between treatments at 16 weeks. In conclusion, topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated in this study, suggesting a role for this therapy in the treatment of SK.

Eczema workshops reduce severity of childhood atopic eczema

Automated border detection is one of the most important steps in dermoscopy image analysis. Although numerous border detection methods have been developed, few studies have focused on determining the optimal color channels for border detection in dermoscopy images. This paper proposes an automatic border detection method which determines the optimal color channels and performs hybrid thresholding to detect the lesion borders. The color optimization process is tested on a set of 30 dermoscopy images with four sets of dermatologist-drawn borders used as the ground truth. The hybrid border detection method is tested on a set of 85 dermoscopy images with two sets of ground truth using various metrics including accuracy, precision, sensitivity, specificity, and border error. The proposed method, which is comprised of two stages, is designed to increase specificity in the first stage and sensitivity in the second stage. It is shown to be highly competitive with three state-of-the-art border detection methods and potentially faster, since it mainly involves scalar processing as opposed to vector processing performed in the other methods. Furthermore, it is shown that our method is as good as, and in some cases more effective than a dermatology registrar.

The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms.

An intervention study was conducted to assess the effectiveness of a nurse‐led eczema workshop in reducing the severity of atopic eczema in infants, children and adolescents. Ninety‐nine new patients referred to the Dermatology Department of The Royal Childrens Hospital in Melbourne, Australia, for the management of atopic eczema were randomized to receive care from an eczema workshop or a dermatologist‐led clinic. Patients were followed‐up 4 weeks after the intervention. The primary outcome was the severity of eczema as determined by scores obtained using the Scoring of Atopic Dermatitis (SCORAD) index at a 4‐week follow‐up visit. The secondary outcome was a comparison of treatments used in both clinics. At the 4‐week review the mean improvement in SCORAD was significantly greater in those patients attending the eczema workshop than those attending the dermatologist‐led clinic (−9.93, 95% confidence interval −14.57 to −5.29, P < 0.001). Significantly more patients from the eczema workshop improved from moderate severity eczema at baseline to mild at review. There was greater adherence to eczema management in the eczema workshop compared with the dermatologist‐led clinic. In this study, patients attending the eczema workshop had a greater improvement in eczema severity thanpatients attending a dermatologist‐led clinic, supporting collaborative models of service provision.

A pilot study to determine the short-term effects of a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial.

ABSTRACT Determining the roles of Rel/NF-κB transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor necrosis factor alpha (TNF-α)-deficient background (rela −/− c-rel −/− tnfα−/−), we show that c-rel and RelA are required for normal epidermal development. Although mutant fetuses fail to form tylotrich hair and have a thinner epidermis, mutant keratinocyte progenitors undergo terminal differentiation to form an outer cornified layer. Mutant basal keratinocytes are abnormally small, exhibit a delay in G1 progression, and fail to form keratinocyte colonies in culture. In contrast to the reduced proliferation of mutant keratinocytes during embryogenesis, skin grafting experiments revealed that the mutant epidermis develops a TNF-α-dependent hyperproliferative condition. Collectively, our findings indicate that RelA and c-rel control the development of the epidermis and associated appendages during embryogenesis and regulate epidermal homeostasis in a postnatal environment through the suppression of innate immune-mediated inflammation.