Epidemiology of eczema in South-Eastern Australia.

BACKGROUND/OBJECTIVES: Eczema is a common chronic debilitating skin condition in childhood. Data on the epidemiology and natural history of eczema across the life course are lacking. This analysis aimed to describe these epidemiological features in Australian children and adults. METHODS: Data collected on eczema from four Australian cohort studies were analysed: namely HealthNuts, Melbourne Atopic Cohort Study (MACS), Tasmanian Longitudinal Health Study (TAHS) and the Australian arm of the European Community Respiratory Health Survey (ECRHS). RESULTS: Among children aged under 6 years, 28.8%-35.6% have ever-had eczema, and 16.7%-26.6% had 'current eczema'. Among those aged 6-12 years, 14.6%-24.7% had 'current eczema' with 12.0%-18.5% of those at ages of 6 and 10 years classified as having moderate-to-severe eczema according to the Scoring of Atopic Dermatitis (SCORAD) index. In adults, the prevalence of 'eczema ever' ranged between 13.8% and 48.4%. The 12-month period prevalence of eczema was 15.1% at age 18, while current eczema was 8.5% at an average age of 51, and 8.8% at an average age 53 years. Eczema was more common among young boys, but this difference became non-significant for older children and early adolescents. In contrast, eczema was more common for adult women than men. CONCLUSIONS: Eczema is common both in children and adults. The proportion of severe eczema in children was substantial.

Low-dose rituximab and concurrent adjuvant therapy for pemphigus: Protocol and single-centre long-term review of nine patients.

Pemphigus is an autoimmune B-cell mediated blistering disease associated with significant morbidity and mortality. Rituximab has proven effective for the treatment of steroid-refractory pemphigus, although there is controversy over the optimum dosing protocol. Additionally, effective disease control often requires long-term immunosuppression, even in disease-free periods. We present a case series of a single-centre long-term follow up of nine patients with pemphigus, treated with two 500-mg doses of rituximab separated by 14 days along with concurrent adjuvant therapy. In all these patients, low-dose rituximab resulted in B-cell depletion, along with a reduction in blistering disease. Three of these patients required repeat dosing cycles due to either relapsed disease or incomplete disease control following the first dosing cycle, and have remained disease free up to 154 weeks thus far. Six patients developed minor infections during the course of their treatment, but no major complications were observed.

Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease.

Heterozygous missense mutations in the human COL7A1 gene - coding for collagen VII - lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and - together with a relatively mild phenotype - represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa. This article has an associated First Person interview with the first author of the paper.

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

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.

A low-glycemic-load diet improves symptoms in acne vulgaris patients: a randomized controlled trial.

BACKGROUND: Although the pathogenesis of acne is currently unknown, recent epidemiologic studies of non-Westernized populations suggest that dietary factors, including the glycemic load, may be involved. OBJECTIVE: The objective was to determine whether a low-glycemic-load diet improves acne lesion counts in young males. DESIGN: Forty-three male acne patients aged 15-25 y were recruited for a 12-wk, parallel design, dietary intervention incorporating investigator-blinded dermatology assessments. The experimental treatment was a low-glycemic-load diet composed 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 and severity were assessed during monthly visits, and insulin sensitivity (using the homeostasis model assessment) was measured at baseline and 12 wk. RESULTS: At 12 wk, mean (+/-SEM) total lesion counts had decreased more (P=0.03) in the low-glycemic-load group (-23.5 +/- 3.9) than in the control group (-12.0 +/- 3.5). The experimental diet also resulted in a greater reduction in weight (-2.9 +/- 0.8 compared with 0.5 +/- 0.3 kg; P<0.001) and body mass index (in kg/m(2); -0.92 +/- 0.25 compared with 0.01 +/- 0.11; P=0.001) and a greater improvement in insulin sensitivity (-0.22 +/- 0.12 compared with 0.47 +/- 0.31; P=0.026) than did the control diet. CONCLUSION: The improvement in acne and insulin sensitivity after a low-glycemic-load diet suggests that nutrition-related lifestyle factors may play a role in the pathogenesis of acne. However, further studies are needed to isolate the independent effects of weight loss and dietary intervention and to further elucidate the underlying pathophysiologic mechanisms.

The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked, controlled trial.

BACKGROUND: No previous study has sought to examine the influence of dietary composition on acne vulgaris. OBJECTIVE: We sought to compare the effect of an experimental low glycemic-load diet with a conventional high glycemic-load diet on clinical and endocrine aspects of acne vulgaris. METHODS: A total of 43 male patients with acne completed a 12-week, parallel, dietary intervention study with investigator-masked dermatology assessments. Primary outcomes measures were changes in lesion counts, sex hormone binding globulin, free androgen index, insulin-like growth factor-I, and insulin-like growth factor binding proteins. RESULTS: At 12 weeks, total lesion counts had decreased more in the experimental group (-21.9 [95% confidence interval, -26.8 to -19.0]) compared with the control group (-13.8 [-19.1 to -8.5], P = .01). The experimental diet also reduced weight (P = .001), reduced the free androgen index (P = .04), and increased insulin-like growth factor binding protein-1 (P = .001) when compared with a high glycemic-load diet. LIMITATIONS: We could not preclude the role of weight loss in the overall treatment effect. CONCLUSION: This suggests nutrition-related lifestyle factors play a role in acne pathogenesis. However, these preliminary findings should be confirmed by similar studies.

Inhibitor of Apoptosis Proteins (IAPs) Limit RIPK1-Mediated Skin Inflammation.

Inhibitor of apoptosis proteins (IAPs) are critical regulators of cell death and survival pathways. Mice lacking cIAP1 and either cIAP2 or XIAP die in utero, and myeloid lineage-specific deletion of all IAPs causes sterile inflammation, but their role in the skin is unknown. We generated epidermal-specific IAP-deficient mice and found that combined genetic deletion of cIAP1 (epidermal knockout [EKO]) in keratinocytes and ubiquitous cIAP2 deletion (cIap1EKO/EKO.cIap2-/-) caused profound skin inflammation and keratinocyte death, lethal by postpartum day 10. To investigate their role in skin homeostasis, we injected an IAP antagonist compound subcutaneously into wild-type and knockout mice. This induced a toxic epidermal necrolysis-like local inflammation, which mirrored the phenotype seen in cIap1EKO/EKO.cIap2-/- mice. Loss of one Ripk1 allele limited lesion formation and significantly extended the lifespan of cIap1EKO/EKO.cIap2-/- mice. cIAP activities are important for recruitment of LUBAC to signaling complexes, and loss of LUBAC component SHARPIN, induces dermatitis in mice. Consistent with this relationship between cIAPs and LUBAC, Ripk1 heterozygosity also protected against development of dermatitis in Sharpin-deficient mice. This work therefore refines our molecular understanding of inflammatory signaling in the skin and defines potential targets for treating skin inflammation.

Conversion of cyclosporine to tacrolimus in stable renal allograft recipients: quantification of effects on the severity of gingival enlargement and hirsutism and patient-reported outcomes.

BACKGROUND: Cyclosporine-induced side-effects such as gum enlargement and hirsutism potentially limit its effectiveness as a calcineurin-antagonist if these effects contribute to a lack of compliance. Although the differences in incidence of these effects are widely recognized, few studies are available to show the extent of reduced gum enlargement and hirsutism in patients converted from cyclosporine to tacrolimus. This study aimed to determine the efficacy and safety and patient-reported outcomes of such conversions. METHODS: Twenty-one consecutive cyclosporine-treated renal-transplant recipients with evidence of gingival enlargement were randomized into two arms: 10 continued to receive cyclosporine, 11 were converted to tacrolimus. Mean differences (0-3, 0-6, 0-9 and 0-12 months) in periodontal indices (gingival inflammation, plaque, pocket depth, gingival enlargement), hirsutism, serum creatinine and glucose and subjective differences in the patient's rating of disfigurement due to hirsutism and gingival enlargement were recorded. RESULTS: There were no differences in baseline periodontal scores between the two groups. Tacrolimus-treated subjects had significantly reduced pocket depth and gingival enlargement measures (Pocket Depths: -0.40 +/- 0.58 vs 0.30 +/- 0.35, P < 0.01; Gingival Enlargement Index: -1.12 +/- 0.83 vs-0.10 +/- 0.89, P < 0.05; tacrolimus vs cyclosporine, respectively), and decreased subjective disfigurement compared with the cyclosporine-treated group over the 12 months. While there was no difference in objective hirsutism scores between the two groups, tacrolimus-treated patients reported a significant improvement and cyclosporine-treated patients a significant worsening in their degree of disfigurement at the end of 12 months. There were no differences in creatinine or glucose levels. CONCLUSION: Conversion from cyclosporine to tacrolimus in stable renal-transplant recipients with cyclosporine-induced gingival enlargement can be achieved safely and with measurably good effect.