Docosahexaenoic acid (DHA) supplementation in atopic eczema: a randomized, double-blind, controlled trial

BACKGROUND: The increasing prevalence of atopic eczema has been linked to the alteration of the Western diet, namely the reduced consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) and an increased omega-6 (n-6) PUFA intake. OBJECTIVES: The aim of the pilot study was to determine the efficacy of dietary n-3 PUFA docosahexaenoic acid (DHA) in patients with atopic eczema. METHODS: Fifty-three patients suffering from atopic eczema aged 18-40 years were recruited into this randomized, double-blind, controlled trial and received either DHA 5.4 g daily (n = 21) or an isoenergetic control of saturated fatty acids (n = 23) for 8 weeks. At weeks 0, 4, 8 and 20 the clinical outcome was assessed by the SCORAD (severity scoring of atopic dermatitis) index. IgE production and activation of peripheral blood mononuclear cells (PBMC) were analysed. Plasma fatty acids were measured by gas chromatography. RESULTS: DHA, but not the control treatment, resulted in a significant clinical improvement of atopic eczema in terms of a decreased SCORAD [DHA: baseline 37.0 (17.9-48.0), week 8 28.5 (17.6-51.0); control: baseline 35.4 (17.2-63.0), week 8 33.4 (10.7-56.2)]. A significant reduction of anti-CD40/interleukin 4-mediated IgE synthesis of PBMC was detected in the DHA group only. Supplementation led to a modulated activation status of PBMC in both groups. The DHA group showed an increase of plasma n-3 PUFA and a decrease in the n-6/n-3 PUFA ratio. CONCLUSIONS: Our data suggest that dietary DHA could be bioactive and might have a beneficial impact on the outcome of atopic eczema, but our results need to be confirmed in a larger study.     

Levels of essential and other fatty acids in plasma and red cell phospholipids from normal controls and patients with atopic eczema.

Blood samples were collected from 48 atopic eczema patients and 33 normal subjects in Bristol, and from 434 normal individuals worldwide. In the plasma phospholipids in the atopic eczema patients, the concentrations of linoleic acid and the ratio of linoleic acid to its metabolites were significantly elevated as compared with both sets of controls. In the atopic eczema patients there were major abnormalities in the red cell phospholipids with saturated and monounsaturated fatty acids being significantly elevated and the concentrations of most essential fatty acids being significantly reduced. Patients with atopic eczema thus show abnormalities related both to desaturation of essential fatty acids and to their incorporation into red cell membranes.     

Essential-fatty-acid metabolites in plasma phospholipids in patients with ichthyosis vulgaris, acne vulgaris and psoriasis

The concentration of essential fatty acids (EFAs) and their metabolites in plasma phospholipids were measured by gas chromatography in normal individuals, and in patients with ichthyosis vulgaris, acne vulgaris or psoriasis. In all three patient groups, concentrations of arachidonic acid (20:4 omega 6) and docosapentaenoic acid (22:5 omega 6) were significantly below those in controls, suggesting that these abnormalities may occur in many skin diseases. Concentrations of dihomogammalinolenic acid (20:3 omega 6) were low in ichthyosis, normal in acne and elevated in psoriasis. Thus ichthyosis, acne and psoriasis each had a characteristic pattern of EFA metabolites.     

Biologic significance of polyunsaturated fatty acids in the skin

Deficiency of essential fatty acid (EFA) containing linoleic acid (18:2n-6) in humans or animals induces morphologic changes characterized by severe scaly dermatosis, extensive percutaneous water loss, and hyperproliferation of the epidermis. Microscopically, the epidermis is characterized by hyperkeratosis and acanthosis. The refeeding of safflower oil containing linoleic acid or primrose oil (containing linoleic acid [18:2n-6] and gamma-linolenic acid [18:3n-6]) acids to EFA-deficient guinea pigs reverses the EFA-deficiency symptoms. In contrast, replacement of safflower oil with menhaden fish oil, (containing eicosapentaenoic acid [20:5n-3] and docosahexaenoic acid [22:6n-3]) did not reverse the symptoms of EFA deficiency. These results indicate: (1) that an understanding of the roles of vegetable or fish oil in skin must evolve from an understanding of the roles of each constituent n-6 or n-3 fatty acid, and (2) that the n-3 fatty acids may function to modulate the metabolism and function of the n-6 fatty acids in vivo.     

Induction of epidermal hyperproliferation by topical n-3 polyunsaturated fatty acids on guinea pig skin linked to decreased levels of 13-hydroxyoctadecadienoic acid (13-hode)

Reversal of essential fatty acid deficiency (EFA) induced epidermal hyperproliferation was recently suggested to require linoleic acid and an active lipoxygenase product. Because the nature of this lipoxygenase product is unknown, we employed a model of n-3 polyunsaturated fatty acid (PUFA) induced hyperproliferation in guinea pig skin to test a possible reversal of the hyperproliferation by an oxidative metabolite of linoleic acid. Topical applications of two n-3 PUFA: 0.5% of eicosapentaenoic acid (20:5n-3) and/or of docosahexaenoic acid (22:6n-3) for 5 d induced severe epidermal hyperproliferation. Development of the epidermal hyperproliferation paralleled a marked decrease in the major epidermal linoleic acid lipoxygenase product (13-hydroxyoctadecadienoic acid; 13-HODE). The application of 0.1% of 13-HODE to the n-3 PUFA-induced guinea pig hyperproliferative skin resulted in the restoration of normal epidermal histology and reversal of hyperproliferation as determined by epidermal uptake of 3H-thymidine. These data support the view that 13-HODE may represent the endogenous cutaneous mediator necessary for full restoration of cutaneous symptoms of essential fatty acid deficiency. Furthermore, the topical use of n-3 PUFA for the disruption of normal metabolism of skin n-6 EFA (linoleic acid) does serve as a useful tool for further investigations into the regulatory mechanisms of in vivo epidermal proliferation/differentiation.     

(14) Essential fatty acids and the skin

Experimental studies in animals have highlighted the importance of essential fatty acids (EFAs) in normal epidermal structure and function, and hair growth. Recent work on EFA metabolism in man has identified certain specific abnormalities in atopic eczema¹, and psoriasis, acne vulgaris and ichthyosis (unpublished observations). Dietary supplements have been shown to correct the EFA deficiency in atopic eczema and also to ameliorate the clinical disorder. We present a pictorial review of the evidence relating EFA metabolism to disorders of the skin, nomenclature of the EFA series, the main dietary sources of EFAs and the range of commercially available dietary supplements.     

n-6必需脂肪酸与特应性皮炎研究进展

n-6必需脂肪酸代谢的异常在特应性皮炎(AD)发病机理中起着重要的作用,脂肪酸的减少可以导致抗炎作用的减弱及皮肤屏障功能异常,通过补充n-6脂肪酸可以明显改善AD患者的症状,早期采用n-6脂肪酸来进行主动干预有希望预防AD的发生与发展。     

Human essential fatty acid deficiency: treatment by topical application of linoleic acid.

An essential fatty acid (EFA) deficiency developed in a 19-year-old man who was being maintained on a long-term regimen of fat-free, intravenous hyperalimentation fluids. The EFA deficiency was reversed after 21 days by daily, topical application of linoleic acid to the patient's skin. The ratio of eicosatrienoic acid (20:3, n-9) to eicosatetraenoic acid (20:4, n-6) decreased to normal levels in the skin and serum with clinical improvement of the EFA deficiency syndrome. The cutaneous manifestations (scalp dermatitis, alopecia, and depigmentation of hair) were reversed with continued, topical application of safflower oil, which contains 60% to 70% linoleic acid.     

Abnormal essential fatty acid metabolism in Darier's disease

Fatty acid levels in plasma and erythrocyte cell membranes were determined in 13 Danish patients with Darier's disease and 21 Danish controls. Concentrations of the main dietary essential fatty acids, linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), were consistently modestly above normal; concentrations of the delta 6-desaturase metabolites of both linoleic and alpha-linolenic acids, however, were consistently and often significantly below normal. These results suggest that the capacity of the enzyme delta 6-desaturase activity is inadequate in patients with Darier's disease.     

Implications of dietary oils and polyunsaturated fatty acids in the management of cutaneous disorders

A major proinflammatory metabolite of arachidonic acid, leukotriene B4, is known to accumulate in the lesions of psoriasis. Most of this metabolite is biosynthesized by the polymorphonuclear cells that infiltrate into the psoriatic lesions. Epidermal 15-lipoxygenase, on the other hand, metabolizes arachidonic acid into 15-hydroxyeicosatetraenoic acid (15-20:4n-6), presumably serving as a negative feedback to inhibit the local generation of leukotriene B4. Eicosapentaenoic acid, a major polyunsaturated fatty acid in fish oil, and gamma-linolenic acid, a poly-unsaturated fatty acid in certain vegetable oils, are both metabolized by epidermal 15-lipoxygenase into 15-hydroxyeicosapentaenoic acid (15-OH-20:5n-3) and 15-hydroxyeicosatriaenoic acid (15-OH-20:3n-3), respectively. Both of these monohydroxy acids are potent in vitro inhibitors of leukotriene B4 generation. It seems reasonable, therefore, that adequate dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid may offer a novel and nontoxic approach to suppressing cutaneous inflammatory disorders.     

Immunological Studies of herpes simplex virus infection in children with atopic eczema

Summary This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (>3) to HSV antigen, and high HSV lgG antibody titres measured by ELISA. Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Imairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.     

Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema

The non-involved skin of atopic eczema (NEAE) is characterized by severe dryness and an impaired barrier function of the stratum corneum as indicated by an increased transepidermal water loss. Previous studies have demonstrated that this barrier impairment coincides with marked alterations in the amount and composition of stratum corneum ceramides. The aim of this study was to identify specific alterations in NEAE that may be used in the diagnosis of the atopic eczema. Using a classical procedure for high performance thin layer chromatography we could confirm earlier results: apart from Cer(EOH), which contains omega-hydroxy fatty acid (O) ester-linked to linoleic acid (E) and amide-linked to 6-hydroxy-4-sphingenine (H), the quantities of all ceramide fractions were significantly decreased. Furthermore, Cer(EOH)/Certotal was significantly increased, whereas the percentage of Cer(EOS), which contains sphingosine (S), and Cer(NP), which contains non-hydroxy fatty acid (N) amide-linked to phytosphingosine (P), were significantly decreased. Using a modified procedure for high performance thin layer chromatography we could demonstrate the formation of a double peak in the position of Cer(AS), which contains alpha-hydroxy fatty acid (A), in lipids of NEAE. The subfractions of the double peak comprised 15% and 12% of Certotal. MALDITOF mass spectrometry suggested that the double peak was formed by a homologous series of mono-hydroxylated and mono-unsaturated ceramides of different chain length, e.g., Cer(AS) subfractions containing either (C16,18) or (C22,24,26) alpha-hydroxy fatty acids. In contrast, in normal skin a single peak in Cer(AS) position, which comprised 22% of Certotal, was mainly formed by the long chain subfraction. In some cases this single peak displayed a small shoulder at its right flank, but never showed a clear peak separation when developed with NEAE samples. Furthermore, even in senile xerosis, or in either non-involved skin of psoriasis or seborrhoic eczema, only a single peak occurred in Cer(AS) position. Accordingly, the double peak might be specific for NEAE and turn out to be a marker for atopic eczema.     

Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients

BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a skin disease similar to atopic eczema and its associated dry skin and itching. METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40 patients with asteatotic eczema. Efficacy was assessed by eczema area and severity index (EASI), investigators global assessment (IGA), patient's self-assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the primary efficacy variable, was reduced by 62+/-7% from baseline in patients on pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With pimecrolimus there was also a better control of pruritus (P=0.042) at week 4 whereas a better control of disease according to self-assessment could only be observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream 1% is effective in patients with asteatotic eczema.     

The Effect of Environmentally Friendly Wallpaper and Flooring Material on Indoor Air Quality and Atopic Dermatitis: A Pilot Study

Background

Formaldehyde (FA) and other volatile organic compounds (VOCs) are considered among the main causes of atopic aggravation. Their main sources include wallpapers, paints, adhesives, and flooring materials.

Objective

To assess the effects of environmentally friendly wallpaper and flooring material on indoor air quality and atopic dermatitis severity.

Methods

Thirty patients with atopic dermatitis were enrolled in this study. To improve air quality, the wallpaper and flooring in the homes of the subjects were replaced with plant- or silica-based materials. The indoor air concentration of FA and the total VOCs (TVOCs) were measured before remodeling and 2, 6, and 10 weeks thereafter. Pruritus and the severity of atopic eczema were evaluated by using a questionnaire and the eczema area and severity index (EASI) score before and at 4, 8, and 12 weeks after remodeling. The subjects were instructed to continue their therapy for atopic dermatitis.

Results

The houses of 24 subjects were remodeled; all subjects completed the study. The concentration of FA in ambient air significantly decreased within 2 weeks after remodeling. The TVOC level showed a decrease at week 2 but increased again at weeks 6 and 10. The reduction of pruritus and EASI score was statistically significant in patients whose baseline EASI score was >3.

Conclusion

Replacing the wallpaper and flooring of houses with environmentally friendly material reduced FA in ambient air and improved pruritus and the severity of atopic eczema. The improvement of pruritus and eczema was statistically significant in patients whose baseline EASI score was >3.     

Infant feeding and the development of food allergies and atopic eczema: An update

There is an increasing awareness of food allergies in the community. Dermatologists frequently see patients with atopic eczema, where parents are extremely concerned about the role of food allergy. Advice given to parents regarding the timing of introduction of solid foods has changed markedly over the past decade. Whereas previous advice advocated delaying the introduction of solid foods until the infant's gastrointestinal system had matured, recent studies suggest that the introduction of solids from around 4 to 6 months may actually prevent the development of allergies. Studies on maternal dietary restrictions during pregnancy and lactation have led researchers to believe that antigen avoidance does not play a significant role in the prevention of atopic disease. Breastfeeding exclusively for 4 to 6 months has multiple benefits for mother and child, however, it does not convincingly prevent food allergies or decrease atopic eczema. New evidence suggests that the use of hydrolysed formulas does not delay or prevent atopic eczema or food allergy. This article aims to highlight current evidence and provide an update for dermatologists on the role of food exposure in the development of atopic disease, namely atopic eczema.     

Stigmata of atopic constitution in patients with atopic eczema or atopic respiratory disease.

In the diagnosis of atopic eczema, minor physical markers (stigmata) frequently provide valuable clues. The prevalence of nine stigmata (dry skin, hyperlinearity of the palms or soles, infraorbital fold, white dermographism, facial pallor, orbital darkening, Hertoghe's sign, low hairline) was evaluated in 34 atopic eczema patients without atopic respiratory disease, in 16 patients with allergic rhinitis and/or asthma without atopic eczema, and in 23 controls without atopic respiratory or eczematous disease, and with negative results at prick testing with three common aeroallergens. Compared with controls, all features except Hertoghe's sign were significantly (p less than 0.01) more frequent in atopic eczema, and, except for Hertoghe's sign, dry skin and white dermographism, they were significantly (low hairline, p less than 0.05; others, p less than 0.01) more frequent also in respiratory disease. The prevalence of most stigmata did not differ significantly (p greater than 0.05) in cutaneous vs. respiratory atopic disease, only dry skin being more frequent in atopic eczema (p less than 0.05). Although not specific, most stigmata are characteristic markers not only of atopic eczema, but of atopy as such.     

Atopic background in patients with occupational hand eczema

Of 368 patients with hand eczema examined during the years 1978-79, at a Department of Occupational Dermatology, 39% had a history of atopic disease (dermatitis, asthma, or rhinitis). 28% of the patients had or had had atopic dermatitis. The % of atopics in the patient material was highest in the age range 20-24 years, in which 57% of the patients had a history of atopic dermatitis, compared with only 11% in the age range above 35 years. Of all patients with a history of atopy, 22% had developed allergic contact dermatitis, while the corresponding figure for non-atopics was 45% (p less than = 0.001). Positive patch test reactions occurred in a significantly smaller number of individuals with past or present atopic disease than in non-atopics. Atopics had not changed jobs because of hand eczema to a greater extent, but had healed to a lesser extent after change of occupation than non-atopics (p less than 0.01).     

In vitro model of essential fatty acid deficiency.

The polyunsaturated fatty acids linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) are essential for normal skin function and structure, both as eicosanoid precursors and as components of lipids forming cell membranes. Adult human keratinocytes grow optimally in serum-free medium (MCDB 153) that contains no fatty acids. These keratinocytes expand rapidly and produce normal epidermis upon in vivo grafting. Analysis of lipid extracts of epidermis and of cultured keratinocytes was done to determine the fatty acid composition of cells grown in essential fatty acid (EFA)-deficient medium. Gas chromatography and high-performance liquid chromatography analyses were done of the fatty acids in the entire cell and in a thin-layer chromatography separated fraction containing those lipids that form cellular membranes. Comparison of snap-frozen epidermis and epidermal basal cell suspensions to passage 1 to 4 cultures shows that the cells are in an extreme essential fatty acid-deficient state by the first passage. The amount of the saturated fatty acids 16:0, 18:0, and 14:0 is unchanged by culture. The polyunsaturated fatty acids are found to be significantly decreased, the cells balancing their lack with a significant increase in the relative abundance of the monounsaturated fatty acids, 18:1 and 16:1. Greater than 85-90% of the fatty acids was found in lipids associated with membranes and no unusual fatty acids were detected. Because the serum-free medium is fatty acid free and the cells cannot synthesize essential fatty acids, the rapid division of the cells results in the predominance of an extreme EFA-deficient cell type. The essential fatty acid-deficient keratinocyte is an excellent adult, normal epidermal cell model that can be used to study EFA deficiency and the effect of the eicosanoid and fatty acids on cell function and structure.     

Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse

BACKGROUND: The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome. OBJECTIVES: To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema. METHODS: Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent. RESULTS: At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42.9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used. CONCLUSIONS: This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.     

Serum antibody to staphylococcal teichoic acid and α-haemolysin in dermatological patients

Teichoic acid antibody (TAA) titres and antibody to α-haemolysin of Staphylococcus aureus (ASta) were measured in 274 dermatological patients and 200 normal controls. Positive Asta values (≥2.0 iu/ml) were common in patients with chronic pruritic dermatoses such as atopic dermatitis (44% ASta positive) and infective eczema (28% ASta positive), but patients with primary pyoderma were all ASta negative. Positive TAA titres (≥1:4) were seen less frequently than positive ASta values, but still significantly more often in atopic dermatitis patients than in controls. Routine skin swabs were taken from all patients, but positive TAA or ASta tests correlated neither with growth of Staphylococcus aureus from skin lesions nor with signs of clinical infection. This study shows that the TAA test cannot be used as an indicator of septic staphylococcal infection in patients with atopic dermatitis.