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Special Report

The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis Atopic Eczema: Who, How Frequent and Why â&#x20AC;&#x201C; Our Current Knowledge Base Standard Medical Management: Is It Enough? Prevention and NonPharmacological Treatment Therapeutic Clothing â&#x20AC;&#x201C; A Realistic Proposition?

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SPECIAL REPORT

The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

Contents

Atopic Eczema: Who, How Frequent and Why – Our Current Knowledge Base Standard Medical Management: Is It Enough? Prevention and NonPharmacological Treatment

Foreword

Therapeutic Clothing – A Realistic Proposition?

Dr R A Sykes, Editor

The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis

Dr Rupert Mason. MBBS, LRCP, MRCS. Medical Director, Espère Healthcare Ltd Sponsored by

Published by Global Business Media

Published by Global Business Media Global Business Media Limited 62 The Street Ashtead Surrey KT21 1AT United Kingdom Switchboard: +44 (0)1737 850 939 Fax: +44 (0)1737 851 952 Email: info@globalbusinessmedia.org Website: www.globalbusinessmedia.org Publisher Kevin Bell Business Development Director Marie-Anne Brooks Editor Dr R A Sykes Senior Project Manager Steve Banks

Background Therapeutic Clothing Clinical Evidence Data Assessment Their Role in Primary Care

Atopic Eczema: Who, How Frequent and Why – Our Current Knowledge Base The Prevalence of Atopic Dermatitis Aetiology of Atopic Dermatitis Current Theories – An Immunological Basis Summary

Standard Medical Management: Is It Enough?

Susan Thomas, Medical Correspondent

Production Manager Paul Davies

Moisture, Moisture, Moisture: Emollients! Flare Management The Limitations of the Reactive Model of Eczema Management Other Medical Treatments Conclusion

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Prevention and Non-Pharmacological Treatment

Advertising Executives Michael McCarthy Abigail Coombes

Dr R A Sykes, Editor

John Bushnell, Staff Writer The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated. Material in advertisements and promotional features may be considered to represent the views of the advertisers and promoters. The views and opinions expressed in this publication do not necessarily express the views of the Publishers or the Editor. While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles.

© 2013. The entire contents of this publication are protected by copyright. Full details are available from the Publishers. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical photocopying, recording or otherwise, without the prior permission of the copyright owner.

Dietary Changes – a Weak Evidence Base House Dust Mites – A Stronger Evidence Base but Difficult to Implement Clothing – A Solid and Improving Evidence Base Can We Improve Prevention? Current Theories The Future: Increasingly Individualised Care

Therapeutic Clothing – A Realistic Proposition?

Dr R A Sykes, Editor

More Than Just Rubbing You Up The Wrong Way The Financial Argument Do Any Guidelines Support Their Use? Conclusions

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

Foreword I

n this Special Report we seek to outline, in brief, our current understanding of atopic dermatitis (AD), taking particular attention to recent developments in therapeutic clothing. The overarching goal is not to force a particular agenda but at bet ter informing clinical practice by providing up to date information in a readily accessible format. We open with an interesting article outlining our current understanding of the role of therapeutic clothing in AD by Dr Rupert Mason, the Medical Director of Espère Healthcare Ltd. The Company was formed in 2006 by a group of pharmaceutical industry professionals, and working with researchers based in Europe and North America they have pioneered the development of a number of innovative solutions for the treatment of various skin and wound care related conditions, such as therapeutic clothing. The subsequent four articles then look at the problem sequentially, following a logical trail of thought. Initially the scene is set by outlining our understanding of AD with the discovery that there is an invisible inflammation and barrier defect present in the skin of patients with AD. We then review the standard medical management approach before moving on to consider the various non-medical and preventative approaches that have been used. The final article considers whether therapeutic clothing is a truly viable option, and seeks to tie together the preceding articles along these lines. A couple of facts are worthy of note before you progress onto reading the Report. Firstly, much of what is included is based on the clinical guidelines published by the National Institute for Health and

Clinical Excellence (NICE), entitled “Management of atopic eczema in children from birth up to the age of 12 years” [NICE, 2007]. Although the scope of these guidelines is limited to the under twelve year age group, the authors explain that this is based on the fact that it is in this population that most research has taken place. However, all the major UK authorities agree that they can be reasonably extrapolated to the management of older children and adults with atopic eczema. For example, although the research base is in children, an absence of research in older age groups does not indicate that interventions in older people are less effective, and indeed, there is no evidence that the pathology of the condition is any different in adulthood compared with childhood. Secondly, these guidelines are some 6 years old, and therefore omit some of the newer advances in our understanding. Where relevant this is rectified with literature searches and the inclusion of the 2012 “Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis)” by Ring et al for the European Dermatology Forum (EDF), the European Academy of Dermato-Venereology (EADV), the European Federation of Allergy (EFA), and the European Society of Pediatric Dermatology (ESPD). Over the last decade many advances have been made in the treatment of AD, and one of those that holds very real potential for benefit is therapeutic clothing (TC). It is perhaps worthy of note then, that the newer European guidelines recognise the potential for their use.

Robert Sykes Editor

Dr Robert Sykes qualified with a degree in medicine (MBChB Honours) in 2004 from the University of Liverpool where he was awarded the George Holt Medal for high academic achievement, along with commendations for a number of his clinical reviews. As a postgraduate he entered into a GP vocational training scheme before opting to work in a portfolio career, and in 2008, he set up Northern Editing (www.docrob.co.uk/nothernediting) for medical writing and editing. Currently, he is also the Executive Editor for the UK’s only peer support organisation for doctors with mental illness, the Doctors’ Support Network (registered charity 1103741; www.dsn.org.uk).

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

The Clinical Effectiveness of Therapeutic Clothing in Atopic Dermatitis Dr Rupert Mason. MBBS, LRCP, MRCS. Medical Director.Espère Healthcare Ltd Using specially designed underwear to control the symptoms of eczema is not a far-fetched dream and is supported by a strong evidence base in some cases.

Background From antimicrobial underpants to UV-filtering T shirts, clothing with a biological action is now widely available in the High Street. The technology of biofunctional textiles has also extended into medical practice particularly in the treatment of skin diseases. The management of atopic dermatitis with emollients and corticosteroids is a well established regimen but the effect of clothing on eczematous skin has hitherto been relatively unresearched. It is known that wool and synthetic polypropylene fibres can irritate atopic dermatitis1.2.3. The traditional recommendation of cotton has no evidence base and it is now known that the short stubby fibres of cotton can rub and irritate sensitive skin when moist4. It is also prone to retaining detergent after washing which then acts as an additional skin irritant5. Not before time, the past decade has seen a flurry of research investigating the interaction of eczematous skin and textiles. The result is a growing body of data on the effectiveness of therapeutic clothing in atopic dermatitis. However, before considering these data it is important

to distinguish between therapeutic clothing and retentive dressings. Retentive dressings are elasticated tubular sleeves or clothing (eg Comfifast®, Tubifast®, Skinnies®) for use with wet or dry wrapping, a technique used to control acute exacerbations of eczema. They enhance the therapeutic effect of the underlying medication by occlusion and are made from synthetic fabrics. They do not have an integral therapeutic action in their own right but are adjunctive devices used in the short term to improve the delivery of medication and help control acute inflammatory flares. As such, they are manufactured with a short duration of usage in mind, often as little as 20 washes. True therapeutic clothing for atopic dermatitis has an integral therapeutic action. It is a prophylactic therapy to be ‘applied’ or worn daily, preferably for 24 hours, and used in conjunction with other therapies such as emollients to help maintain control of the inflammatory process. It is not designed to be used for wet or dry wrapping.

Therapeutic Clothing Currently two types of therapeutic clothing have been developed for the treatment of atopic

Emollient Retentive Garments

DermaSilk

Composition

Synthetic (Rayon

Sericin-free silk

Function

Occlusive layers to enhance absorbtion

Breathable layer to control temperature and reduce itch

Usage

Short term adjunctive treatment (week)

Daily prophylactic support (months)

Life Span

Limited – 15 to 20 washes

Comparable to normal clothing

Side effects

Can cause overheating or hypothermia

None

Discontinue immediately in presence of infection

Rx Volume

6 sets to wet wrap, 3 sets to dry wrap

2-3 sets maximum

Comparative table to highlight the differences between Emollient retentive garments and DermaSilk

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

The management of atopic dermatitis with emollients and corticosteroids is a well established regimen but the effect of clothing on eczematous skin has hitherto been relatively unresearched.

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dermatitis: silver-coated materials and specialised silk fabrics. The rationale for silver-coated materials is based on the fact that colonization with S. aureus is known to be a major trigger and may also play a pathophysiological role in atopic dermatitis. The silver ions migrate from the clothing onto the skin where they suppress S. aureus colonization and toxin formation, thus minimising the inflammatory reaction. Specialised silk fabrics have a different method of action which is based partly on the natural properties of silk and partly on a few technological tweaks. Natural silk contains a protein called sericin which is a potential skin irritant. Specially treated sericin-free silk has virtually no allergenic potential and has been safely used as a suture material for decades. Clothing knitted from sericin-free silk has two key therapeutic properties. It protects the damaged skin from frictional trauma and controls its immediate environment by hydroscopically maintaining the trans-epidermal water balance thereby reducing dryness and itch6.

Clinical Evidence 1. Silver Three randomised, placebo controlled, open clinical trials have been published on the effectiveness of silver impregnated clothing (Padycare速). In a small open study Gaugher et al demonstrated a significantly greater decrease in S aureus colonisation with silver coated fabric compared to a cotton placebo7. Then in a second larger study (n=68) he demonstrated a reduction in eczema severity of 24.7% and 16.3% for silver and placebo respectively. The silver result was statistically significant compared to baseline but the placebo result failed to achieve significance. Silver also produced a greater reduction in pruritus than placebo8. Juenger et al9 recruited patients with acute inflammatory atopic dermatitis. Initially patients were randomised to either silver textile, placebo textile or corticosteroid (prednicarbate) ointment treatment. In phase two, all patients wore the silver textile. After phase one, eczema severity had improved significantly in the silver group and steroid group and during phase two healing of eczema continued in the silver group, and was observed in the silver-free group and remained at an improved level in the steroid group. Pruritus severity was significantly reduced in the silver group compared to the other two groups where improvement did not reach statistical significance. No adverse reactions were reported in these trials although the migration of silver onto the skin has raised potential safety issues in some chronic conditions where it routinely comes into contact with broken skin10.

2. Sericin-Free Silk Sericin-free silk clothing has been available on prescription in the UK since 2007. Only one sericin-free fabric is supported by productspecific published clinical data. This combines sericin-free silk with a physical antimicrobial system known as AEM 5772/5 permanently bonded to it (DermaSilk速) which destroys the cell membrane of the bacteria on contact. The antimicrobial does not migrate onto the skin and its purpose is to protect the fabric from acting as a source potentially pathogenic bacteria. There are a number of other silk based products but each one differs in construction, manufacture, additives (eg dyes) and antimicrobial agents and none of them have published efficacy data of their own. In contrast to generic medicines, there are no data establishing bioequivalence between any of these products and therefore they cannot safely be regarded as a generic group which all share the same clinical properties. The evidence base supporting sericin-free silk clothing in atopic dermatitis consists of five published clinical trials11-15. The trials were either comparative or placebo controlled and measured improvement in eczema severity using validated scoring systems such as SCORAD or EASI. In a paper published in the British Journal of Dermatology Ricci et al11 demonstrated a significant decrease in eczema severity in children (n=46) using sericin-free silk clothing compared to cotton placebo over a 7 day period. Senti et al12 conducted an open, non-randomised study with left/right intra patient comparison (n=15). Sericin-free silk was used on one side and cotton on the other. Mometasone was applied to the cotton covered limbs once daily for the first seven days and an identical base emollient was applied to both sides for the three weeks of the study. After seven days and at the end of the study evaluations of eczema severity for the two sides showed no significant difference. Koller et al13 investigated the long term effect of sericin-free silk in children (n=22) with an investigator-blinded, placebo controlled split-body study over three months. Significant reductions in SCORAD measurements were seen in the silk treated limbs compared with cotton at weeks 4, 8 and 12 confirming a prolonged and continuous effect on the treatment outcome. In another randomised double-blind trial comparing sericinfree silk with and without the AEM antimicrobial system over one month Stinco et al14 reported that eczema severity showed a constant decrease each week with the combination silk/antimicrobial fabric compared to the unmodified-silk group which showed a significant decrease only in the first 2 weeks of the study suggesting that antimicrobial addition assists in the maintenance of the long term effect.

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

effectiveness of therapeutic clothing in atopic dermatitis is significant and persuasive. The data demonstrate a beneficial effect on the control of eczema severity and the reduction of s.aureus colonisation. Specifically, sericin-free silk treated with AEM5772/5 (DermaSilk®) has been shown to be significantly superior to cotton in reducing eczema severity. The evidence database on therapeutic clothing is a work in progress, but the place of the clothing in the management of atopic dermatitis has already been accepted by the European task force on atopic dermatitis, an independent body set up by the European Academy of Dermatovenereology (EADV). In 2009 and again in 2012 the EADV guidelines recommended the prophylactic use of DermaSilk therapeutic clothing in the treatment of mild eczema16.

Their Role in Primary Care

Set of DermaSilk clothing (body suit and leggings) to suit age birth to 4 years

No adverse reactions were recorded and the absence of any chemical agents migrating onto the skin with this fabric makes any safety issues unlikely.

Data Assessment The clinical trials on therapeutic clothing in atopic dermatitis are relatively small and restricted by design limitations. The physical appearance and individual feel of the products prevent the possibility of double-blinding. The quality and size of the studies do not compare to the evidence base supporting modern systemic licensed medicines. But therapeutic clothing is a medical device, not a licensed medicine with all the safety issues of a new chemical entity. A more appropriate and useful comparison is the supportive data for topical therapies such as dressings or emollient creams and bath additives. By this yardstick the evidence for the

Many hospitals are now referring patients back to their GP with the recommendation to prescribe Therapeutic clothing. Based upon the data above and with hospital referrals costing upwards of £200 per patient, there is some logic in considering the use of Therapeutic clothing before seeking specialist advice. Whilst the garments at first glance may seem expensive, their ability to control eczema symptoms, reduce the need for costlier and labour intensive treatments, such as wrapping, coupled with their durability, make them a most cost-effective intervention in this common and time consuming condition. The aim of clinicians must be to keep eczema flares under good control and true Therapeutic Clothing has a significant role to play in reaching this goal in Primary Care.

Contact Espère Healthcare Ltd Shefford House 15 High St Shefford Bedfordshire, SG17 5DD Tel 01462346100 Fax 01462346101 Web www.dermasilk.co.uk Email info@esperehealth.co.uk

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

References 1

Diagnostic features of atopic dermatitis. Hanifin J, Rajka G Acta Derm Venereol 1980;92:44-47

Itching from wool fibres in atopic dermatitis. Bendsoe N, Bjornberg A, Asnes H Contact Dermatitis 1987;17:21-22

Factors influencing atopic dermatitis – a questionnaire survey of school children’s perceptions.

Williams J, Burr M, Williams H BJD 2004;150:1154-1161

Use of textiles in atopic dermatitis. Ricci G, Patrizi A, Bellini F Curr Problems Dermatol 2006;33:127-143

Residual washing detergent in cotton clothes: a factor of winter deterioration of dry skin in atopic dermatitis.

Kiriyama T, Sugiura H, Uehara M J Dermatol 2003;30:707-712 Use of Textiles in Atopic Dermatitis. Ricci G, Patrizi A, Bellini F et al Curr Probl Dermatol 2006;33:127-143

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Silver-coated textiles reduce staphylococcus aureus colonization in patients with atopic eczema.

Gauger A, Mempel M, Schekatz A et al Dermatology 003;207:15-21 Efficacy and functionality of silver-coated textiles in patients with atopic eczema.

Gauger A, Fischer S, Mempel M et al J Eur Acad Dermatol and Venereol 2006;20(6):534-541 Efficacy and safety of silver textile in the treatment of atopic dermatitis (AD).

Juenger M, Ladwig A, Staecker A et al Curr Med research and Opinion 2006, 22(4):739-750 Absorption of silver from dressings. Denyer J. Presentation at Wounds UK. Harrogate 2009

Clinical effectiveness of a silk fabric in the treatment of atopic dermatitis. Ricci G, Patrizi A, Bendandi B et al. Br J Dermatol 2004;150:127-131

Antimicrobial Silk Clothing in the Treatment of Atopic Dermatitis Proves Comparable to Topical Corticosteroid Treatment.

Senti, G et al Dermatology 2006; 213; 228 – 233

Action of a silk fabric treated with AEGIS™ in children with atopic dermatitis: A 3 month trial. Koller DY et al Paediatr. Allergy. Immunol. 2007 Vol 18; 4; 335-338

A Randomized Double-Blind Study to lnvestigate the Clinical Efficacy of Adding a Non-Migrating Antimicrobial to a Special Silk Fabric in the

Treatment of Atopic Dermatitis. Stinco, G et al. Dermatology 2008;21 7:191-195 Evaluation of the antimicrobial activity of a special silk textile in the treatment of atopic dermatitis. Ricci G,. et al. Dermatology 2006; 213; 224 – 227

Ring J, et al Guidelines for treatment of atopic eczema (atopic dermatitis) Part I .JEADV 2012, 26, 1045–1060

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

Atopic Eczema: Who, How Frequent and Why – Our Current Knowledge Base Dr Robert Sykes, Editor

topic Dermatitis (AD), also known as atopic eczema, or simply eczema, is a chronic, or chronically relapsing and remitting inflammatory skin disorder1,2. Clinically, it is typically intensely pruritic, and the patient’s age and the duration of the rash will influence its distribution and appearance. In infancy, it primarily involves the face, the scalp, and the extensor surfaces of the limbs but not the nappy area, whilst children and adults tend to develop it on the flexures of the limbs. Acute eczema (flares) present variously with poorly demarcated redness, vesicles, scaling, and/or crusting of the skin1. If chronic, affected skin becomes lichenified as a result of repeated scratching. The classical assessment tool is the modified “Scoring of Atopic Dermatitis” (SCORAD) developed by the European Task Force of Atopic Dermatitis (ETFAD)3,4; in general, AD with a SCORAD higher than 40 is considered to be “severe”, while AD with a SCORAD below 20 can be regarded as “mild”. However, a much more simplified approach is often applied in practice, assessing not only the physical state of the

skin but also the psychological burden as shown in Table 1.

The Prevalence of Atopic Dermatitis AD is one of the most common skin diseases, accounting for some 30% of all dermatological consultations in the UK1,5. Furthermore, although figures vary between regions, up to 20% of children, and 1-3 % of adults worldwide suffer from the condition6. In the UK, atopic eczema has a prevalence of around 15–20% of children and 2–10% of adults1. Serial surveys have shown that the prevalence of diagnosed eczema in children has trebled over the last three decades7. At the same time, GP consultation rates rose by 150% overall from 1971 to 1991, but have stabilised since7. In the majority of cases of AD (80%), the first presentation will have been before 5 years of age, with the highest peak of onset in the first year of life. It should also be mentioned that the vast majority of cases with AD can be regarded as “mild” with only 10 to 20 % of patients suffering from severe eczematous skin lesions4; although this percentage is higher in the adult

TABLE 1: Assessment of Eczema severity A good assessment of the severity of eczema is based on a thorough physical and psychological assessment. It includes: Assessing the physical impact of eczema Assessment of the skin, and self-reported itching. 1. Clear: normal skin, no evidence of active eczema. 2. Mild: areas of dry skin, infrequent itching (with or without small areas of redness). 3. Moderate: areas of dry skin, frequent itching, redness (with or without excoriation and localized skin thickening). 4. Severe: widespread areas of dry skin, incessant itching, redness (with or without excoriation, extensive skin thickening, bleeding, oozing, cracking, and alteration of pigmentation). Assessing the Psychological Impact of Eczema Assessment of how eczema affects daily activities (school, work, and social life), sleep, and mood. 1. None: no impact on quality of life. 2. Mild: little impact on everyday activities, sleep, and psychosocial well-being. 3. Moderate: moderate impact on everyday activities and psychosocial well-being, and frequently disturbed sleep. 4. Severe: severe limitation of everyday activities and psychosocial functioning, and loss of sleep every night.

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

Even in clinically unaffected skin, AD patients share common pathophysiological hallmarks and an underlying dysfunction that makes the skin more prone to irritants. The goal of future therapeutic advances may therefore lie in achieving symptom control with ever more proactive individualised therapies.

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AD population. There are no differences based on sex and ethnicity.

Aetiology of Atopic Dermatitis Aetiologically, AD has a strong genetic association. There is an 80 % concordance in monozygous twins, and a 20 % concordance in heterozygous twins1-3. Furthermore, in around 8 out of 10 children both parents are affected, and in 6 out of 10 children only one parent is affected. AD is often the first step in the development of other atopic diseases such as rhinitis and/or asthma, and it typically occurs in families with other atopic diseases (bronchial asthma and/ or allergic rhinoconjunctivitis)8. The evidence suggests that when it runs in families, the eczema also tends to be more severe, and to start earlier9. It is also known that whilst atopic eczema runs a relapsing course, there is a tendency toward gradual improvement in adult life. From an environmental perspective, AD is often made worse by, but not caused by, trigger factors, including exposure to pets, house-dust mites, pollen, as well as various food allergens (often cow’s milk or eggs) whilst breastfeeding may reduce the likelihood of getting atopic eczema in infants10. In 2011 a literature review also “revisited” the debate on the hygiene hypothesis11. After reviewing 49 studies, it found evidence to support an inverse relationship between AD and endotoxin, day care, and animal exposure in early life. Helminth infection and the consumption of unpasteurised milk was found to at least be partially protective against AD, whilst the association with viral infections was less clear due to the frequent confounding by antibiotic prescription, which was consistently associated with an increase in AD risk.

Current Theories – An Immunological Basis In the diagnoses of AD several criteria have been established12,13 without a single universally accepted, pathognomonic laboratory test. The most typical feature, the elevation of total or allergen-specific IgE levels in serum or the detection of IgE-mediated sensitization in the skin test, is not present in all individuals suffering from AD; for this latter group the term “intrinsic” (non-IgE-associated) AD has been introduced to distinguish it from “extrinsic” (IgE-associated) forms of AD14. This remains a controversial area8 with many practical implications to specific avoidance strategies in the management of this

disease. However, over the last decade several advances have been made in our understanding of the condition, above and beyond this IgEmediated theory. It has been demonstrated by various authors, for example, that even the clinically unaffected skin of atopic dermatitis patients is immunobiologially abnormal. In AD, four interrelated aspects are now believed to be disturbed. Firstly, it has been established for some time that there is an activation of the dermal venules, as well as a low-grade lymphocytic infiltration in the nonlesional skin of AD patients13. Secondly, there is a “hydrocarbon chain length deficiency” in the lipid bilayer of the stratum corneum15. In visibly healthy skin of patients with AD, long chain fatty acid length is reduced by around 50% compared to healthy controls, and in affected skin, by as much as 75%. Thirdly, there is an increased transepidermal water loss through the stratum corneum16,17,18,19 suggesting a disorder in the skin barrier function of non-lesional AD skin. Finally, the density of high-affinity immunoglobulin E (IgE) receptors on the surface of epidermal Langerhans cells is significantly upregulated in non-lesional AD skin20,21. More recently, attention has also shifted to mutations in the Filaggrin gene suggesting that these may be key organ specific factors affecting the development of eczema and other allergic conditions such as allergic rhinitis and asthma22.

Summary In conclusion, we now know that in simple terms, people with AD have a defect in the lipid barrier of the skin which leads to an increase in water loss and a tendency towards dry skin. However, how it comes about in each individual is much more complicated and is likely due to a complex interaction between susceptible genes, environmental triggers, problems with the skins barrier, and abnormal immune system responses (IgE). Whatever the precise mechanism, current theory proposes that defects in the innate immune system lead to a dysfunction in the skin’s barrier which permits an increase in allergen penetration through the epidermis, and a predisposition to secondary skin infections20. Even in clinically unaffected skin, AD patients share common pathophysiological hallmarks and an underlying dysfunction that makes the skin more prone to irritants. The goal of future therapeutic advances may therefore lie in achieving symptom control with ever more proactive individualised therapies23.

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

References 1

CKS – clinical knowledge summaries: Atopic Dermatitis. http://www.cks.nhs.uk/eczema_atopic

Ring J, et al. Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis). For the European Dermatology Forum (EDF), and the European Academy of Dermato-Venereology (EADV), and European Federation of Allergy (EFA), and the European Society of Pediatric Dermatology (ESPD).2011. http://www.turkderm.org.tr/userfiles/pdf/Guidelines%20AE%2003-05-2011%20_JR_.pdf

Kunz B, Oranje AP, Labrèze L, Stalder JF, Ring J, Taieb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1997; 195. 10-19

Wüthrich, B. (1996) Epidemiology and natural history of atopic dermatitis. Allergy and Clinical Immunology International 8(3), 77-82.

Williams HC (ed) Atopic Dermatitis. The epidemiology, causes and prevention of atopic eczema. Cambridge University Press 2000

Gupta, R. Sheikh, A. Strachan, DP. Anderson, H. Time trends in allergic disorders in the UK. Thorax. 2007 January; 62(1): 91–96.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2111268 8

Johansson SGO, et al. Revised nomenclature for allergy for global use: report of the nomenclature review committee of the world allergy organization. J Allerg Clin Immunol 2004;113:832-836

Hoare, C., Li Wan Po, A. and Williams, H. (2000) Systematic review of treatments for atopic eczema. Health Technology Assessment 4(37), 1-191. [Free Full-text]

Barnetson, R.S. and Rogers, M. (2002) Childhood atopic eczema. British Medical Journal 324(7350), 1376-1379. [Free Full-text]

Flohr C, Yeo L. Atopic dermatitis and the hygiene hypothesis revisited.Curr Probl Dermatol. 2011;41:1-34.

http://www.ncbi.nlm.nih.gov/pubmed/21576944 12 13

Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980; 92: 44-47 Mihm MC, Jr, Soter NA, Dvorak HF, Austen KF. The structure of normal skin and the morphology of atopic eczema. J Invest Dermatol. 1976;67:305–312. [PubMed] Wüthrich B, Schmid-Grendelmeier P. The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated („extrinsic“) and the nonallergic (“intrinsic“) AEDS. J

Weidinger S, O’Sullivan M, Illig T, Baurecht H, Depner M, Rodriguez E, et al. Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol. 2008;121:1203–1209. [PubMed]

Ogawa H, Yoshiike T. Atopic dermatitis: studies of skin permeability and effectiveness of topical PUVA treatment. Pediatr Dermatol. 1992;9:383–385. [PubMed]

Proksch E, Fölster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci. 2006;43:159–169. [PubMed]

Werner Y, Lindberg M. Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol. 1985;65:102–105. [PubMed]

Wollenberg A, Frank R, Kroth J, Ruzicka T. Proactive therapy of atopic eczema--an evidence-based concept with a behavioral background. J Dtsch Dermatol Ges. 2009;7:117–121. [PubMed]

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Wollenberg A, Räwer HC, Schauber J. Innate immunity in atopic dermatitis. Clin Rev Allergy Immunol.2011;41:272–281. [PubMed] Wollenberg A, Wen S, Bieber T. Phenotyping of epidermal dendritic cells: clinical applications of a flow cytometric micromethod. Cytometry. 1999;37:147–155. [PubMed

Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol. 2002;119:166–173. [PubMed]

Williams, H. Joanne R. Chalmers. Simpson, EL. Prevention of atopic dermatitis. F1000 Med Rep. 2012; 4: 24. Published online 2012 December 3. doi: 10.3410/M4-24.

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Standard Medical Management: Is It Enough? Susan Thomas, Medical Correspondent

In weekend therapy, the treatment is applied on two consecutive days, once a week, whilst twice weekly therapy advocates 1-2 days of therapy every 3–4 days. Both can be

ather than being a comprehensive review of the minutiae in the advances of the management of atopic dermatitis, this article seeks to reappraise the reader with the basic tenets of medical management. Ultimately, as every clinician will have encountered, there are cases in which this approach fails a subset of our patients and for which alternative, and innovative approaches may need to be considered. Although current research holds some hope for improvement, this article focuses on clarifying the proper use of the currently available treatments. We will therefore highlight some of the key considerations advocated by national and international agencies on the proper use of current therapies. Furthermore, there are

slight adjustments that can be made to these well-established regimes that may improve tolerability and effectiveness. The evidence in this article is taken largely from the NHS NICE guidelines of 2006/71, the major European guidelines and the CKS topic for professionals on Atopic dermatitis.

Moisture, Moisture, Moisture: Emollients! The mainstay of the medical management of atopic dermatitis can be split into prevention and flare management, and can be managed quite adequately by a general practitioner in the vast majority of cases1-3. Due to the underlying pathophysiology, emollients are essential for firstline treatment and maintenance, even when the

TABLE 2: Uses of emollients You may also be prescribed different emollients for different uses, such as:

used to prevent or treat severe eczema, especially

• an ointment when the skin is very dry • a cream or lotion when the skin is less dry • a specific one for use on your body • a different one to use on your face and hands • a lotion to use instead of soap

where there are specific patches of skin that are frequently flaring.

• a lotion to add to bath water or use in the shower

TABLE 3: How to use an emollient • Always use a large amount. MOISTURE, MOISTURE, MOISTURE! The pack inserts with most lotions give you a reasonable guide to quantity. • To avoid getting acne or “spots”: • Always smooth the emollient into the skin in the same direction that the hair grows. • Never rub the emollient in. • After a bath or shower, gently dry the skin and then immediately apply the emollient, while the skin is still moist. • Do not share emollients with other people. • Do not put your fingers into an emollient pot, but instead use a spoon or pump dispenser. This reduces the risk of spreading infection. • Normally twice a day application of the emollient is all that is necessary. • When the skin is very dry, applying the emollient every two to three hours is recommended.

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TABLE 4: How to use topical corticosteroids Apply the treatment sparingly to the affected areas. Always follow the directions on the patient information leaflet that comes with the corticosteroid. This will provide details about how much you should apply, such as the number of fingertip units. Most people only have to apply it once a day, but the most you should ever apply it is twice a day. General rules or guidelines for applying steroids: • Use the Finger Tip Unit as a guide to make sure you do not use too much (see below). • The standard length of treatment is 5-10 days. If it is used on your face or genitals, or in your armpits, it is used for only 5 days maximum. • Treatment should be continued for upto 2 days after the symptoms have settled. • Apply your emollient at a different time of the day to the topical corticosteroid. This is because the emollient will make the corticosteroid inactive or weaker. The Finger Tip Unit: How much topical corticosteroid to use Topical corticosteroids are measured in a standard unit called the fingertip unit (FTU). • One FTU is the amount of topical corticosteroid squeezed along an adult’s fingertip. • One FTU is enough to treat an area of skin twice the size of an adult’s hand.

skin is visibly clear. They are presented in three different forms: lotions, creams and ointments. The difference between them is the amount of oil and water they contain, and this in turn determines the most suitable use3. Ointments contain the most oil and are quite greasy but are the most effective at keeping moisture in the skin, whilst lotions contain the least oil so are not typically greasy, but can be less effective. Creams are an intermediate option. Emollients have a broad spectrum of uses as detailed in Table 23. However, they are frequently used incorrectly and patient education is essential, and can lead to significant improvements in symptom control2. Table 3 summarizes the guidance from NICE on how they should be used. Although they can produce acne, can be flammable4 and there is a small risk that the emollient itself may irritate the skin5, this is a relatively risk free treatment that should be used by all6. The same however is not true of the immune modulating treatments available for flare management.

Flare Management Topical corticosteroids (TCSs) are recommended for areas of eczema that are prone to inflammation1-3. However, it is well established that this should only be in the short-term, with their use being limited to flares1-3,7. It is essential that the lowest possible dose is used to control symptoms, as steroids can cause thinning of the skin (particularly in the crease of the elbow or knee joint), visible blood vessels (particularly on the cheeks), acne, and increased hair growth amongst other side effects. Table 4 details a summary of the NICE guidance on the correct

use of TCSs. Another option for flare control that have demonstrated efficacy in AD are the topical calcineurin inhibitors (TCI’s; tacrolimus and pimecrolimus). However, these are considered to be more specialized medications in the UK, and should only be initiated by doctors with a special interest and experience in dermatology8,9.

The Limitations of the Reactive Model of Eczema Management The standard medical approach to the management of eczema is therefore to provide a background treatment with an emollient in all cases, before stepping in with an appropriate level of anti-inflammatory in response to flares of the condition. Recognising the limitations of this reactive approach together with the new evidence that even healthy appearing skin has underlying pathological changes, has led to improvements in management10. Research has sought to improve symptom control, whilst simultaneously treating the underlying pathology in the skin and minimizing the side effect burden. Today, several evidence-based approaches can be implemented to these ends11,12,13,14,15,16,17. The most commonly used is the “step down approach,” which requires the patient to use the lowest amount and potency, typically of TCS, that controls their eczema10-11. However, nuanced approaches have gained popularity and favorable evidence over the last decade, focusing around intermittent therapy, with the most common being either weekend or twice weekly therapy of TCSs11-17 or TCIs15-17. In weekend therapy, the treatment is applied on two consecutive days, once a week, whilst twice weekly therapy advocates 1-2 days of therapy every 3-4 days. Both can be used to prevent or

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Innovative long-term

treat severe eczema, especially where there are specific patches of skin that are frequently flaring.

treatment strategies

Other Medical Treatments

targeting flare prevention and skin barrier stabilization are still very much needed. In order to prevent our dependence on this medical approach, with its climbing costs and side effects, the future may lie in better flare prevention.

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Antihistamines are the other major medication that most clinicians will recognize as used in AD. Although their use is common, the evidence for them is weak18. Most clinical guidelines therefore recommend that the non-sedating class are trialled, and used for short durations only1,3. The sedating antihistamines may, in some cases, have a beneficial effect where sleep is disturbed due to severe pruritus2. Moving beyond emollients, antihistamines, TCIs and TCSs are the more potent options of phototherapy and systemic immunosuppressants. Due to their potency and side effect profiles, NICE recommends that these treatments should only be offered under close supervision by specialists experienced in their use and that they should only be available “in severe cases of atopic eczema … where other management options have failed or are not appropriate, and where the atopic eczema has a significant impact on quality of life1.” Based upon this, and the cost of specialist referral and of the treatment itself, these therapies were considered beyond the scope of this article.

Conclusion Traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as TCSs and TCIs. The short term benefit of this approach is well known, but long term remission between flares remains difficult to achieve11-17. The typical medical approach over the past decade has been to focus largely upon adjusting the dosing schedule of these potent medications. In some cases, the concept of proactive therapy has been touched upon, where long-term, low-dose intermittent application of anti-inflammatory therapy to previously affected skin is used in combination with an ongoing emollient treatment to unaffected skin10. However, whilst reducing flares, this approach is not without side effects, and the authors concede this point. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are still very much needed. In order to prevent our dependence on this medical approach, with its climbing costs and side effects, the future may lie in better flare prevention, and the following article discusses this together with the various nonpharmacological methods available.

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

References 1

NICE (2007) Atopic eczema in children: management of atopic eczema in children from birth up to the age of 12 years (NICE guideline). National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text] Ring J, et al. Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis). For the European Dermatology Forum (EDF), and the European

Academy of Dermato-Venereology (EADV), and European Federation of Allergy (EFA), and the European Society of Pediatric Dermatology (ESPD).2011. http://www.turkderm.org.tr/userfiles/pdf/Guidelines%20AE%2003-05-2011%20_JR_.pdf CKS – clinical knowledge summaries: Atopic Dermatitis. http://www.cks.nhs.uk/eczema_atopic

National Patient Safety Agency (2007) Fire hazard with paraffin based skin products on dressings and clothing. Rapid response report No. 4. National Patient Safety Agency. www.npsa.nhs.uk [Free Full-text]

Danby SG, Al-Enezi T, Sultan A, Chittock J, Kennedy K, Cork MJ. The effect of aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis. Br J Dermatol. 2011;165:329–34. http://www.f1000.com/prime/717963746

Hoare, C., Li Wan Po, A. and Williams, H. (2000) Systematic review of treatments for atopic eczema. Health Technology Assessment 4(37), 1-191. [Free Full-text]

NICE (2004b) Frequency of application of topical corticosteroids for atopic eczema. Technology appraisal 81. National Institute for Health and Clinical Excellence. www.nice.org.uk [Free Full-text]

NICE (2004a) Tacrolimus and pimecrolimus for atopic eczema. Technology appraisal 82. National Institute for Health and Clinical Excellence. www. nice.org.uk [Free Full-text]

NHS. Revised guidance and competences for the provision of services using GPs with Special Interests (GPwSIs). Dermatology and skin surgery . http://www.pcc-cic.org.uk/sites/default/files/articles/attachments/revised_guidance_and_competences_for_the_provision_of_services_using_gps_with_special_interests_0.pdf

Wollenberg, A. Maximiliane Ehmann, L. Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema. .Ann Dermatol. 2012 August; 24(3): 253–260.

Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002;147:528–537. [PubMed]

G lazenburg EJ, Wolkerstorfer A, Gerretsen AL, Mulder PG, Oranje AP. Efficacy and safety of fluticasone propionate 0.005% ointment in the long-term maintenance treatment of children with atopic dermatitis: differences between boys and girls? Pediatr Allergy Immunol. 2009;20:59–66.[PubMed]

Peserico A, Städtler G, Sebastian M, Fernandez RS, Vick K, Bieber T. Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study. Br J Dermatol.2008;158:801–807. [PubMed]

Livden JK, Van Hooteghem O, Allegra F, et al. Multinational Study Group. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. BMJ. 2003;326:1367.[PMC free article] [PubMed]

Wollenberg A, Reitamo S, Girolomoni G, Lahfa M, Ruzicka T, Healy E, et al. European Tacrolimus Ointment Study Group. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy. 2008;63:742–750.

Thaçi D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, et al. European Tacrolimus Ointment Study Group. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol.2008;159:1348–1356. [PubMed]

Reitamo S, Allsopp R. Treatment with twice-weekly tacrolimus ointment in patients with moderate to severe atopic dermatitis: results from two randomized, multicentre, comparative studies. J Dermatolog Treat. 2010;21:34–44. [PubMed]

Diepgen TL. Long-term treatment with cetirizine of infants with atopic dermatitis: a multi-country, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002; 13: 278–286.

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Prevention and NonPharmacological Treatment John Bushnell, Staff Writer

Given the rising prevalence of atopic dermatitis (AD), prevention is becoming an increasingly desirable

iven the rising prevalence of atopic dermatitis (AD), prevention is becoming an increasingly desirable goal. In comparison to simply treating the consequences of the illness with potentially toxic and expensive medicines that at best only ameliorate symptoms, it could be argued that it is the best way forward for future management. AD preventative measures are not all the same however; there is of course the holy grail of the primary prevention of AD, followed by various secondary preventative measures such as the prevention of manifest atopic eczema in childhood, the prevention of severe disease and the prevention of other atopic

diseases such as hay-fever and asthma, which may follow atopic eczema. This article focuses largely on the evidence for secondary prevention, most commonly considered as lifestyle changes. The most commonly advocated of these are dietary and house dust mite (HDM) avoidance strategies, even though neither the evidence base nor the national guidelines particularly support their use. We will also briefly review the evidence for avoiding abrasive clothing, which is practicable, together with other considerations present in the literature. A summary of the typical counselling given to an AD patient can be seen in table 5.

goal. In comparison to simply treating the

TABLE 5: Counselling for AD patients can be extensive • Indoor aeroallergens

consequences of the illness with potentially

– House dust mite

• Use adequate ventilation of housing. Keep the rooms well aerated even in winter • Avoid wall to wall carpeting • Remove dust with a wet sponge • Vacuum with an adequate filtered cleaner once a week floors and upholstery • Avoid soft toys in bed (cradle), except washable ones

toxic and expensive medicines that at best only ameliorate symptoms, it could be argued that it is the best way forward for future management.

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• Wash bed sheets at a temperature higher than 55 every 10 days • Cover bedding and pillows in GoreTex or similar materials

– Pets (Furry): advise to avoid.

– Pollen: close windows in the peak season. Aeration homes at night and early in the morning or during rainy weather. Avoid exposure to lawn mowing etc.

• Food allergens: Breast feeding is recommended. Otherwise a normal diet should be followed in the absence of a proven food sensitivity • Other: Various other recommendations are frequently made, including: – Clothing: avoid skin contact with irritating fibres (wool, large fibres textiles); do not use tight and too warm clothing to avoid excessive sweating. New non-irritating clothing may be used.

– Tobacco: avoid exposure

– Maintain a “cool” ambient temperature especially in bed, and avoid excessive bed covers

– Increase the use of emollient in cold weather

– Avoid exposure to herpes sores.

– Sun exposure: no specific restriction. Usually beneficial.

– Physical exercise: no specific restrictions. Associated sweating can sometime casue AD flares. Gradually increase tolerance and duration of exercise where this occurs.

– Emotional and hormonal stress: menstruation and emotional stress have been associated with flares.

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

Dietary Changes – a Weak Evidence Base A Cochrane review involving nine randomized controlled trials (RCTs) (n = 421) has demonstrated fairly conclusively that there are no benefits for eczema when modifying the diet of people without a proven allergy1. In the presence of a proven egg allergy, children given an egg-free diet however tend to show a significantly increased reduction in the surface area of skin affected by eczema compared with children given a normal diet. Furthermore, a small RCT with 17 participants was identified and found that maternal allergen avoidance was associated with a non-significant reduction in eczema severity in breastfed infants with established AD2. Nevertheless, the study was small and compared dairy to soya exposure (which may itself be allergenic). Evidence in the absence of established allergy is then extremely weak1,3. Indeed, the evidence from RCTs in terms of “few food diets” (1 study; n=82), “elemental diets” (2 studies; n=48), “milk and egg free diets” (5 studies; n=224), where there is no proven allergy, provide clear evidence of a lack of benefit from these approaches . In addition, NICE has reported that there are no convincing benefits to be gained from the use of zinc, vitamin E supplements, or probiotic use in the management of atopic eczema.

House Dust Mites – A Stronger Evidence Base but Difficult to Implement The evidence for HDM avoidance strategies is much stronger, although it retains limitations. NICE3 for example report two randomized studies where “significant” reductions in HDM levels resulted in a reduction in the SCORAD index of individuals (HDM avoidance measures included: encasing mattresses, hot weekly washing of bed clothes, twice weekly and high-filtration vacuuming, removing soft toys, carpet spraying). However, the levels achieved in these studies are likely unachievable in everyday life, and studies where HDM levels were only moderately reduced showed no benefit4. What is more, it is increasingly being recognised that this allergen sensitisation is probably a consequence, rather than a cause of AD5,6.

Clothing – A Solid and Improving Evidence Base Clothing is an important issue in AD, not least because it spends so much time in contact with our skin. In particular, the evidenced view is that abrasive clothing should be avoided. We know that both wool and synthetic polypropylene fibres can frequently irritate atopic dermatitis7,8,9,10.

In conclusion, the evidence for most existing secondary disease prevention strategies, such as avoidance of allergens and dietary interventions, is unconvincing and inconsistent. Additionally, two RCTs suggest that rather than the actual type of fabric being important, it is the texture of the fabric itself that is the important factor11. For example, the hypothesis that cotton clothing is best for AD sufferers has largely been rebuked over the last 20 years with researchers concluding that there is nothing special about cotton for AD sufferers apart from the presence of smooth fibres, and that other synthetic fibres could be constructed using alternative yarns and fabric construction with similar benefits12,13. What is more, there is an increasing evidence base that the beneficial effect of non-abrasive clothing can be improved upon, as is the case with silver-coated textiles and sericin-free silk fabrics with the antimicrobial AEGIS finish (DermaSilk) that can reduce S. aureus colonization and eczema severity14,15,16. A detailed review of this evidence can be found elsewhere in this report.

Can We Improve Prevention? Current Theories In conclusion, the evidence for most existing secondary disease prevention strategies, such as avoidance of allergens and dietary interventions, is unconvincing and inconsistent17. Most studies in this area are generally of poor quality with numerous methodological flaws from poor concealment of randomization, to short follow up meaning that results should be interpreted with caution17,18. Fresh approaches www.primarycarereports.co.uk | 15

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to prevention therefore need to be developed and might include trying to induce tolerance to allergens in early life, as well as enhancing the defective skin barrier thereby reducing skin inflammation and sensitisation in atopy5. Early and aggressive treatment of AD represents the major secondary prevention strategy that could potentially interrupt this process. An alternative to trying to rid the environment of allergens, may in fact lie in the diametrically opposed process of attempting to induce tolerance by exposure to allergens or endotoxins at an early stage of immune development19. With regards to the former, it may be possible to learn from experiences with peanut allergy20. Equally, an option that is often overlooked, may be to actively encourage early challenge with pathogens16 where early exposure to virus, bacteria and helminth infection may confer protection against atopy. With regards to helminth infection for example, it is argued that colonization allows for the â&#x20AC;&#x153;right sort of immune stimulationâ&#x20AC;?21,22, which is supported by observations that the reintroduction of extracts from gut parasites can improve allergen tolerance23. Whilst there is now a solid evidence base for Therapeutic Clothing, further research is needed into the relative merits of other alternative non-pharmacological treatments to see whether they too offer hope for the future.

The Future: Increasingly Individualised Care The realisation that there may be a barrier defect in the skin has led some researchers to look into providing enhanced skin barrier protection rather than simply using emollients5. However, since simple emollients have been demonstrated to be just as effective as prescription barrier methods in mild to moderate disease, this may be a fruitless exercise24. Indeed, with the latest research suggesting that we should be looking at proactively maintaining the skin barrier rather chasing simple avoidance methods, and that this may actually favourably affect the clinical course of the disease, it would make little sense for a clinician to limit themselves to any one approach until the evidence better supports it. Rather, the future of prevention in AD will likely lie in a combined approach between new advances, barrier therapy and early aggressive intervention. Until the evidence base supports population level prevention, this will result in increasingly individualised therapeutic approaches to gain the maximal benefit in any given patient.

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The aim of clinicians must be to keep eczema flares under good control and true Therapeutic Clothing has a significant role to play in reaching this goal in Primary Care.

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References 1

Bath-Hextall et al. Dietary exclusions for established atopic eczema. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005203.

Kramer, Kakuma. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD000133

Bath-Hextall, F. and Williams, H. (2007) Eczema (atopic).Clinical Evidence. BM] Publishing Ltd. www.clinicalevidence.com

Williams,H. Chalmers, JR. Simpson, EL. Prevention of atopic dermatitis. F1000 Med Rep. 2012; 4: 24. Published online 2012 December 3.

Harris JM, Williams HC, et al. Early allergen exposure and atopic eczema. Br J Dermatol. 2007;156:698–704.

Williams HC. Atopic eczema – why we should look to the environment. BMJ 1995;311:1241–2.

8 9

10 11 12

Bendsoe N, Bjornberg A, Asnes H. Itching from wool fibres in atopic dermatitis. Contact Dermatitis 1987;17:21-22. Williams J, Burr M, Williams H. Factors influencing atopic dermatitis – a questionnaire survey of school children’s perceptions. BJD 2004;150:1154-1161 Use of textiles in atopic dermatitis. Ricci G, Patrizi A, Bellini F Curr Problems Dermatol 2006;33:127-143 Hoare, C., Li Wan Po, A. and Williams, H. (2000) Systematic review of treatments for atopic eczema. Health Technology Assessment 4(37), 1-191. Diepgen TL, Salzer B, Tepe A, Hornstein OP. A study of skin irritations by textiles under standardized sweating conditions in patients with atopic eczema. Melliand English 1995;12:268.

Seymour JL, Keswick BH, Hanifin JM, Jordan WP, Milligan MC. Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis. J Am Acad Dermatol 1987;17(6):988–97.

93 Gauger A, Mempel M, Schekatz A, Scha¨fer T, Ring J, Abeck D. Silvercoated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Dermatology 2003; 207: 15–21.

Ricci G, Patrizi A, Bendandi B, Menna G, Varotti E, Masi M. Clinical effectiveness of a silk fabric in the treatment of atopic dermatitis. Br J Dermatol 2004; 150: 127–131.

U Darsow. J Ring. ETFAD⁄EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. (Review for the European Task Force on Atopic Dermatitis ⁄EADV Eczema Task Force). http://www.fimp.org/dermatologia/documenti/ETFAD_EADV_2009_atopic_dermatits.pdf

Foisy M, Boyle RJ, Chalmers JR, Simpson EL, Williams HC. The prevention of eczema in infants and children: an overview of Cochrane and nonCochrane reviews. Ev-Based Child Health. 2011;6:322–39.

CKS – clinical knowledge summaries for the NHS: Atopic Dermatitis. http://www.cks.nhs.uk/eczema_atopic

Flohr C, Yeo L. Atopic dermatitis and the hygiene hypothesis revisited. Curr Probl Dermatol. 2011;41:1–34. http://www.f1000.com/prime/717963732

Du Toit G, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122:984–91. http://www.f1000.com/prime/1138943

Mpairwe H, Webb EL, et al.. Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results.Pediatr Allergy Immunol. 2011;22:305–12. http://www.f1000.com/prime/717963734

Flohr C. Williams H, et al. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam. Clin Exp Allergy. 2010;40:131–42.

Erb KJ. Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases? Trends Immunol. 2009;30:75–82. http://www.f1000.com/prime/717963735

Miller DW, et al. An over-the-counter moisturizer is as clinically effective as, and more cost-effective than, prescription barrier creams in the treatment of children with mild-to-moderate atopic dermatitis: a randomized, controlled trial. J Drugs Dermatol. 2011;10:531–7. http://www.f1000.com/prime/717963741

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Therapeutic Clothing â&#x20AC;&#x201C; A Realistic Proposition? Dr Robert Sykes, Editor

Therapeutic clothing under the brand Dermasilk is both sericin free, and AEGIS coated, in order to minimise allergenicity and maximise potential therapeutic benefits. The therapeutic benefits of silver impregnated clothing, on the other hand, are largely related to the intrinsic antimicrobial action of silver itself.

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ne of the most overlooked areas of skin care is arguably in the role of therapeutic clothing. Therapeutic clothing is not simply the avoidance of abrasive clothing, or the wearing of the traditionally recommended cotton, which itself is imperfect, but rather the use of clothing that can actually improve the outcomes of patients with atopic dermatitis (AD). As we saw in the opening article, there is a clear evidence base for its use, yet many clinicians will not be familiar with it. Moreover, this Report has reviewed the many advances that have been made over the last decade into our understanding of the aetiology and pathophysiology of AD, and we have seen how this is beginning to feedback into how we might treat the condition. We know that even in clinically unaffected skin, AD patients share common pathophysiological hallmarks and an underlying dysfunction that makes the skin more prone to both infective and allergenic irritants. Since clothing is the material with the longest and most intensive contact to human skin, it holds to reason that patients with AD should benefit from materials that either inactively or proactively reduce any potential irritation. In this final article in the series we will consider the rationale for prescribing therapeutic clothing in your practice.

More Than Just Rubbing You Up The Wrong Way As outlined elsewhere in this report, clothing plays a critical role in inflammatory dermatoses or skin conditions with an increased susceptibility to infections. Therefore, research alongside the typical treatment of AD with creams and emollients, have led to developments by the textile industry surrounding silk or silver coated textiles that may have therapeutic implications courtesy of both their antimicrobial and anti-irritant properties1. Silk has a long established history of benefit in medicine, both as a promoter of wound healing2, and as a basic suture material3. However, it is also associated with a small risk of allergenic sensitisation due to the presence of the protein sericin4. In order to combine the

Derma Silk

skin non-irritating properties of silk product with antibacterial qualities, it has been treated with AEM 5700/5772 (3-trimethylsilylpropyldimethyloctadecylammonium chloride), also called AEGIS (AEGIS Environments, Laboratory and Technical Services, MI, USA). AEGIS has demonstrable antibacterial and antifungal properties5 against many bacteria including S. aureus, doing so by destroying the pathogenic bacterial cell membrane via ion exchange, whilst at the same time appearing to spare normal skin flora. Therapeutic clothing under the brand Dermasilk is both sericin free, and AEGIS coated, in order to minimise allergenicity and maximise potential therapeutic benefits. The therapeutic benefits of silver impregnated clothing, on the other hand, are largely related to the intrinsic antimicrobial action of silver itself6. That being said, research is in keeping with the â&#x20AC;&#x153;impaired barrierâ&#x20AC;? theory of AD since wearing this clothing appears to benefit the symptomatology of AD itself, with improvements frequently seen by wearers of silver clothing6,7 .

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

A microscopic comparison to show the difference between cotton and DermaSilk

A diagram to show how DermaSilk is used in comparison with medications

Current research is suggesting that these newer fabrics may actually improve the underlying pathophysiology in AD8.

The Financial Argument There is of course a common financial argument that arises whenever new therapies come out – and it usually focuses around “that’s all very good, but it will cost too much…” Not only is the prevalence of AD on the increase9, so too is the prescribing cost10. For example, in a typical business quarter in 2008, prescribing of emollients alone represented £14.1 million, whilst corticosteroids cost £16 million11. Moreover, costs for barrier and emollient treatments rose by £4.4m (5.0%) over the 2010/11 period compared with a £9.5 million increase (7.3%) for the previous year representing both rising costs and volume. According to promotional material for Dermasilk, the NHS issues around 1200 prescriptions for Silk Garments per month with an annual cost of around £14014,15. Since many of these

prescriptions originate from secondary care, with the added cost of referral, there may be an argument for prescribing clothing earlier in order to see if benefit can be gained.

Do Any Guidelines Support Their Use? Yes , and no , but it’s not quite as simple as that! The UK guidelines for example fail to advocate the use of therapeutic clothing arguing not about the evidence for silk or silver based fabrics but the evidence for wet wrapping or bandaging; which is weak. However, the most up to date UK guidelines are those on the Clinical knowledge Summaries website (CKS) whose last major update was in 200817. The CKS guidelines are themselves based almost exclusively on the now aging 2006/7 NICE guidelines15, which themselves were based on a systematic review conducted in 200018. Therefore, the current UK guidelines fail to take into account the many advances that have taken place in our understanding and treatment of AD,

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SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

A diagrammatic representation of the mode of action of the AEM antimicrobial

being based upon data that is in the most part over a decade out of date. On the other hand, there is now recognition of the potential benefits of Dermasilk and silver clothing in the more recent 2012 European guidelines14. However, even these guidelines do not include a full review of the literature on therapeutic clothing.

Conclusions In conclusion, there is increasingly compelling evidence for the use of therapeutic clothing, especially silk based products such as Dermasilk, in the management of AD. Unfortunately, the focus in most clinical guidelines remains on the use of emollients and anti-inflammatory treatments or historically recommended non-pharmacological interventions, usually in the form of avoidance strategies. Worse still, the majority of guidelines that can be found are based on outdated research without taking a comprehensive assessment of the field. Until guidelines catch up with the evidence base, it is up to the individual clinician to make clinically driven decisions based on the rational evidence presented in the case of each and every patient. Therapeutic clothing should certainly not be offered to every patient presenting with AD, but for certain subsets of this population, particularly those with a frequently relapsing condition, it could save money and improve symptoms.

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In a typical business quarter in 2008, prescribing of emollients alone represented ÂŁ14.1 million, whilst corticosteroids cost ÂŁ16 million.

SPECIAL REPORT: THE CLINICAL EFFECTIVENESS OF THERAPEUTIC CLOTHING IN ATOPIC DERMATITIS

References 1

Haug S, et al. Coated textiles in the treatment of atopic dermatitis. Curr Probl Dermatol. 2006;33:144-51. Sugihara A, Sugiura K, Morita H et al. Promotive effects of a silk film on epidermal recovery from full-thickness skin wounds.

Exp Biol Med 2000; 225: 58–64. 3

Ratner D, Nelson BR, Johnson TM. Basic suture materials and suturing techniques. Semin Dermatol 1994; 13: 20–6.

Celedon JC, Palmer LJ, Xu X, et al. Sensitization to silk and childhood asthma in rural China. Pediatrics 2001: 107: E80.

Gettings RL, Triplett BL. A new durable antimicrobial finish for textiles. AATCC Book of Papers 1978: 259–61.

Gauger A.Curr Probl Dermatol. Silver-coated textiles in the therapy of atopic eczema. 2006;33:152-64.

Juenger M, et al Efficacy and safety of silver textile in the treatment of atopic dermatitis (AD). Curr Med research and Opinion 2006, 22(4):739-750

Fluhr JW, et al. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study. Exp Dermatol. 2010 Aug;19(8):e9-15.

Gupta, R. Sheikh, A. Strachan, DP. Anderson, H. Time trends in allergic disorders in the UK. Thorax. 2007 January; 62(1): 91–96. The Health and Social Care Information Centre, 2012. Prescriptions Dispensed in the Community: England. Statistics for 2001 to 2011. Accessed online at: https://catalogue.ic.nhs.uk/publications/prescribing/primary/pres-disp-com-eng-2001-11/pres-disp-com-eng-2001-11-rep.pdf

NHS Business Services. Prescribing Review: Drugs used for Eczema. Report dated 2008. Accessed online 16/01/2013: http://www.nhsbsa.nhs.uk/ PrescriptionServices/Documents/Prescribing_Review_Oct_-Dec_08_Drugs_used_for_Eczema.pdf

Drug Tariff Unit prices DermaSilk Body & Leggings age 2-3 years x2 and Tubifast® Body & Leggings, age 2-5 years x3 available from Espère Healthcare Ltd

http://www.medicinescomplete.com/mc/bnf/current/PHP9842-dermasilk.htm R ing J, et al. Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis). For the European Dermatology Forum (EDF), and the European Academy of Dermato-Venereology (EADV), and European Federation of Allergy (EFA), and the European Society of Pediatric Dermatology (ESPD).2011. Available at: http://www.turkderm.org.tr/userfiles/pdf/Guidelines%20AE%2003-05-2011%20_JR_.pdf

CKS – clinical knowledge summaries: Atopic Dermatitis. http://www.cks.nhs.uk/eczema_atopic NICE (2007) Atopic eczema in children: management of atopic eczema in children from birth up to the age of 12 years (NICE guideline). National Institute for Health and Clinical Excellence. www.nice.org.uk

CKS: How up to date is this evidence? http://www.cks.nhs.uk/eczema_atopic#-323396 Hoare, C., Li Wan Po, A. and Williams, H. (2000) Systematic review of treatments for atopic eczema. Health Technology Assessment 4(37), 1-191.

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