CME DERMATOLOGY Clinical Medicine 2016 Vol 16, No 1: 66–9

Atopic eczema

Author: Sara J BrownA

Atopic eczema is an itchy inflammatory skin disease with

ABSTRACT

a chronic relapsing–remitting course; it has increased in

prevalence in recent decades and now affects up to 25% of
school-aged children in the developed world and up to 10%
of adults. Recent advances in understanding the aetiology of
eczema have focused interest on skin barrier dysfunction as
a common precursor and pathological feature. In addition,
genetically determined skin barrier dysfunction (associated
with mutations in the gene encoding filaggrin) is known
to predispose to multiple systemic atopic diseases. First-
line treatments for atopic eczema focus on maintaining
and repairing the skin barrier (emollients) and reducing
inflammation (topical steroids); allergen and irritant
avoidance are also important to achieve disease control.
Second and third-line treatments include topical calcineurin
inhibitors, ultraviolet light and systemic immunosuppressant
therapies of which only ciclosporin is licenced for the
treatment of atopic eczema in adults. Novel biological
therapies are in phase II–III clinical trials.

Importance of eczema and its comorbidities

Atopic eczema (synonymous with atopic dermatitis and Fig 1. Child with moderate-severe atopic eczema. The child's upper limb
eczema1) is an itchy inflammatory skin disease which follows shows multiple areas of eczematous inflammation in flexural and non-
a chronic relapsing and remitting course. Moderate-severe flexural sites, on a background of generalised ichthyosis vulgaris (common
eczema (Fig 1) has a significant impact on the quality-of-life dry, scaly skin).
of affected patients and their close family because of itching,
scratching and sleep deprivation; the impairment in quality-of-
life is of a similar magnitude to epilepsy or type-1 diabetes in
childhood.2 In approximately 40% of cases eczema persists into
adulthood (Fig 2), having an impact on work productivity and
social functioning.3
Eczema is a complex trait, resulting from the interaction
of multiple genetic and multiple environmental factors.
Familial clustering and twin studies demonstrate that the
disease is highly heritable, emphasising the strong role of
genetic predisposition,4 while the rapid rise in prevalence of
eczema in the developed world emphasises the importance of
environmental factors.

Author: Aprofessor of molecular and genetic dermatology,

Wellcome Trust senior research fellow in clinical science and Fig 2. Adult severe atopic eczema. The skin on this adult's upper back
honorary consultant dermatologist, Skin Research Group, shows widespread erythema and scaling, indicative of active eczema, with
Ninewells Hospital and Medical School, Dundee, UK multiple excoriations.

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Up to 40% of eczema cases have atopic comorbidities

Box 1. Principles of treatment in atopic eczema.
including asthma, allergic rhinitis and type-1 hypersensitivity
to food, which may be initiated by transcutaneous > Avoid known allergens and common skin irritants (eg soap and
sensitisation.5 These comorbidities add substantially to the detergents).
disease burden. The chronic sleep disturbance resulting from > Use emollients to wash the skin with and to apply directly onto
nocturnal pruritus in eczema can lead to neurocognitive skin.
impairment. An association with neurodevelopmental
> Apply topical corticosteroid ointment (or cream when ointment
disorders, including attention deficit hyperactivity disorder, has
is not tolerated) of appropriate strength, once daily, aiming
also been observed from epidemiological studies.6
to ‘switch off’ the eczema. Then reduce potency and/or
frequency of steroid application aiming to maintain remission.
Diagnostic criteria
> Treat secondary infection, bacterial and/or viral, when this is
Eczema is diagnosed on the basis of clinical features: ill- present.
defined, erythematous, scaly and pruritic lesions with a > Topical calcineurin inhibitors can be used as second-line
clinical history characterised by childhood onset, flexural treatment for sites at high risk of corticosteroid-induced skin
inflammation (although non-flexural sites are usually involved atrophy, eg facial skin. They may also be applied once-twice
in early infancy), a background of generalised skin dryness weekly to help maintain remission.
(xerosis and/or ichthyosis vulgaris) and associated atopic
disease in the patient and/or first-degree relatives.3 Eczema > Other second- and third-line treatments include ultraviolet
can occur at any body site but in atopic patients the skin as B, ciclosporin, methotrexate (unlicensed indication) and
a whole organ shows impairment in barrier function and a azathioprine (unlicensed indication).
predisposition to inflammation, even in clinically uninflamed > Biologic agents for atopic eczema are currently in clinical trials.
sites. Barrier dysfunction also manifests as skin dryness, in part
because of increased water loss, and susceptibility to viral and
bacterial infections.
grass pollen, milk, egg and peanut. Allergens inducing a type-1
hypersensitivity reaction should clearly be avoided and there is
Principles of managing atopic eczema
some evidence that reducing dust-mite exposure in the subset
The main principles of eczema management are allergen and of sensitised patients improves eczema control.7 The most
irritant avoidance, emollient use and topical or systemic anti- common irritants encountered in everyday life are soap and
inflammatory treatment (Box 1). The most common allergens detergents; clinical experience demonstrates the utility of soap
leading to sensitisation in childhood are house-dust mite, substitutes (emollients) when bathing, but clinical trial data for
this relatively inexpensive intervention are currently lacking.8
Topical corticosteroids should be applied to areas of active
eczema at a potency aimed to induce remission, and a steroid
Key points of lower potency or less frequent application used to maintain
remission.3 Topical steroids should not be applied at the same
Atopic eczema (synonymous with atopic dermatitis and time as emollients and some specialists recommend application
eczema) is an itchy inflammatory skin disease with significant after bathing to optimise penetration through the stratum
impact on quality of life. corneum.
Second- and third-line treatments include topical calcineurin
Skin barrier dysfunction in the atopic patient facilitates inhibitors (pimecrolimus and tacrolimus), ultraviolet
allergen and irritant penetration leading to skin and systemic radiation (principally narrow-band UVB phototherapy),
inflammation, including eczema, atopic asthma, allergic rhinitis oral corticosteroids and the systemic immunosuppressants,
and peanut allergy. ciclosporin, azathioprine, methotrexate and mycophenolate
mofetil. However, ciclosporin is the only systemic
The diagnosis of atopic eczema is based on clinical history and
immunosuppressant currently licensed in the UK for adults;
examination.
systemic treatment in children is currently off licence but
ciclosporin, azathioprine and methotrexate are each used by
dermatology specialists in the UK and internationally.9,10
Treatments for eczema include allergen and irritant avoidance, Secondary infection with bacteria (most frequently
emollients, topical steroids, calcineurin inhibitors, ultraviolet Staphylococcus aureus) is very commonly associated with
radiation and systemic anti-inflammatory agents, plus the eczema exacerbations and should be treated concomitantly.
treatment of secondary infection when present. Eczema herpeticum is an infection of herpes simplex virus
within areas of skin affected by eczema; it may present as a
Urgent and emergency presentations of eczema are often medical emergency (see below).
associated with secondary infections including S aureus and A recent analysis of systematic reviews has concluded that
herpes simplex virus (as eczema herpeticum). there is a paucity of evidence for complementary eczema
treatments and non-pharmacological interventions such as
KEYWORDS: Atopic, barrier, dermatitis, eczema and filaggrin ■ specialist clothing; further well-designed clinical trials are
needed.11

© Royal College of Physicians 2016. All rights reserved. 67

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 CME Dermatology

Atopic eczema in acute medicine therapies. However, the results of a phase-II clinical trial
investigating dupilumab (a human monoclonal antibody
Patients with atopic eczema may present in the acute setting against interleukin-4 and interleukin-13) in adults with
with exacerbations of their comorbidities including asthma or moderate-severe atopic eczema are promising: 85% of patients
anaphylaxis. Acute exacerbations of eczema (so-called ‘flare- in the dupilumab group, as compared with 35% of those
ups’) are often associated with S aureus infection. Whether this in the placebo group, had a 50% reduction in the eczema
is cause or effect is uncertain,12 but eczema control requires severity score (p<0.001) after 12 weeks of monotherapy.18 A
treatment of the infection (usually with a short course of phase-IIb trial has shown a dose-dependent improvement in
oral flucloxacillin) in parallel with treatment of the atopic adults with moderate-to-severe atopic eczema;19 there were
inflammation.3 no significant safety concerns reported, although there was an
Herpes simplex virus produces a severe and potentially increased incidence of cutaneous herpes virus infections in
life-threatening infection of eczematous skin, described the dupilumab-treated group, a risk which will require further
as eczema herpeticum. This condition presents clinically assessment.
with eczema flare, pain, systemic upset and characteristic Another area of intensive research interest is the complex
monomorphic vesicular and punched-out lesions. It warrants interaction of skin and gut microbiome with cutaneous
urgent referral to a dermatology specialist for assessment and inflammation.12 These studies which have been made possible
prompt intervention with systemic antiviral therapy (acyclovir by modern sequencing technologies to circumvent the need
or valaciclovir), which may need to be given parentally, for selective bacterial cultures.20 The approach has illustrated a
with anti-staphylococcal therapy if indicated. Periorbital reduction in microbial diversity in active eczema in addition to
involvement necessitates ophthalmological review because of the well-established overgrowth of S aureus.12
the risk of corneal ulceration. Supportive treatment, including
hospital admission, intravenous fluid replacement and careful
monitoring, may be required in extensive eczema herpeticum; Conclusions and future prospects
particularly if the patient is immunosuppressed since mortality In conclusion, atopic eczema represents a complex and
may be as high as 10% in this group of patients. challenging disorder for both patient and physician.
Widespread dermatitis can contribute to the morbidity and Simple interventions, including the avoidance of allergens
mortality of multiorgan failure, therefore when present it and irritants, combined with emollient use and topical
should be treated actively. The differential diagnosis in this corticosteroids, provide the mainstay of treatment and
context includes atopic dermatitis, irritant or allergic contact are effective in the majority of cases. A subset of severe
dermatitis, stasis dermatitis and scabies infestation. recalcitrant disease necessitates systemic immunosuppression,
but more targeted and effective therapies are urgently
Advances in understanding the aetiology and required. Recent advances in understanding both genetic
pathogenesis of eczema and environmental factors in eczema pathogenesis offer
the opportunity for significant progress in this regard. The
The discovery in 2006 of loss-of-function mutations in FLG,
diverse range of phenotypes observed within the clinical
the gene encoding a skin barrier protein filaggrin13 and their
diagnosis of ‘eczema’ illustrates the need for a personalised
role in eczema predisposition14 led to a paradigm shift in
medicine approach, to target novel therapies to subsets of
understanding the pathogenesis of atopic eczema.5 This basic
patients whose disease is driven by specific pathways. The
scientific discovery has illustrated the underlying role of skin
emerging knowledge of tissue microbial diversity and its role
barrier dysfunction in the development of skin and systemic
in modulating inflammatory disease also offers opportunity
atopic diseases.4 A genetically determined filaggrin deficiency
for therapeutic manipulation of microbial communities in the
in the skin significantly increases risk of each disease in the so-
future.20 ■
called ‘atopic march’, including eczema, atopic asthma, allergic
rhinitis and peanut allergy.4,15 Skin barrier dysfunction may be
quantified in part by trans-epidermal water loss (TEWL) and Acknowledgements
increased TEWL is present as a precursor to eczema in early I am grateful to Professor Nick Reynolds and Dr Carsten Flohr for their
infancy.16 Building on this observation, recent clinical trials critical reading and comments on this manuscript. Clinical images
have produced evidence to suggest that intensive emollient are reproduced by the University of Dundee Computing and Media
use from soon after birth, aimed to enhance the skin barrier, Services, Ninewells Hospital and Medical School, with patient/parental
reduces the incidence of eczema by ∼50% in high-risk infants consent.
(defined as those with a first-degree relative having atopic
disease).17 However, the authors emphasise that larger trials are Funding
required before this approach can be recommended for routine
clinical practice. SJB is funded by a Wellcome Trust Senior Research Fellowship in
Clinical Science (ref 106865/Z/15/Z).
Despite these major advances in understanding eczema
pathogenesis, there remain considerable gaps in knowledge.
More than 30 genetic risk loci have now been identified by References
genome-wide association studies in atopic eczema but the 1 Johansson SG, Bieber T, Dahl R et al. Revised nomenclature
majority of these are in intergenic regions with unknown for allergy for global use: Report of the Nomenclature Review
function. Eczema currently lags behind psoriasis and other Committee of the World Allergy Organization, October 2003.
systemic inflammatory diseases in the availability of biological J Allergy Clin Immunol 2004;113:832–6.

68 © Royal College of Physicians 2016. All rights reserved.

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2 Beattie P, Lewis-Jones M. A comparative study of impairment of 14 Palmer CN, Irvine AD, Terron-Kwiatkowski A et al. Common loss-
quality of life in children with skin disease and children with other of-function variants of the epidermal barrier protein filaggrin are
chronic childhood diseases. Br J Dermatol 2006;155:145–51. a major predisposing factor for atopic dermatitis. Nature Genet
3 Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med 2006;38:441–6.
2005;352:2314–24. 15 Rodriguez E, Baurecht H, Herberich E et al. Meta-analysis of filag-
4 Brown SJ, McLean WH. One remarkable molecule: filag- grin polymorphisms in eczema and asthma: robust risk factors in
grin. J Invest Dermatol 2012;132:751–62. atopic disease. J Allergy Clin Immunol 2009;123:1361–70.e7.
5 Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated 16 Kelleher M, Dunn-Galvin A, Hourihane JO et al. Skin barrier dys-
with skin and allergic diseases. N Engl J Med 2011;365:1315–27. function measured by transepidermal water loss at 2 days and 2
6 Deckert S, Kopkow C, Schmitt J. Nonallergic comorbidities of months predates and predicts atopic dermatitis at 1 year. J Allergy
atopic eczema: an overview of systematic reviews. Allergy 2014; Clin Immunol 2015;135:930–5.e1.
69:37–45. 17 Simpson EL, Chalmers JR, Hanifin JM et al. Emollient enhance-
7 Nankervis H, Pynn EV, Boyle RJ et al. House dust mite reduction ment of the skin barrier from birth offers effective atopic dermatitis
and avoidance measures for treating eczema. Cochrane Database prevention. J Allergy Clin Immunol 2014;134:818–23.
Syst Rev 2015;1:CD008426. 18 Beck LA, Thaci D, Hamilton JD et al. Dupilumab treatment in
8 No authors listed. Bath emollients for atopic eczema: why use adults with moderate-to-severe atopic dermatitis. N Engl J Med
them? Drug Ther Bull 2007;45:73–5. 2014;371:130–9.
9 Proudfoot LE, Powell AM, Ayis S et al. The European TREatment 19 Thaci D, Simpson EL, Beck LA et al. Efficacy and safety of dupilumab
of severe Atopic eczema in children Taskforce (TREAT) survey. Br J in adults with moderate-to-severe atopic dermatitis inadequately
Dermatol 2013;169:901–9. controlled by topical treatments: a randomised, placebo-controlled,
10 Flohr C, Irvine AD. Systemic therapies for severe atopic dermatitis dose-ranging phase 2b trial. Lancet 2015, epub ahead of print.
in children and adults. J Allergy Clin Immunol 2013;132:774–e6. 20 Grice EA. The intersection of microbiome and host at the skin
11 Madhok V, Futamura M, Thomas KS, Barbarot S. What's new in interface: genomic- and metagenomic-based insights. Genome Res
atopic eczema? An analysis of systematic reviews published in 2012 2015;25:1514–20.
and 2013. Part 2. Treatment and prevention. Clin Exp Dermatol
2015; 40:349–54;quiz 54–5.
12 Kong HH, Oh J, Deming C, Conlan S et al. Temporal shifts in the
skin microbiome associated with disease flares and treatment in Address for correspondence: Prof SJ Brown, Skin Research
children with atopic dermatitis. Genome Res 2012;22:850–9. Group, School of Medicine, Ninewells Hospital and Medical
13 Smith FJ, Irvine AD, Terron-Kwiatkowski A et al. Loss-of-function School, Jacqui Wood Centre Level 7, James Arrott Drive,
mutations in the gene encoding filaggrin cause ichthyosis vulgaris. University of Dundee, Dundee DD1 9SY, UK.
Nat Genet 2006;38:337–42. Email: [email protected]

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