Clinical Review - Atopic eczema

Contributed by Dr Rufaro Gamanya, clinical lecturer, department of dermatology and wound healing, Cardiff University School of Medicine.

Flexural involvement in the childhood phases of AE. Note accentuation of skin markings (lichenification0 and excoriations (right)
Flexural involvement in the childhood phases of AE. Note accentuation of skin markings (lichenification0 and excoriations (right)

Section 1: Epidemiology and aetiology
Atopic eczema (AE) is a chronic relapsing disease of the skin characterised by dry itchy eczematous lesions. The lifetime prevalence of AE is estimated to be between 15 and 30% in children and 2 to 1% in adults.1,2 50% of childhood AE occurs before the age of one and 85% before the age of five.3

Breakdown in skin barrier function is the primary event in the development of AE. The skin barrier, the stratum corneum, is made up of corneocytes surrounded by a lipid lamellar matrix which prevents water loss. Corneocytes contain natural moisturising factor (NMF) with humectants, such as urea. Humectants are substances which retain water and therefore reduce transepidermal water loss (TEWL) while maintaining the skin pH at 5.5.1

NMF is produced by breakdown of filaggrin, a stratum corneum protein. Changes in water content of the stratum corneum trigger filaggrin degradation.4 Corneocytes are held together by corneodesmosomes. Protease enzymes break down corneodesmosomes during desquamation and their activity determines the thickness of the barrier.1

Genetic factors
Mutations in the gene encoding filaggrin predispose to AE.1 In the UK up to 50% of patients with AE are heterozygous for one of the mutations.5 Reduced levels of filaggrin result in reduced NMF and decreased ability of corneocytes to retain water. Reduced NMF raises the skin pH which increases protease activity. Furthermore, mutations in protease enzyme genes induce excessive protease activity leading to a thin stratum corneum susceptible to penetration of irritants.1

Deficiency in genetic expression of antimicrobial peptides (B-defensins and cathelicidin) in AE accounts for increased susceptibility to cutaneous infections especially Staphylococcus aureus.2 Staph aureus toxins act as superantigens stimulating inflammatory response and damage to the skin barrier.6

Familial predisposition to increased serum IgE antibodies and sensitisation to various allergens is seen in AE. Defective cell-mediated immunity is also responsible for predisposition to AE and cutaneous infections.

Environmental factors
Surfactants, such as soap and detergents, emulsify skin lipids, reduce corneocyte water retention and increase TEWL.1 Surfactants further disrupt the barrier by increasing skin pH thus enhancing protease activity and inhibiting lipid synthesis.

House dust mite proteins induce IgE-mediated responses and have direct proteolytic activity which triggers inflammation.1 Exposure to aeroallergens and sensitisation to food allergens has been shown to increase risk and severity of AE.3

The complex interplay between genetic and environmental factors results in a defective skin barrier susceptible to allergen and microbial penetration. The release of inflammatory cytokines triggers itching and a vicious itch-scratch-itch cycle commences with further skin barrier damage (Click here to see aetiology of AE summary chart).

Section 2: Making the diagnosis
The diagnosis of AE is made clinically. A detailed clinical history should include family history of atopy, exacerbating factors and impact on quality of life. The UK Working Party Diagnostic Criteria for AE is easy to use and has been extensively validated (see table below).

Diagnostic Criteria

History of an itchy skin condition plus three or more of the following:

  • History of a rash in the skin folds.
  • Visible flexural dermatitis.
  • History of asthma or hayfever.
  • History of a generalised dry skin in the past year.
  • Onset of rash under the age of two years.

Presentation
AE is an episodic disease punctuated by flares and remissions, hence the clinical presentation may be quite varied. The eczematous lesions may be acute with intense erythema, exudation and blistering, sub-acute with thick and excoriated plaques or chronic with accentuated skin markings due to repeated scratching and rubbing of the skin (lichenification) and pigmentary changes.2

Most patients have dryness (xerosis) of the skin even during remissions. Intense itching is the diagnostic hallmark of the disease and is the most debilitating symptom.

The clinical picture of AE varies with age and three phases can be discerned. The infantile phase up to two years of age typically involves the face, the trunk and extensor aspect of the limbs, with sparing of the nappy area.2 In the childhood phase, between two and 12 years of age, the typical pattern involving flexural sites is seen.

In the adolescent or adult phase the lesions are similar to the childhood phase but with frequent involvement of the head, neck and hands. Often adults develop a prurigo type of AE with predominant excoriated nodular lesions. Assessment of severity should include extent of skin involvement, degree of inflammation and the impact on quality of life.

Secondary bacterial and viral infections, which are common, may modify the clinical picture. Staphylococcal impetiginisation of the eczematous lesions leads to yellow impetigo-like crusting and weeping. Bacterial cultures are of little value due to the high prevalence of colonisation of AE skin by Staph aureus. However, in cases of recurrent or frequent, severe or recalcitrant infections, swabs for bacterial culture to exclude MRSA or other pathogens are indicated. Patients are at risk of widespread infection with herpes simplex (eczema herpeticum) and clinically this presents as sudden worsening eczema with punched out vesicles at the same stage of development.

Important differential diagnosis includes other types of eczema especially in adults in whom there may be coexisting elements of contact and irritant eczema. Psoriasis and dermatophyte infections are important differentials to consider, particularly where the disease affects the hands and feet. Scabies should also be considered.

Allergy testing in AE is controversial due to the multifactorial nature of the disease. There is no evidence to support the use of any particular diet for patients with AE.

Section 3: Managing the condition
The primary treatment aims are to improve skin barrier function, suppress inflammation and control infection.

Maintenance of skin barrier
Emollient therapy tailored to the needs of the patient must be used at all times. Bath additives and soap substitutes should replace irritant detergents, such as soaps, shower gels and bubble baths. Bathing once a day and not for longer than 20 minutes reduces waterlogging, which weakens the lipid layer and increases skin permeability, leading to dryness.7

Leave-on emollients are applied at least twice a day using downward strokes in the direction of hair growth to minimise risk of folliculitis. Sufficient quantities should be prescribed (adults: 600g and children: 250g per week). Intervals of 30 minutes of applying emollient before topical anti-inflammatories are applied reduce dilution and possible interference with stability and absorption of medication.7

In very dry skin and when itching is a problem, emollients can be applied under occlusive bandages. Bandages should not be used in clinical signs of infection.

Anti-inflammatory therapy
Topical corticosteroids are the first-line treatment. Their potency is tailored to AE severity, body site and age of patient.

During flares, a step-up approach is used in which a moderate to high potency preparation is used once or twice daily followed by a dose reduction or a low potency preparation gradually to reduce withdrawal rebound.

For facial and intertriginous skin flares, mild to moderately potent steroids may be used for periods of up to 14 days; less potent steroids, such as hydrocortisone, should be used in children.2

Topical calcineurin inhibitors (TCIs), pimecrolimus and tacrolimus are recommended second-line treatments in patients over the age of two years. Tacrolimus is effective for short and intermittent treatment of AE.8

TCIs do not induce skin atrophy, which favours their use over steroids in delicate sites. Close monitoring of patients on anti-inflammatories is essential.

Antimicrobial therapy
Risk of antibiotic resistance makes eradication of Staph aureus an inappropriate long-term strategy. However, overgrowth of Staph aureus can cause exacerbation of AE and antistaphylococcal therapy may be indicated in poorly controlled disease.6

A combined topical steroid and antibiotic regimen for up to two weeks, including antiseptics (triclosan and chlorhexidine), with a low sensitising potential may be useful.3 Clinical signs of bacterial infection justify treatment with systemic antibiotics.

Sedative antihistamines may be useful in the short term, during relapses associated with severe pruritus or urticaria, in patients over the age of six months. Ongoing patient education regarding prevention of aggravating factors, including appropriate clothing and cool temperature at night-time is important. Patients should also be educated about early identification of flares and correct topical treatment application. Awareness of the causes of treatment failure and the indications for early referral to secondary care are essential.

Section 4: Prognosis
The natural history of AE involves relapses and remissions with a variable prognosis. The skin barrier function improves naturally with age and in 63% of children who develop AE in the first two years of life, it resolves by the age of three and only 20% will have persisting disease by the age of seven.1,3

Disease persistence
Patients with early-onset AE and filaggrin mutations tend to have persistent disease into adulthood.

Other risk factors for disease persistence and severity include family history of atopy, head and neck involvement, dry/itchy skin in adult life, widespread eczema in childhood, female sex and associated allergic rhinitis and asthma.3,9,10

AE is a major risk factor for developing asthma. Around 70% of patients with severe AE develop asthma, compared with 8% of the general population.11

Children with severe AE requiring frequent use of higher potency topical steroids are at risk of systemic side-effects, such as growth retardation from hypothalamic-pituitary axis suppression, posterior subcapsular cataracts and glaucoma.

Subcapsular cataracts
AE itself is associated with anterior and posterior subcapsular cataracts with prevalence ranging from 1 to 25%.12 The cause of the cataracts is unknown, however, it has been suggested that habitual rubbing of the face may play a part.13

Patients applying topical corticosteroids to the eyelids for over four weeks should undergo intra-ocular pressure measurements, and if possible, be prescribed TCIs instead.12

There have been reports of association of AE and an increased risk of lymphoma; however, further investigation to clearly establish this link is required.13

Section 5: Case study
A four-year-old boy was referred with an eight-month history of poorly controlled eczema.

He had recurrent episodes of infection requiring repeated courses of antibiotics. He had a history of AE from the age of six months. His sleep was disturbed and he often woke with blood on his pyjamas.

His mother was concerned about side-effects of topical steroids so she had been applying the treatment less often, sparingly and only to very red areas on his legs.

Apart from the mild topical steroid, his other treatment consisted of an emollient as a soap substitute and an ointment used twice a day. His mother noted that the ointment made his skin itchier so he sometimes refused to use it.

He had no known allergies and mild hayfever. His sister and father both had asthma.

Examination
Examination revealed dry skin with ill-defined erythema and excoriations on his legs. There was crusting over the popliteal and antecubital fossae with lichenification on both wrists and ankles. Dry erythematous skin over the trunk and neck was noted. He was scratching throughout the consultation.

A diagnosis of moderate to severe AE with secondary infection was made. Bacterial swabs were taken from the crusted sites in view of the history of recurrent infections. Allergy testing is not routinely carried out, unless indicated.

Targeted treatment to address xerosis, inflammation, infection and itching was commenced. This consisted of an emollient with antiseptic and antipruritic properties as a bath additive and soap substitute; a leave-on emollient to be used at least three times a day; a systemic antistaphylococcal anti-biotic for seven days; a moderately potent steroid cream and a sedating antihistamine at night for 14 days.

Time was spent with the specialist nurse on education and counselling to raise the mother's awareness of potential aggravating factors.

Correct application of emollients and topical steroid was demonstrated.

The mother's concerns regarding topical steroids were addressed and a decision was made to consider introducing tacrolimus at follow-up if frequent topical steroids were required. At the three-week follow-up there was significant improvement with no evidence of infection and minimal excoriations. The skin was still very dry so an ointment was added to the treatment regimen.

Section 6: Evidence base

Clinical trials

Gene-environment interaction and effect on epidermal barrier and development of AE is explored in detail.

  • Schmitt J, von Kobyletzki L, Svensson A et al. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol 2011; 164: 415-28.

The role of 'proactive' treatment with low-dose anti-inflammatories to reduce/prevent flares is explored in this systematic review of randomised controlled proactive treatments.

Limitations of currently available treatments for AE, advantages and disadvantages of new therapeutic modalities and potential new cellular targets are discussed.

  • Greer FR, Sicherer SH, Wesley Burks A. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008; 121(1): 183-91.

This report reviews the evidence relating to the role of diet in AE. There is evidence that exclusive breastfeeding in the first four months of life in infants at high risk of developing atopy may decrease the risk of developing atopic dermatitis in the first two years.

Guidelines

  • NICE. Atopic eczema in children: management of atopic eczema in children from birth up to the age of 12 years. CG57. London, NICE, 2007.

Refer to table 1 on assessment of disease and table 2 on stepped approach to management.

An extensive guideline, covering all the salient points relating to the management of AE.

Key text

  • Williams H. Evidence based dermatology (second edition). Oxford, Blackwell Publishing, 2008.

The chapter on atopic dermatitis is well written and concise. Case scenarios and questions are used as triggers to discuss the evidence-based management of eczema.

Online

The 'What's New' section provides annual evidence update information.

This is a good resource for clinical guidelines.

Visit MIMS Learning for an updated version of this article

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Consolidate your learning by inviting a dermatologist to your practice to discuss how to manage difficult cases of AE.
  • Set up an eczema clinic, auditing the outcomes and referral rates to secondary care.
  • Produce a leaflet on eczema, highlighting the importance of preventive measures, regular use of emollients and when to seek medical advice.

References
1. Cork MJ, Danby SG, Vasilopoulos Y et al. J Invest Dermatol 2009; 129: 1892-1908.

2. Bieber T. Ann Dermatol 2010; 22(2): 125-37.

3. Akdis CA, Akdis M, Bieber T et al. Allergy 2006; 61: 969-87.

4. Sandilands A, Sutherland C, Irvine AD et al. J Cell Sci 2009; 122(9): 1285-94.

5. Flohr C, England K, Radulovic S et al. Br J Dermatol 2010; 163: 1333-6.

6. Leung DYM. Curr Opin Pediatr 2003; 15: 399-404.

7. Peters J. Br J Comm Nurs 2001; 6(12): 645-51.

8. Baldo A, Cafiero M, Caterino P et al. Clin Cosmet Investig Dermatol 2009; 2: 1-7.

9. Rance F, Boguniewicz M, Lau S et al. Pediatr Allergy Immunol 2008; 19 (suppl 19): 17-25.

10. Sandstrom MH, Faergemann J. Br J Dermatol 2004; 150: 103-10.

11. Zheng T, Jinho Y, Oh MH et al. Allergy Asthma Immunol Res 2011; 3(2): 67-73.

12. Bercovitch L. Arch Dermatol 2011; 147(5): 588-9.

13. Arana A, Wentworth CE, Fernandez-Vidaurre C et al. Br J Dermatol 2010; 163: 1036-43.

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