Atopic eczema: clinical review

The causes of atopic eczema and advice on managing the condition, including diagnostic criteria, clinical presentation, the role of antihistamines and patient education.

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base


Section 1: Epidemiology and aetiology

Atopic eczema (AE) is a chronic, relapsing-remitting inflammatory 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 1-2% in adults.1,2 Some 50% of childhood AE occurs before the age of one year and up to 90% occurs before the age of five years.3

Physiology of the skin barrier
The outermost skin barrier, the stratum corneum, is made up of corneocytes surrounded by a lipid lamellar matrix. The corneocytes contain natural moisturising factor (NMF) with humectants, such as urea, which retain water and reduce transepidermal water loss (TEWL) while maintaining the skin pH at 5.5.1 Corneocytes are held together by corneodesmosomes, which are broken down by protease enzymes during desquamation.

NMF is produced by breakdown of filaggrin, a stratum corneum protein. Changes in water content of the stratum corneum trigger filaggrin degradation.4

Genetic, immunologic and environmental factors are responsible for breakdown in skin barrier function, the primary event in the development of AE.

Genetic and immunologic factors
Mutations in the filaggrin gene predispose to AE.1 In the UK, up to 50% of patients with AE are heterozygous for one of the mutations.5 

Deficient levels of filaggrin result in reduced NMF and decreased ability of corneocytes to retain water as well as increased skin pH which triggers increased protease activity. Furthermore, mutations in protease enzyme genes induce excessive protease activity leading to a thin stratum corneum susceptible to penetration of irritants.6

Deficiency in genetic expression of antimicrobial peptides (B-defensins and cathelicidin) in AE accounts for increased susceptibility to cutaneous infections especially Staphylococcus aureus.2 Some 90% of patients have skin colonised by Staph aureus whose toxins act as superantigens stimulating inflammatory response and damage to the skin barrier.7 A defective T-cell mediated immunity predisposes to severe herpes simplex infection of the skin; eczema herpeticum.8

Familial predisposition to increased serum IgE antibodies and sensitisation to various allergens is seen in people with an ‘atopic tendency’ and an increased susceptibility to developing atopic eczema, asthma and allergic rhinitis.

Environmental factors
Surfactants, such as soap, shower gels 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 that is susceptible to allergen and microbial penetration. The release of inflammatory cytokines triggers itching and a vicious itch-scratch-itch cycle causes further skin barrier damage (see figure, aetiology of atopic eczema, below).

Important! Soap, shower gels and detergents emulsify skin lipids, reduce corneocyte water retention and increase transepidermal water loss.


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).

Clinical 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 type of AE with predominantly itchy excoriated nodular lesions (prurigo nodularis) which can be difficult to manage. Assessment of severity should include extent of skin involvement, degree of inflammation and the impact on quality of life.

Secondary bacterial and viral infections are common and may modify the clinical picture. Staphylococcal impetiginisation of eczematous lesions leads to yellow impetigo-like crusting and weeping. Bacterial cultures are of little value because of high prevalence of colonisation 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 and clinically this presents as sudden worsening eczema with punched out vesicles at the same stage of development.

Differential diagnoses should include other types of eczema, such as contact and irritant eczema, which often coexist especially in adults. Psoriasis and dermatophyte infections are important differentials to consider, particularly where the disease affects the hands and feet. Scabies should also be considered.

Important! Assessment of severity should include extent of skin involvement, degree of inflammation and the impact on quality of life.


Section 3: Managing the condition

The primary treatment aims in AE are to improve skin barrier function, suppress inflammation and control infection.

Maintenance of skin barrier
Emollient therapy tailored to the needs of the patient and used at all times decreases disease severity and the need for pharmacological treatment. 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.9 

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. Leaving intervals of 30 minutes after applying emollient before topical anti-inflammatories reduces dilution and possible interference with stability and absorption of medication.9

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

Important! Patients should be advised to bathe once a day for no longer than 20 minutes to reduce waterlogging, which weakens the lipid layer, leading to dryness.

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

During flares, a step-up approach is used in which a moderate to high potency preparation is used once or twice daily for up to a week and discontinued or stepped-down to a low potency preparation. Systemic steroids should be avoided at all times.

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.10

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

Both TCS and TCIs can be used proactively twice a week as maintenance therapy after remission in patients with frequent severe flares.

Antimicrobial therapy
The 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 or when there is clinical sign of bacterial infection.7

A combined topical steroid and antibiotic regimen for up to two weeks may be indicated. Antiseptics (triclosan and chlorhexidine), with a low sensitising potential may be useful to reduce Staph aureus colonisation.3

Role of antihistamines and patient education
Sedative antihistamines may be useful in the short term, during relapses associated with severe pruritus with sleep disturbance or urticaria, in patients over the age of six months.

Patient education on prevention of aggravating factors (including appropriate clothing and cool temperature at nighttime), early identification of flares and correct topical treatment application is important.

A good understanding of indications for referral to secondary care is essential. These include diagnostic uncertainty, severe eczema responding poorly to treatment, eczema herpeticum, excessive use of TCS or TCIs, suspected contact dermatitis and growth faltering in children.


Section 4: Prognosis

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

Disease persistence
Patients with early-onset AE and filaggrin mutations tend to have persistent disease into adulthood.7

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.3,11,12AE is a major risk factor for developing asthma. Around 70% of patients with severe AE develop asthma, compared with 8% of the general population.13

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.

AE itself is associated with anterior and posterior subcapsular cataracts with prevalence ranging from 1% to 25%.14 The cause of the cataracts is unknown, however, it has been suggested that habitual rubbing of the face may play a part.15 Patients applying topical corticosteroids to the eyelids for over four weeks should ideally undergo intra-ocular pressure measurements, and if possible, be prescribed TCIs instead.14

Adults with AE especially those with sleep disturbances have higher rates of CVD risk factors and depression with significant negative impact on quality of life.16

Important! Around 70% of patients with severe AE develop asthma, compared with 8% of the general population.


Section 5: Case study

A four-year-old boy is referred with an eight-month history of poorly controlled eczema. He has had recurrent episodes of infection requiring repeated courses of antibiotics. He has a history of AE from the age of six months. His sleep is disturbed and he often wakes with blood on his pyjamas.

His mother is concerned about side effects of topical steroids so she has 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 consists of an emollient as a soap substitute and an ointment used twice a day. His mother notes that the ointment made his skin itchier so he sometimes refused to use it.

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

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

A diagnosis of moderate to severe AE with secondary infection is made. Bacterial swabs are 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 is commenced. This consists 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 antibiotic for seven days; a moderately potent steroid cream and a sedating antihistamine at night for 14 days.

Time is 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 is demonstrated.

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


Section 6: Evidence base

Clinical trials

The gene-environment interaction and its effect on epidermal barrier and development of atopic eczema 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.

  • Dalgard FJ, Gieler U, Tomas-Aragones L, et al. The Psychological burden of skin diseases: cross-sectional multicenter study among dermatological outpatients in 13 European countries. J Invest. Derm. 2015; 135:984-991.

This study highlights the significant impact of skin diseases such as atopic eczema on quality of life and in particularly the impact on mental health

Guidelines

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

  • Primary Care Dermatology Society. Eczema - atopic eczema. July 2016 This is a comprehensive guide to the clinical presentation, and management of atopic eczema.

Key text

  • Evidence based dermatology (third edition). Editor H. Williams. BMJ books, Wiley Blackwell Publishing, 2014.

The chapter on atopic dermatitis is well written and concise. It covers the application of evidence in the management of atopic eczema.

Online

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

This is a good resource for clinical guidelines.

  • Dr Rufaro Gamanya, General Practitioner, Parc Canol Group Practice, South Wales, UK

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References

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  2. Bieber T. Ann Dermatol 2010; 22(2): 125-37.
  3. Silverberg JL, Garg NK, Paller AS et al. J Invest Derm 2015; 135:56-66.
  4. Sandilands A, Sutherland C, Irvine AD et al. J Cell Sci 2009; 122(9): 1285-94.
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  6. Novak N, Peng W. Arch Immunol Ther Exp 2016: May 4; (Epub ahead of print)
  7. Sidbury R, Davis DM, Cohen DE et al. J. Am Acad Dermatol 2014; 71:327-349.
  8. Takahashi R, Sato Y, Kurata M et al. J Immunol 2014;192:969-978.
  9. Peters J. Br J Comm Nurs 2001; 6(12): 645-51.
  10. Baldo A, Cafiero M, Caterino P et al. Clin Cosmet Investig Dermatol 2009; 2: 1-7.
  11. Rance F, Boguniewicz M, Lau S et al. Pediatr Allergy Immunol 2008; 19 (suppl 19): 17-25.
  12. Sandstrom MH, Faergemann J. Br J Dermatol 2004; 150: 103-10.
  13. Zheng T, Jinho Y, Oh MH et al. Allergy Asthma Immunol Res 2011; 3(2): 67-73.
  14. Bercovitch L. Arch Dermatol 2011; 147(5): 588-9.
  15. Arana A, Wentworth CE, Fernandez-Vidaurre C et al. Br J Dermatol 2010; 163: 1036-43.
  16. Silverberg JL, Greenland P. J Allergy Clin Immunol 2015; 135:721-728.

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