Dr George Moncrieff discusses possible causes of atopic eczema and offers his personal approach to managing this distressing condition

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Read this article to learn more about:

  • how to diagnose atopic eczema
  • the use of emollients, topical steroids, and topical calcineurin inhibitors
  • when to refer for specialist review.

Key points

GP commissioning messages

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T here has been a relentless year-on-year increase in the prevalence of atopic diseases over the past 40 years, with atopic eczema now affecting over 20% of school-aged children in most developed countries.1,2

Food allergies were very uncommon 30 years ago when I entered general practice but now affect up to 8% of children.3 There is mounting evidence that damage to the infant skin barrier, as a result of our modern lifestyle, enables the penetration of allergenic proteins through the skin, triggering an abnormal allergic reaction in a genetically vulnerable individual. A compromised skin barrier is also one of the main drivers for atopic eczema and starts the 'atopic march', progressing to asthma and hay fever.4

The vast majority of patients with eczema are managed in primary care.5 It is important that we do not underestimate the adverse effect atopic eczema can have on patients' quality of life. Chronic skin irritation and scratching, along with repeated disturbed sleep not only interrupts education but also psychological development and can have a profound effect on the entire family.5,6

Guidance on atopic eczema

The management of atopic eczema in general practice should now be directed by a number of excellent sources:

  • NICE published Clinical Guideline 57 (CG57) on atopic eczema in children aged under 12 years in 20075 (NB a review is planned for May 2016)
  • Scottish Intercollegiate Guidelines Network (SIGN) Guideline 125 on the Management of atopic eczema in primary care was published in 2011;7 the SIGN guideline relates only to primary care, but includes atopic eczema in adult
  • the Primary Care Dermatology Society (PCDS) website includes a useful overview of atopic eczema alongside associated images for useful reference.8

Definition and diagnosis

Atopic eczema (or atopic dermatitis) is a chronic inflammatory skin condition characterised by itchy papules, typically in a flexural distribution. The lesions become excoriated and are often secondarily infected. Chronic rubbing results in lichenification. It is associated with a personal or family history of other atopic conditions.

In 1980, Hannifin and Rajka set out their diagnostic criteria.9 While the definition of atopic eczema recognises that this condition starts very early in life, it can also develop for the first time later in life. The diagnostic criteria were refined by the UK Working Party in 1994,10 by NICE in December 2007 (CG57),5 and remain current (see Box 1, below).

Box 1: Diagnostic criteria for atopic eczema5,9

 

Atopic eczema should be diagnosed when a child has an itchy skin condition plus three or more of the following:

  • visible flexural dermatitis involving the skin creases, such as the bends of the elbows or behind the knees (or visible dermatitis on the cheeks and/or extensor areas in children aged 18 months or under)
  • personal history of flexural dermatitis (or dermatitis on the cheeks and/or extensor areas in children aged 18 months or under)
  • personal history of dry skin in the last 12 months
  • personal history of asthma or allergic rhinitis (or history of atopic disease in a first-degree relative of children aged under 4 years)
  • onset of signs and symptoms under the age of 2 years (this criterion should not be used in children aged under 4 years).

Healthcare professionals should be aware that in Asian, black Caribbean and black African children, atopic eczema can affect the extensor surfaces rather than the flexures, and discoid (circular) or follicular (around hair follicles) patterns may be more common.

  • NICE. Atopic eczema in under 12s: diagnosis and management. Clinical Guideline 57.
  • NICE, 2007. Available at: nice.org.uk/guidance/cg57
  • Reproduced with permission

Pathophysiology

The skin barrier is critical to the management of atopic eczema. It prevents dehydration and retains moisture in the corneocytes as well as blocking the penetration of pathogens, potential allergens, and even ultraviolet light. Only recently have we begun to understand this remarkably sophisticated barrier.

Filaggrin (from fil ament aggr egating protein) is formed within granules in the stratum granulosa (SG), the layer of epidermal cells immediately below the stratum corneum (SC).8 This protein complexes with tonofilaments, collapsing the cells into stratified squamous epithelium. Filaggrin is then broken down into a large number of small, hydrophilic, acidic molecules (natural moisturising factors) that draw water into the cells and drop the pH. The pH at the junction between the SG and SC is around pH7, whereas the surface of the skin is acidic at around pH5. Filaggrin not only moderates the activity of the proteases that cleave the bonds (corneodesmosomes) that hold the corneocytes to one another, but is also an effective antiseptic.8

Another group of waxy chemicals, called ceramides, are also produced within granules in the SG. Ceramide droplets ooze out of the cells at the SG–SC junction and form an oily cement filling the spaces between the corneocytes.

Deeper in the epidermis, as part of the innate immune system, natural antimicrobial peptides (AMPs) are produced, which act as natural antibiotics (important examples are cathelicidin and defensin). Adaptive immune activities also play a crucial part in the skin's natural defence from infection. In genetically prone individuals, however, antigen exposure initiates abnormal T-cell activity and inflammatory pathways that result in atopic eczema.

For further discussion on the function of the epidermis, including a schematic diagram of the epidermis layers, please refer to my article published in the PCDS bulletin.11

Treatment

Emollients

Detergents clean the skin by removing grease, thereby removing dirt. That grease, though, acts as a water-impermeable membrane, and removing it compromises the barrier. Detergents also raise the surface pH to around pH8, which allows uncontrolled activity of surface proteases. This results in abnormal cleaving of corneocytes from one another and a breakdown in the barrier.11

Emollients are the cornerstone of managing eczema. Complete emollient therapy12 involves the use of semi-dispersing bath oils, emollients as soap substitutes, and leave-on emollients, ideally applied immediately after washing. In my experience, eczema will not settle unless detergents are replaced by emollients, and emollients still need to be used even when the skin is clear. Patients sometimes forget, for example, that shampoos are harsh detergents and allow these to rinse off over their entire skin.

Emollients are buffered to maintain the normal surface acidic environment. Any emollient can be used as a soap substitute apart from aqueous cream, which should never go anywhere near the skin, as it contains 1% sodium lauryl sulphate (a potent skin irritant).

Sometimes it is easier to apply the emollient before showering or entering the bath. Patients should be warned about the potential to render the shower tray or bath slippery, as well as clogging up the drain.

Choosing emollients

'best emollient' is the one that gets used and that depends enormously on patient preference. NICE CG57 states that emollients offered, 'may include a combination of products or one product for all purposes'.5 I find that allowing my patient to try a few options in my consulting room is a valuable opportunity, not only for my patient to choose the emollient they like, but also to ensure that they understand the importance of applying adequate quantities. For optimal effect, between 250 g and 500 g per week is needed in children (perhaps more in adults), so it is essential that adequate quantities are prescribed.5 This is also an opportunity to demonstrate correct application (i.e. not rubbing it on to the skin, but rather stroking it carefully and generously down in the direction of the hairs).5,7

All quality emollient creams are available in pump dispensers. The greasier ointments, which are naturally occlusive, come in tubs. Fingers should not be used to extract the emollient as this will rapidly result in bacterial contamination; instead, a clean spoon or spatula should be recommended.

For a more detailed discussion on emollient choices I once again refer you to an article I wrote for the PCDS bulletin.11

Topical corticosteroids

Both SIGN and the NICE guidelines recommend topical corticosteroids (TCS) as first-line therapy for atopic eczema.5,7 There is no doubt that these are highly effective. My preference is to start with a potent topical steroid, and then drop down to a milder potency as soon as control of the eczema has been gained. It should be noted that NICE CG57 recommends that:5

  • potent topical corticosteroids should not be used in children aged under 12 months without specialist dermatological supervision
  • very potent preparations should not be used in children without specialist dermatological advice.

In my opinion, TCS are best prescribed as ointments (these are naturally occlusive and having a very low water content, they do not contain any preservatives, which can sensitise). They only need to be applied once a day,13 so bedtime is ideal. It is important to treat all areas, though weaker steroids are appropriate for more delicate areas, such as flexures or the face. Consider treating for a few weeks after apparent clearance, perhaps just twice a week on 2 consecutive nights ('weekend therapy') for moderate to severe disease.5 One fingertip unit (FTU) weighs 0.5 g and is needed to cover an area of skin about the size of one hand.14

Review of TCS treatment

It is important to arrange review a few weeks after initiating a TCS, both to ensure the eczema has improved and that the treatment is being used appropriately. Patients are often needlessly alarmed by well-meaning friends, family, or even pharmacists regarding potential side-effects from TCS. This can result in their unfortunate under-use.

I also have some concerns however regarding their use! Although they undoubtedly calm the abnormal inflammation in eczema, they have a very broad-brush effect and can aggravate skin infections (especially fungal), by inhibiting both the adaptive immune and innate immune systems, such as the production of AMPs, which act as natural antibiotics (as discussed earlier).15

It is of course essential that emollients are continued throughout treatment with TCS as they increase the efficacy of TCS and have been shown to have a useful 'steroid sparing' effect.16,17

Topical calcineurin inhibitors

Two topical calcineurin inhibitors (TCIs) are available: tacrolimus ointment and pimecrolimus cream:

  • tacrolimus 0.03% ointment is licensed for moderate to severe atopic eczema in children from the age of 2 years;18 and tacrolimus 0.1% ointment is licensed for moderate to severe atopic eczema in those aged 16 years of age and over19
  • pimecrolimus 1% cream is licensed for mild to moderate eczema in patients aged 2 years and over.20

Tacrolimus has a similar potency to potent TCS and pimecrolimus has a similar effect to moderate potency TCS. Being an ointment, tacrolimus should not be used within 1 hour of application of an emollient. Pimecrolimus, being a cream, can be used synchronously, although a short interval would be ideal.20

These non-steroidal immunomodulating agents have earned an excellent reputation for effectiveness and safety. In my view (although current guidelines do not support this wholeheartedly) they are ideal primary care options that should be used early in the treatment cascade where treatment with TCS is either inadvisable or not possible.

In my practice, I usually reserve these agents for 'delicate areas', such as the eyelids or indeed anywhere on the face. Flexural areas are generally more sensitive to the potential sideeffects from TCS and again TCIs are relatively more appropriate.

I would suggest that TCIs should be used twice a day until the eczema is under control. The frequency can then drop down to twice a week for maintenance.

Adverse effects include some increased photosensitivity and stinging on application (especially with tacrolimus). In my experience, this can be helped by applying the ointment cold, straight from the fridge. Tacrolimus can induce facial flushing after consumption of an alcoholic beverage.18,19 There is a small risk of aggravating existing skin infection, so TCIs should not be started until any infection is under control. There has been some theoretical concern about the increased risk of malignancy, notably lymphoma,18,19 but no increased risk has been demonstrated and this should not limit use of TCIs.

Infection

Flares of eczema are often triggered by bacterial infection. I am eager, however, to avoid both topical and oral antibiotics wherever possible, so (and contrary to advice in the SIGN guideline7) I believe that the early use of topical antiseptics can avert the need for antibiotics.

There is a range of emollients that contain 0.1% chlorhexidine and benzalkonium that are safe and effective. In the presence of potentially more serious infection, I prefer the use of a hypoallergenic antimicrobial hair and body wash that contains octenidine, an antiseptic with no risk of sensitisation, and efficacy for viral, fungal, and bacterial infections (including aggressive infections such as Panton-Valentine Staphylococcus aureus).

Occasionally, I recommend a bath just once a week with a product that contains potent antiseptics (such as benzalkonium and triclosan).21 If the patient uses this type of product more frequently, though, it can cause quite marked irritation.

Antihistamines

Antihistamines have dropped out of my practice in recent years largely due to concerns regarding their anticholinergic effects and the potential for an adverse effect on cognitive function. They are, however, reasonable for short-term use, to help to break the itch-scratch-itch cycle, enable rest, and restore skin to normal. NICE and SIGN recommend short-term use of sedating antihistamine for children during an acute flare if sleep disturbance is a problem.5,7

When to refer

Both the NICE and SIGN guidelines highlight the importance of immediate referral to secondary care if eczema herpeticum is suspected.5,7 The PCDS has useful information on its website on eczema herpeticum.

Urgent (within 2 weeks) referral for specialist dermatological advice is recommended for children if:5

  • their atopic eczema is severe and has not responded after 1 week to optimum topical therapy
  • treatment of their bacterially infected atopic eczema has failed.

Children should be referred for specialist dermatological advice if there is:5,7

  • diagnostic uncertainty
  • poor control (based on a subjective assessment)
  • atopic eczema on the face that has not responded to appropriate treatment
  • psychological upset or sleep problems
  • suspicion of contact dermatitis
  • an educational need related to treatment application
  • severe and recurrent infection.

Conclusion

Atopic eczema is a common condition that can have a devastating effect on the patient and their family. Often simple lifestyle changes, such as effective use of emollients and avoiding exposure to detergents, is all it takes to settle this condition, but when it is more severe and these measures alone are inadequate, we now have some safe and effective, products that can help in the vast majority of cases. Our role in primary care is to manage this cohort of patients well, at the same time as remaining vigiliant for those patients who need secondary care resources either urgently or routinely.

 

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Key points

  • Atopic eczema is becoming increasingly prevalent year on year
  • Evidence suggests that atopic eczema and the 'atopic march' arises from changes to the skin barrier in genetically vulnerable individuals
  • Atopic eczema can disrupt sleep, education, and psychological development and can have a profound effect on a family’s quality of life
  • Emollients are essential in the treatment of atopic eczema:
    • adequate quantities should be prescribed and patient preferences respected
  • SIGN and NICE guidelines recommend topical steroids as first-line therapy:
    • emollients should be continued throughout steroid therapy
  • Non-steroidal immunomodulating agents (tacrolimus and pimecrolimus) are licensed from 2 years of age
  • Sedating antihistamines may be used short-term where there is debilitating sleep disturbance
  • If eczema herpeticum is suspected, refer immediately to secondary care.

SIGN=Scottish Intercollegiate Guidelines Network

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GP commissioning messages

written by Dr David Jenner, GP Cullompton Devon

  • Atopic eczema is a common condition that is often sub-optimally managed in primary care
  • Local formularies should:
    • define a series of cost-effective options for emollients and topical steroids and give guidance on appropriate quantities to be prescribed for adults and children
    • describe the indications for use and precautions for prescribing TCIs, which can be very useful (although more expensive), particularly for facial eczema
  • CCGs should consider commissioning interface GPwSI or specialist nurse services to support GPs in the management of these conditions, so reducing the need for specialist hospital services
  • Pharmacists, both within practices and in community services, could have a key role in a advising patients and their carers on the optimal use of emollients and other topical agents.

TCIs=topical calcineurin inhibitors; GPwSI=GP with a special interest

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References

  1. Herd R, Tidman M, Prescott R, Hunter J. Prevalence of atopic eczema in the community: the Lothian atopic dermatitis study. Br J Dermatol 1996; 135: 18–19.
  2. Flohr C, Mann J. New insights into the epidemiology of atopic dermatitis. Allergy 2014; 69 (1): 3-16
  3. Gupta R et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics 2011; 128 (1): e9–e17.
  4. Lack G. Epidemiologic risk for food allergy. J Allergy Clin Immunol 2008; 121 (6): 1331–1336.
  5. NICE. Atopic eczema in under 12s: diagnosis and management. Clinical Guideline 57. NICE, 2007. Available at: nice.org.uk/guidance/cg57
  6. Barnetson R, Rogers M. Childhood atopic eczema. BMJ 2002; 324: 1376–1379
  7. Scottish Intercollegiate Guidelines Network. Management of atopic eczema in primary care. SIGN 125. SIGN, 2011. Available at: sign.ac.uk/pdf/sign125.pdf
  8. Primary Care Dermatology Society website. Eczema: atopic eczema. Available at: www.pcds.org.uk/clinical-guidance/atopiceczema#images (accessed 24 February 2016).
  9. Hanifin J, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermatovener 1980; 92 (Suppl): 44–47.
  10. Williams H, Burney P, Pembroke A, Hay R and Atopic Dermatitis Diagnostic Criteria Working Party (1994). The UK Working Party’s diagnostic criteria for atopic dermatitis. III. Independent hospital validation. Br J Dermatol 1994; 131 (3): 406–416.
  11. Moncrieff G. Complete emollient therapy—a personal view. Primary Care Dermatology Society bulletin. Spring 2013, pp.9–14. Available at: www.pcds.org.uk/ee/images/uploads/bulletins/Spring_bulletin_2013-web.pdf
  12. Cork M, Danby S. Skin barrier breakdown: a renaissance in emollient therapy. Br J Nurs 2009; 18 (14): 872–877.
  13. Green C, Colquitt J, Kirby J et al. Clinical and cost-effectiveness of once-daily versus more frequent use of same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation. Health Technology Assessment; 2004; 8 (47).
  14. Long C, Finlay A. The finger-tip unit—a new practical measure. Clin Exp Dermatol 1991; 16 (6): 444–447.
  15. Gallo R, Hooper L. Epithelial antimicrobial defence of the skin and intestine. Nature Reviews Immunology 2012. 12: 503–516.
  16. Berth-Jones J, Damstra R, Golsch S et al. 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 (7403): 1367–1370.
  17. Szczepanowska J, Reich A, Szepietowski J. Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomised comparative study. Pediatr Allergy Immunol 2008; 19 (7): 614–618.
  18. Protopic 0.03% ointment—summary of product characteristics. December 2015. Available at: www.medicines.org.uk/emc/medicine/8884 (accessed 24 February 2016).
  19. Protopic 0.1% ointment—summary of product characteristics. December 2015. Available at: www.medicines.org.uk/emc/medicine/8816 (accessed 24 February 2016).
  20. Elidel 10 mg/g cream—summary of product characteristics. August 2013. Available at: www.medicines.org.uk/emc/medicine/25482 (accessed 24 February 2016).
  21. Oilatum Plus—summary of product characteristics. December 2015. Available at: www.medicines.org.uk/emc/medicine/2118 (accessed 24 February 2016). G