Eczema (atopic)

Fiona Bath-Hextall; Hywel Williams

. 2006 Jul 1;2006:1716.

Eczema (atopic)

Fiona Bath-Hextall ^1,^#, Hywel Williams ^2,^#

PMCID: PMC2907628

Abstract

Introduction

Atopic eczema affects 15-20% of schoolchildren worldwide and 2-10% of adults. Only about 60% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of self-care treatments, topical medical treatments, and dietary interventions in adults and children with established atopic eczema? What are the effects of breast feeding as a primary preventive intervention in predisposed infants? What are the effects of reducing allergens as a primary preventive intervention in predisposed infants? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: breast feeding, controlling house dust mites, corticosteroids, dietary exclusion of eggs or cows' milk, elemental diets, emollients, essential fatty oils, few-foods diet, multivitamins, pimecrolimus, probiotics, pyridoxine, reducing maternal dietary allergens, tacrolimus, vitamin E, and zinc supplements.

Key Points

Atopic eczema affects 15-20% of schoolchildren worldwide and 2-10% of adults. Only about 60% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens.

Remission occurs in two thirds of children by the age of 15 years, but relapses may occur later.

There is a consensus that emollients are effective for treating the symptoms of atopic eczema, although little high quality research has been done to confirm this.

Corticosteroids improve clearance of lesions and decrease relapse rates compared with placebo, although we don't know which is the most effective corticosteroid or dosing regimen.

Topical corticosteroids seem to have few adverse effects, but may cause burning, skin thinning and telangiectasia, especially in children.

Pimecrolimus and tacrolimus improve clearance of lesions compared with placebo and may have a role in people with a high risk of corticosteroid adverse effects.

CAUTION: An association has been suggested between pimecrolimus and tacrolimus and skin cancer. They should be used only where other treatments have failed.

We don't know whether vitamin E, pyridoxine, zinc supplementation, exclusion or elemental diets or probiotics reduce symptoms in atopic eczema, as there are insufficient good quality studies.

Essential fatty acids such as evening primrose oil, blackcurrant seed oil or fish oil do not seem to reduce symptoms in atopic eczema.

We don't know whether prolonged breast feeding, reducing maternal dietary allergens, or control of house dust mites, can prevent the development of atopic eczema in children.

Early introduction of probiotics in the last trimester of pregnancy and during breastfeeding may reduce the risk of atopic eczema in the baby.

About this condition

Definition

Atopic eczema (also known as atopic dermatitis) is a chronic, relapsing, and itchy inflammatory skin condition. In the acute stage, eczematous lesions are characterised by poorly defined erythema with surface change (oedema, vesicles, and weeping). In the chronic stage, lesions are marked by skin thickening (lichenification). Although lesions can occur anywhere on the body, babies often have eczematous lesions on their cheeks and outer limbs before developing the more typical flexural involvement behind the knees and in the folds of the elbow and neck later in childhood. Atopy, the tendency to produce specific immunoglobulin E responses to allergens, is associated with "atopic" eczema, but up to 60% of individuals with the disease phenotype may not be atopic. This can cause confusion, for example around diagnosis, treatment, lifestyle recommendations, and genetic markers. The correct use of the term atopic eczema should therefore ideally only refer to those with a clinical picture of eczema who are also immunoglobulin E antibody high-responders. Diagnosis: There is no definitive "gold standard" for the diagnosis of atopic eczema, which is based on clinical features combined with a disease history. However, a UK working party developed a minimum list of reliable diagnostic criteria for atopic eczema using the Hanifin and Rajka list of clinical features as building blocks (see table 1 ). In an independent validation study of children attending hospital dermatology outpatients, the criteria were shown to have a sensitivity of 85% and a specificity of 96% when compared with a dermatologist′s diagnosis. There are several severity scoring systems, used mainly in clinical trials, including the SCORing Atopic Dermatitis (SCORAD) and the six area, six sign atopic dermatitis severity score (SASSAD) indexes (see table 2 ). Quantitative scales used for measuring atopic eczema severity in clinical trials are too complex and difficult to interpret in clinical practice. The division of atopic eczema into mild, moderate, and severe mainly depends on the intensity of itching symptoms (e.g. resulting in sleep loss), the extent of involvement, and course of disease. Population: For the purposes of this review, we included all adults and children defined as having established atopic eczema. Where either adults or children are considered separately, this is highlighted in the text. We also included studies assessing primary prevention in those at risk of developing atopic eczema for specific interventions: prolonged breast feeding, maternal dietary restriction, house dust mite restriction, and early introduction of probiotics.

Table 1.

UK Working Party Diagnostic Criteria for Atopic Eczema (see text).

An individual must have an itchy skin condition (or parental report of scratching or rubbing) in the last 12 months, plus three or more of the following:
(i) a history of involvement of the skin creases (fronts of elbows, behind knees, fronts of ankles, around neck, or around eyes)
(ii) a personal history of asthma or hay fever (or history of atopic disease in a first degree relative if a child is aged under 4 years)
(iii) a history of a generally dry skin in the last year
(iv) onset under the age of 2 years (not used if a child is aged under 4 years) or visible flexural dermatitis (including dermatitis affecting cheeks or forehead and outer aspects of limbs in children under 4 years).

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Table 2.

Research criteria for assessing severity in atopic eczema (see text).

The SCORing Atopic Dermatitis (SCORAD) index

Total score is calculated from:

Extent of affected areas: calculated as a percentage of total body area (from chart)
Intensity of a typical lesion (each scored 0 = none, 1 = mild, 2 = moderate, 3 = severe):
Erythema
Oedema/papulation
Oozing/crust
Excoriation
Lichenification
Dryness of unaffected areas

Subjective symptoms:
Pruritus (0–10 visual analogue scale)
Sleep loss (0–10 visual analogue scale)

SCORAD = extent score/5 + 7 × intensity score/2 + subjective symptoms score

Half of all atopic patients score between 28 and 54 points. For a simple guide to using SCORAD in practice, see http://adserver.sante.univ-nantes.fr/Scorad_Course/How.html (last accessed 23 February 2006).

Six area, six sign a topic dermatitis severity index (SASSAD)
Six sites of the body are assessed for each of six features, each one scoring 0–3 for increasing severity:

Erythema
Exudation
Excoriation
Dryness
Cracking
Lichenification

This scale correlates with global assessments of disease severity, but not with quality of life scores.

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Incidence/ Prevalence

Atopic eczema affects 15-20% of school age children at some stage, and 2-10% of adults in the UK. Prevalence data for the symptoms of atopic eczema were collected in the global International Study of Asthma and Allergies in Childhood (ISAAC). The results of the study suggest that atopic eczema is a worldwide problem affecting 5-20% of children. One UK based population study showed that 2% of children under the age of 5 years have severe disease and 84% have mild disease. Around 2% of adults have atopic eczema, and many of these have a more chronic and severe form.

Aetiology/ Risk factors

The causes of eczema are not well understood and are probably due to a combination of genetic and environmental factors. In recent years, research has pointed to the possible role of environmental agents such as house dust mites, pollution, and prenatal or early exposure to infections. The world allergy association's revised nomenclature for allergy also states that what is commonly called atopic eczema is not one specific disease but encompasses a spectrum of allergic mechanisms.

Prognosis

Remission occurs by the age of 15 years in 60-70% of cases, although some relapse may occur later. Although no treatments are currently known to alter the natural history of atopic eczema, several interventions can help to control symptoms. Development and puberty may be delayed in the more severely affected child.

Aims of intervention

To prevent atopic eczema in predisposed infants and children; to minimise the impact of established atopic eczema on quality of life in children and adults.

Outcomes

Prevention of development of atopic eczema; severity of symptoms (itching, sleep disturbance) and signs (erythema, oozing/crusting, lichenification, cracking, oedema, excoriation, dryness); reduction in surface area affected (sometimes described in this chapter as clearance); prevention of relapse (sometimes described in this chapter as maintenance); quality of life; area of skin involvement; adverse effects of treatments. Trials use a large number of atopic eczema scoring systems, including composite quantitative scales such as SCORing Atopic Dermatitis (SCORAD), six area, six sign atopic dermatitis severity scale (SASSAD), Rajka and Langeland scoring system, and the dermatology life quality index. These vary in the degree that they have been validated, and many more completely non-validated scales are in use.

Methods

Clinical Evidence search and appraisal February 2005. The following databases were used to identify studies for this chapter: Medline 1966 to September 2006, Embase 1980 to September 2006, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2006, Issue 3. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved were assessed independently by two information specialists using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this chapter were: published systematic reviews and RCTs in any language, open or blinded, and containing more than 20 individuals per arm of whom more than 80% were followed up. There was no minimum length of follow up required to include studies. We also did a search for observational studies on harms of tacrolimus. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the chapter as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for Atopic eczema

Important outcomes	Disease severity, symptom relief, relapse, quality of life, adverse effects
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of self-care treatments in adults and children with established atopic eczema?
5 (504)	Symptom severity	Emollients v placebo,	4	–2	–1	–2	0	Very low	Quality points deducted for poor methodology and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for assessing different outcomes and relevance of comparators
3 (356)	Symptom severity	Emollients v other emollients	4	–2	–1	–1	0	Very low	Quality point deducted for poor methodology and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for relevance of comparators used
1 (72)	Symptom severity	Emollients v mild corticosteroids	4	–3	0	–1	0	Very low	Quality points deducted for sparse data, incomplete reporting of results, and short follow-up. Directness point deducted for few comparators
2 (643)	Relapse rate	Emollients v potent corticosteroids	4	–2	+1	–1	0	Low	Quality point deducted for uncertainty of assessment score and incomplete reporting. Consistency point added for dose response. Directness point deducted for relevance of comparator used
1 (91)	Symptom severity	Emollients v potent corticosteroids plus emollients	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (94)	Symptom severity	Corticosteroids v placebo (peanut oil vehicle)	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for relevance of comparator used in intervention
2 (439) t	Symptom severity	Corticosteroids v each other	4	–1	–1	-0	0	Low	Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results
2 (624)	Relapse rate	Corticosteroids v each other (frequency of application)	4	–1	–1	–2	0	Very low	Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for relevance of comparator used
12 (2884)	Symptom severity	Pimecrolimus v placebo (vehicle cream)	4	0	–1	0	0	Moderate	Consistency point deducted for different results at different endpoints
1 (658)	Symptom severity	Pimecrolimus v mild corticosteroid	4	–1	–1	–2	0	Very low	Quality point deducted for poor follow-up. Consistency point deducted for conflicting results. Directness points deducted for combining interventions and inclusion of patients with severe eczema
2 (745)	Symptom severity	Pimecrolimus v potent corticosteroid	4	–1	–1	–1	0	Very low	Quality point deducted for poor follow-up. Consistency point deducted for conflicting results. Directness point deducted for combined regimen
1 (141)	Symptom severity	Pimecrolimus v tacrolimus	4	–1	0	0	0	Moderate	Quality point deducted for sparse data
1 (49)	Symptom severity	Pimecrolimus v each other (frequency of application)	4	–2	0	-1	0	Very low	Quality point deducted for sparse data and poor follow-up. Directness point deducted for inclusion of patients with severe eczema
4 (1286)	Symptom severity	Pimecrolimus v placebo (vehicle cream)	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of patients with severe eczema
6 (1745)	Adverse effects	Pimecrolimus v corticosteroids	4	0	0	0	0	High
4 (792)	Symptom severity	Tacrolimus v vehicle cream	4	–1	0	0	0	Moderate	Quality point point deducted for incomplete reporting
3 (985)	Quality of life	Tacrolimus v placebo (vehicle)	4	0	0	0	0	High
4 (2294)	Symptom severity	Tacrolimus v mild corticosteroid	4	0	0	–1	+1	High	Directness point deducted for combined regimen. Effect size point added for relative risk greater than 2
3 (1719)	Symptom severity	Tacrolimus v potent corticosteroids	4	0	–1	–1	0	Low	Consistency point deducted for conflicting results. Directness point deducted for different regimens used
6 (1351)	Symptom severity	Lower tacrolimus dose v higher dose	4	0	–1	–1	0	Low	Consistency point deducted for conflicting results. Directness point deducted for assessing different outcomes
14 RCTs (4209)	Adverse effects	Tacrolimus v placebo (vehicle cream)	4	0	0	0	0	High
What are the effects of dietary interventions in adults with established atopic eczema?
2 (156)	Symptom severity	Vitamin E v placebo, v selenium, v selenium plus vitamin E	4	–2	–1	–1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for uncertain significance of outcome
1 (59)	Symptom severity	Vitamins B and E alone compared with Vitamin E plus Vitamin B2	4	–3	0	0	0	Very low	Quality points deducted for sparse data, lack of placebo, incomplete reporting of results, and poor follow-up
What are the effects of dietary interventions in children with established atopic eczema?
1 (73)	Symptom severity	Cows' milk formula v amino acid-based formula	4	–1	0	–3	0	Very low	Quality points deducted for sparse data. Directness point deducted for lack of comparison between groups, uncertainty about significance of outcomes, and narrow inclusion criteria
1 (58)	Symptom severity	Probiotics v placebo	4	–2	0	–2	0	Very low	Quality points deducted for sparse data and methodological flaws. Directness point deducted for lack of comparison between groups and uncertainty of significance of outcome
1 (85)	Symptom severity	Few-foods diets v usual diet	4	–3	0	0	0	Very low	Quality points deducted for sparse data, no intention-to-treat analysis, poor follow-up, and incomplete reporting of results
1 (50)	Symptom severity	Zinc supplements v placebo	4	–1	0	0	0	Moderate	Quality points deducted for sparse data
1 (48)	Symptom severity	Pyridoxine v placebo	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
21 (1508)	Symptom severity	Essential fatty acids v placebo	4	–2	0	0	0	Low	Quality point deducted for incomplete results and inclusion of CCTs
What are the effects of breast feeding as a primary preventive intervention in predisposed infants?
14 studies (4158)	Development of atopic eczema	Breast feeding v bottle feeding	2	–1	0	0	0	Very low	Quality point deducted for methodological flaws
What are the effects of reducing allergens as a primary preventive intervention in predisposed infants?
9 (1227)	Development of atopic eczema	Maternal antigen avoidance diet v no avoidance	4	–3	–1	0	0	Very low	Quality points deducted for uncertainty of randomisation, methodological flaws, and no intention-to-treat analysis. Consistency point deducted for conflicting results
1 (696)	Development of atopic eczema	Allergen avoidance (house mite reduction) v allergen avoidance advice v basic information about allergies	4	0	0	–1	0	Moderate	Directness point deducted for relevance of comparators
1 (159)	Development of atopic eczema	Early introduction of probiotics v placebo	4	–1	0	–1	0	Low	Quality point deducted for sparse data. Directness point deducted for narrow inclusion criteria

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Type of evidence: 4 = RCT; 2 = Observational; Consistency: similarity of results across studies.Directness: generalisability of population or outcomes.Effect size: based on relative risk or odds ratio.

Glossary

Allergens: Allergens are foreign chemicals to which the body has become sensitive, and can cause an allergy in hypersensitive persons and thus an allergic reaction.
Atopic: Inherited tendency to develop allergic reactions associated with an immunoglobulin E response.
Corticosteroids: synthetic glucocorticoids (similar to hormones) are used to treat atopic eczema, among other diseases, to suppress inflammation, allergy, and immune responses.
Dry skin area and severity index: A newly proposed system for dry skin and ichthyosis, where the score is calculated as the product of the sum of severity scores and area affected in four body regions.
Emollients: skin moisturisers used in the management of many dry skin problems, including atopic eczema.
Few foods diet: A diet that is based on just a few foods, such as lamb, rice, and carrots, which is then progressively widened.
High-quality evidence: Further research is very unlikely to change our confidence in the estimate of effect.
Intertriginous areas: Areas of the body where skin is in contact with other areas of the skin such as armpits, groin, and under breasts.
Low-quality evidence: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Moderate-quality evidence: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Probiotics: Viable bacteria that colonise the intestine and alter the microflora and their metabolic activities, with a presumed beneficial effect for the host. Many probiotics are lactic acid bacteria – for example, Lactobacillus or bifidobacterium. Not all probiotics have the same properties or effectiveness.
SASSAD index: The six area, six sign atopic dermatitis severity index is a scoring system to measure the severity of atopic eczema. Six sites of the body are assessed for each of six features, each one scoring 0–3 for increasing severity.
SCORAD index: The SCORing Atopic Dermatitis (SCORAD) index is a scoring system designed by the European Task Force on Atopic Dermatitis to measure the severity of atopic eczema. It has five clinical signs: erythema, vesiculation, excoriation, crusting, and oedema. Each of these signs has four scores: 0 = absent; 1 = mild, 2 = moderate, and 3 = severe.
Very low-quality evidence: Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Fiona Bath-Hextall, The University of Nottingham, Faculty of Medicine and Health Sciences, Nottingham, UK.

Hywel Williams, The University of Nottingham University Hospiital, Queen's Medical Centre, Nottingham, UK.

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BMJ Clin Evid. 2006 Jul 1;2006:1716.

Emollients (alone or plus topical steroids)

Summary

SYMPTOM SEVERITY Compared with placebo: We don't know whether emollients are more effective than placebo at reducing skin dryness in atopic eczema ( very low-quality evidence ). Compared with other emollients: We don't know which emollient is more effective in reducing skin dryness in atopic eczema (very low-quality evidence). Compared with mild corticosteroids: Emollients (kamillosan cream) may be more effective compared with mild corticosteroids (0.5% hydrocortisone cream) in relieving symptoms of atopic eczema (very low-quality evidence). Compared with corticosteroids plus emollients: Emollients alone may be less effective in improving symptoms of atopic eczema compared with corticosteroids plus emollients ( low-quality evidence ). RELAPSE RATES Compared with potent corticosteroids: Emollients may be less effective in reducing relapse rates of atopic eczema at 16 weeks compared with a potent corticosteroid, fluticasone propionate (0.05%), used intermittently twice a week (low-quality evidence). Compared with corticosteroids plus emollients: Emollients may be less effective in reducing relapse rates compared with corticosteroids plus emollients ( low-quality evidence ). ADVERSE EFFECTS Emollients have been associated with transient burning. NOTE We found no clinically important results about the effects of emollients plus mild corticosteroids in atopic eczema.

Benefits

Emollient versus placebo:

We found one systematic review (search date 1999, 2 RCTs), which identified two RCTs of poor quality and three subsequent RCTs. The RCTs provided insufficient evidence to assess the effect of emollient versus placebo on skin dryness (see table 3 ).

Table 3.

RCTs comparing emollients versus placebo (see text)

Study	Methods	Participants	Outcomes	Results	Significance
	First RCT identified by systematic review	80 adults and children with atopic eczema	Skin redness, hydration, and induration	10% urea cream improved skin redness, hydration and induration compared with a vehicle	Not assessed
	Second RCT identified by systematic review	46 children with atopic eczema	Skin hydration, lichenification, and erythema	6% ammonium lactate significantly reduced lichenification at day 15 and erythema at day 30 compared with the cream base alone	Reported as significant
	First subsequent RCT	109 adults, mean age 34 years, with atopic eczema	Skin dryness severity score at 30 days	No significant difference between glycerine and placebo	Results presented graphically; p = 0.419
	Second subsequent RCT	197 adults, mean age 35 years, with atopic eczema	Skin dryness severity score at 30 days	No significant difference between glycerine cream and placebo at 1 month	Percentage of group improved: 85% with glycerin v 63% with placebo; p = 0.565
	Third subsequent RCT	72 adults, mean age 45.5 with moderate atopic eczema	Skin pruritus, erythema, and desquamation	Kamillosan cream marginally improved skin pruritus, erythema, and desquamation compared with placebo and 0.5% hydrocortisone	Significance assessment not performed

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Emollients versus each other:

We found one systematic review and two subsequent RCTs. The systematic review identified one RCT of poor quality (50 people, aged 18–55 years). It found no significant difference between a new 5% urea cream compared with an established licensed cream containing 4% urea. The first subsequent RCT (109 people with atopic eczema) found that 4% urea plus 4% sodium chloride cream reduced skin dryness severity score to a significantly greater extent than glycerin cream at 30 days (dry skin area and severity index; results presented graphically; p = 0.024). The second, similar RCT (197 adults, mean age 35 years) found no significant difference between 20% glycerin and 4% urea plus 4% sodium chloride cream in disease severity (using Duke activity status index scores) or skin dryness at 30 days (results presented graphically; disease severity; p = 0.787; skin dryness, p = 0.77).

Emollients versus mild corticosteroid:

See benefits of mild corticosteroids in topical medical treatments.

Emollients versus potent corticosteroid:

See benefits of potent corticosteroids in topical medical treatments.

Emollients plus mild corticosteroid:

We found no RCTs of sufficient quality.

Emollients plus potent corticosteroid:

See benefits of potent corticosteroid in topical medical treatments.

Harms

Emollients versus placebo:

One RCT found a similar proportion of people with transient burning with urea cream compared with vehicle cream (absolute figures not reported; significance assessment not performed). The other RCTs did not report on harms.

Emollients versus each other:

The RCTs gave no information on adverse effects.

Emollients versus mild corticosteroids:

The RCT gave no information on adverse effects.

Emollients versus potent corticosteroids:

The RCTs gave no information on adverse effects with emollients.

Emollients plus mild corticosteroids:

One RCT identified by the review found that one person experienced a burning sensation when the oil in water emollient was applied. Another RCT identified by the review found no significant difference between 0.05% desonide lotion alone versus 0.05% desonide lotion plus moisturising cream three times daily in the proportion of people who reported sting or burning on the treated side at 1 week (14% with 0.05% desonide lotion v 12% with 0.05% desonide lotion plus moisturising cream, reported as not significant). One subsequent RCT did not report on harms.

Emollients plus potent corticosteroids:

The RCTs gave no information on adverse effects. Other adverse effects of emollients include an occlusion folliculitis on hair bearing skin and anecdotal reports of accidents from slipping while climbing into the bath due to the use of emollient bath additives.

Comment

All of the studies identified by the systematic review were of poor methodological quality. Most RCTs include a mixed population of adults and children, and it is likely that the results can be generalised to both groups.

Clinical guide:

Emollients are almost universally recommended as first line treatment for atopic eczema in adults and children. Emollients vary and long term use is probably governed appropriately by patient preference. Examples include white soft paraffin/liquid paraffin in a 50 : 50 mixture, agents that retain water in the skin such as lactic acid or urea, and aqueous cream. In general, the more oily the preparation, the better and longer lasting the emollient effect. However, adults, and adolescents in particular, often find the most greasy preparations too messy for routine use, especially on the hands and face. Many people prefer to use different emollients for the face and body. Sufficient quantities of emollient should be prescribed to allow it to be applied liberally twice a day. If emollients are being applied to the whole body, children will require up to 250 g a week and adults 500 g a week.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Corticosteroids (alone or used concurrently with emollients)

Summary

SYMPTOM SEVERITY Compared with placebo oil: Moderately potent corticosteroids (0.01% fluocinolone acetonide) in placebo oil may be more effective in clearing atopic eczema at one week compared with placebo oil ( very low-quality evidence ). Mild corticosteroids compared with 1% pimecrolimus: Mild corticosteroids may be more effective compared with 1% pimecrolimus (1% hydrocortisone acetate) in clearing atopic eczema at six months (very low-quality evidence). Potent corticosteroids compared with pimecrolimus: Potent corticosteroids (0.1% betamethasone and 0.1% triamcinolone acetonide) are more effective in clearing atopic eczema at three weeks compared with 1% pimecrolimus ( low-quality evidence ). Mild corticosteroids compared with tacrolimus: Mild corticosteroids (1% hydrocortisone acetate) are less effective in clearing atopic eczema at 3 weeks compared with 0.03% and 0.1% tacrolimus ( high-quality evidence ). Potent corticosteroids compared with tacrolimus: We don’t know if potent corticosteroids are more effective in clearing atopic compared with tacrolimus (low-quality evidence). Mild corticosteroids compared with emollients: Mild corticosteroids (0.05% hydrocortisone cream) may be less effective compared with emollients (kamillosan) in relieving symptoms of atopic eczema ( very low-quality evidence ). Corticosteroids plus emollients compared with emollients: Corticosteroids plus emollients may be more effective in improving symptoms of atopic eczema compared with emollients alone (low-quality evidence). Compared with each other: We don’t know which corticosteroid is more effective in improving disease severity in atopic eczema (very low-quality evidence). Frequency of application: We don't know if a once-daily application of the corticosteroid fluticasone propionate is more effective in clearing atopic eczema or reducing disease severity compared with a twice-daily application (very low-quality evidence). RELAPSE RATES Potent corticosteroids compared with emollients: A potent corticosteroid, fluticasone propionate (0.05%) used intermittently twice a day may be more effective in reducing relapse rates of atopic eczema at 16 weeks compared with emollients (low-quality evidence). Compared with emollients plus corticosteroids: Corticosteroids plus emollients may be more effective in reducing relapse rates compared with emollients alone in atopic eczema (very low-quality evidence). NOTE We found no clinically important results about the effects of mild corticosteroids plus emollients in people with atopic eczema or about the effects of mild corticosteroids compared with pimecrolimus in people with atopic eczema. ADVERSE EFFECTS Corticosteroids are associated with skin burning sensations.

Benefits

We found two systematic reviews (search dates 1999 and 2003), one additional RCT, and five subsequent RCTs. The first systematic review did not include a meta-analysis for clinical outcomes of interest due to poor quality of reporting and scant methodological details, and the second systematic review did not perform a meta-analysis due to heterogeneity of trials.

CLEARANCE: Corticosteroids versus placebo:

We found one systematic review (search date 1999) and one subsequent RCT. The systematic review identified 11 RCTs in children and adults that were found to be of poor methodological quality (see comment). They are not considered further here. The subsequent RCT (94 children aged 2–12 years with active atopic eczema, involving at least 20% of the body surface) found that, compared with peanut oil vehicle, 0.01% fluocinolone acetonide (moderately potent) in peanut oil significantly increased the proportion of people with > 75% clearance at 1 week (> 75% clearance at 1 week: 26.1% with fluocinolone acetonide v 2.3% with peanut oil; p < 0.001, absolute figures not reported). It also found that, compared with peanut oil, 0.01% fluocinolone acetonide in peanut oil significantly increased the proportion of people with > 50% clearance at 1 week (63% with fluocinolone acetonide v 14% with peanut oil; p < 0.001, absolute figures not reported).

Different frequencies of application:

We found one systematic review (search date 2003), which identified seven RCTs. With the exception of two RCTs, the quality of the reporting and of the methods used in these RCTs was generally poor, and therefore five out of the seven RCTs were not further reported. The first RCT identified by the review (unpublished data from Glaxo SmithKline of 248 people aged 1–65 years with moderate/severe atopic eczema) compared once daily application versus twice daily application of 0.005% fluticasone propionate ointment (potent). It found that, compared with twice daily application, once daily application of fluticasone propionate (0.005%) ointment significantly reduced the proportion of people deemed by the physician to show more than 50% improvement by 14% (RR 0.86, 95% CI 0.75 to 0.99, absolute figures not reported). It found similar results for patient assessed improvement, although this did not reach significance (RR 0.87, 95% CI 0.75 to 1.02, absolute figures not reported). The second RCT identified by the review (376 people aged 12–65 years with moderate/severe atopic eczema recruited during an acute flare) had four treatment arms. It compared 0.05% fluticasone propionate cream (potent) once or twice daily versus 0.005% fluticasone propionate ointment (potent) once or twice daily for a 4 week stabilisation phase followed by a 16 week maintenance phase. The proportion of people in remission at the end of the first 4 weeks was not significantly different across the four treatment groups (absent or mild rash on a three item severity score, where 0 = absent, 1 = mild, 2 = moderate, and 3 = severe; remission with fluticasone propionate at 4 weeks: 76/95 [80%] with cream once daily v 76/91 [84%] with cream twice daily v 77/100 [77%] ointment once daily v 64/90 [71%] ointment twice daily; p = 0.546 for 0.05% fluticasone propionate cream once v twice daily and p = 0.249 for 0.005% fluticasone propionate ointment once v twice daily).

MAINTENANCE: Mild corticosteroids versus emollients:

One RCT (72 adults, mean age 45.5 with moderate atopic eczema) compared Kamillosan cream versus 0.5% hydrocortisone cream or vehicle cream. It found that Kamillosan cream improved pruritus, erythema, and desquamation to a slightly greater degree than 0.5% hydrocortisone (significance assessment not performed).

Potent corticosteroids versus emollients:

We found one systematic review (1 RCT) and one additional RCT. Both RCTs found that, compared with emollients alone, 0.05% fluticasone propionate cream used for 2 days each week increased the proportion of people without relapse at 16 weeks (see table 4 ).

Table 4.

RCTs comparing potent corticosteroids versus emollients (see text).

Study	Methods	Participants	Outcomes	Results	Significance
	RCT identified by systematic review. An initial stabilisation phase involved application of 0.05% fluticasone propionate cream or 0.005% ointment once or twice daily until stabilised, and those people who were stabilised went onto a maintenance phase, applying emollients on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo twice weekly	295 adults, aged 12–65 years, with moderate atopic eczema who had been previously stabilised and who later in a 16 week maintenance phase applied0.05% fluticasone propionate cream or 0.005% ointment (potent) twice weekly	Skin redness, hydration, and induration	0.05% fluticasone propionate cream and 0.005% ointment significantly increased the proportion of people without relapse compared with emollients alone at 16 weeks	0.05% fluticasone propionate cream: RR 5.8, 95% CI 3.1 to 10.8, p < 0.001, results presented graphically; 0.005% fluticasone propionate ointment: RR 1.9, 95% CI 1.2 to 3.2, p = 0.010, results presented graphically*
	Additional RCT, which involved an initial stabilisation phase of up to 4 weeks on daily emollients plus fluticasone propionate twice daily. Those participants achieving treatment success entered the double blind maintenance phase, where they continued with regular emollients and were randomised to either intermittent fluticasone propionate or vehicle, once daily for 4 days a week for 4 weeks, followed by once daily 2 days per week for 16 weeks.	231 children and 117 adults, aged 3 months to 65 years, with moderate/severe atopic eczema who had been previously stabilised and who later in a 16 week maintenance phase applied fluticasone propionate 0.05% cream (potent) twice weekly	Skin hydration, lichenification, and erythema	0.05% fluticasone propionate significantly increased the proportion of people without relapse compared with emollients alone at 16 weeks	relapse rate: 58/229 [25.3%] with fluticasone v 79/119 [66.4%] with emollient; OR 7.7 (95% CI 4.6 to 12.8; p < 0.001

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*Participants using fluticasone propionate were advised to apply cream to both known “healed” sites and any newly occurring sites of eczema and improvement in scoring of atopic eczema was measured overall. Therefore, it is uncertain whether improvements in scoring of atopic eczema score were because of prevention of relapse or improvement in newly occurring sites of eczema.

Mild corticosteroids plus emollients:

We found no RCTs of sufficient quality.

Potent corticosteroids plus emollients:

One RCT (91 people with atopic dermatitis, mean age 27 years) found that, compared with a lipid mixture (ceramide-3 and patented nanoparticles) alone, a lipid mixture with topical corticosteroids (selected for each patient on the basis of clinical severity of symptoms) significantly improved erythema (p = 0.041) and overall severity of disease (p = 0.007) at week 4 and pruritus at week 8 (p = 0.018) compared with baseline measures (outcomes measured using a visual 4 point rating scale; results presented graphically).

Corticosteroids versus one another:

We found two RCTs. The first RCT (174 children aged 1–15 years with mild or moderate atopic eczema defined by the Hanifin and Rajka scale) compared 0.1% betamethasone valerate (potent) for 3 days followed by the base ointment for 4 days versus 1% hydrocortisone (mild) applied for 7 days. There was no significant difference between 0.1% betamethasone valerate and 1% hydrocortisone in the number of scratch free days (118 days with 1% hydrocortisone v 117.5 days with 0.1% betamethasone valerate, p = 0.53). The median number of relapses for both groups was one. Both groups showed similar, clinically important (> 20% improvement on the six area, six sign atopic dermatitis severity scale) improvements in disease severity compared with baseline (55% with hydrocortisone v 56% with betamethasone, absolute numbers not reported; p = 1.00). The second RCT (265 children aged 2–14 years with severe atopic eczema) involved two studies of identical design; one comparing 0.05% fluticasone propionate cream (potent) versus 1% hydrocortisone cream (mild) and the other comparing 0.05% fluticasone propionate cream versus 0.1% hydrocortisone butyrate cream (potent). Treatments were applied daily for 2–4 weeks until the atopic eczema was stabilised and thereafter intermittently “as required” (up to twice daily) to affected areas at the first sign of a relapse. It found that, compared with either 1% hydrocortisone cream or 0.1% hydrocortisone butyrate cream, 0.05% fluticasone propionate significantly improved disease severity (total atopic dermatitis score) and reduced relapse rates over 12 weeks (mean atopic dermatitis score in acute phase [0–30, higher is worse]: 7.06 [62 people] with 0.05% fluticasone propionate v 9.45 [65 people] with 1% hydrocortisone cream; p < 0.001; 6.34 [56 people] with 0.05% fluticasone propionate v 7.59 [52 people] with 0.1% hydrocortisone butyrate; p = 0.042); mean atopic dermatitis score in maintenance phase: 5.10 [53 people] with 0.05% fluticasone propionate v 6.98 [54 people] with 1% hydrocortisone cream; p = 0.006; 3.95 [49 people] with 0.05% fluticasone propionate v 5.33 [37 people] with 0.1% hydrocortisone butyrate; p = 0.042).

Mild corticosteroids versus pimecrolimus:

We found no RCTs.

Potent corticosteroids versus pimecrolimus:

See benefits of pimecrolimus.

Potent corticosteroids (trunk) mild corticosteroids (face) versus pimecrolimus:

See benefits of pimecrolimus.

Mild corticosteroids versus tacrolimus:

See benefits of tacrolimus.

Potent corticosteroids versus tacrolimus:

See benefits of tacrolimus.

Potent corticosteroids (trunk) mild corticosteroids (face) versus tacrolimus:

See benefits of tacrolimus.

Harms

Corticosteroids versus placebo:

The systematic review found that studies that specifically gathered data on skin thinning and suppression of the pituitary–adrenal axis failed to find any evidence of harm (figures not reported). Minor adverse effects, such as burning, stinging, irritation, folliculitis, hypertrichosis, contact dermatitis, and pigmentary disturbances, occurred in less than 10% of the people. The subsequent RCT did not report any harms.

Different frequencies of application:

One RCT identified by the review reported no clinically significant skin thinning.

Mild corticosteroids versus emollients:

The RCT gave no information on adverse effects.

Potent corticosteroids versus emollients:

The systematic review did not report on harms. The additional RCT found no clinically significant skin thinning. It also found that fluticasone propionate cream or ointment exerted no significant effect of HPA–axis function during short or longer term treatments (up to 20 weeks).

Corticosteroids versus each other:

The first RCT involved two studies of identical design. In the first study, 20/67 (29%) of people applying 0.05% fluticasone propionate and 21/67 [31%] applying 1.0% hydrocortisone reported adverse events, the most common (> 5%) of which were general symptoms. In the second study, 28/59 (42%) of people applying 0.05% fluticasone propionate and 22/54 (35%) applying 0.1% hydrocortisone butyrate reported adverse events, the most common (> 5%) of which were respiratory tract infection. The second RCT found no clinically significant skin thinning.

Mild corticosteroids plus emollients:

See harms of emollients in self care.

Potent corticosteroids plus emollients:

The RCT gave no information on adverse effects.

Additional studies:

One RCT (658 adults with moderate atopic eczema) compared 1% pimecrolimus cream and topical corticosteroids (potent for limbs and trunk / weak for face) for long term safety and tolerability of unrestricted continuous use for 1 year. It found that 3/330 (1%) people taking topical corticosteroids developed striae and 36/330 (10.9%) burning. Similar studies in children are lacking. One retrospective cohort study (26 boys and 9 girls aged 0.7–18.7 years with atopic eczema) found biochemical evidence of hypothalamic–pituitary–adrenal axis suppression (decreased cortisol response) only in children using potent or very potent topical corticosteroids (as defined by the British National Formulary) or those who had received glucocorticoids from other routes, and not in children who had used mild or moderate topical corticosteroids for a median of 6.9 years.

Comment

Topical steroids versus placebo:

Most of these studies were conducted between 1960 and 1980, when studies of this nature were often poorly designed. Some only reported preference data, making it difficult to interpret the size of effect. Those that did report treatment effect found that is was large. However, none of the studies compared betamethasone 17-valerate versus placebo, despite the fact that this is considered as the standard comparator for new steroids in modern studies. Nearly all studies were of less than 4 weeks' duration. There is insufficient evidence to discern the “best” topical corticosteroid because most trials have only compared one against another, but seldom against the same one and never all together. There is a general lack of industry independent studies comparing topical corticosteroids against each other, and studies are usually too short to inform clinical practice on long term control. Overall, studies found little difference in the number of people responding to treatment between once and twice daily application of potent corticosteroids.

Clinical guide:

In general terms, the lowest potency topical corticosteroid which achieves a good response is used, and the strength of preparation will depend on the age, body site, and severity of lesions to be treated. Because children may be more prone to skin thinning than are adults, particular care is taken to avoid the use of potent preparations to sensitive sites such as the face, axillae, or nappy area. Children may need short bursts of potent corticosteroids to bring their eczema into remission, which is then maintained by emollients and weaker corticosteroid preparations. Adults usually need potent corticosteroids to control eczema on their body and limbs – typically used in short bursts of a few days to a week, followed by a break period when emollients only are used.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Pimecrolimus

Summary

SYMPTOM SEVERITY Compared with placebo: Pimecrolimus may improve clearance of atopic eczema at 3–24 weeks compared with placebo ( moderate-quality evidence ). Compared with mild corticosteroids: 1% pimecrolimus may be less effective compared with a mild corticosteroid (1% hydrocortisone acetate) in clearing atopic eczema at 6 months ( very low-quality evidence ). Compared with potent corticosteroids: 1% pimecrolimus is less effective compared with potent corticosteroids (0.1% betamethasone and 0.1% triamcinolone acetonide) in clearing atopic eczema at 3 weeks ( low-quality evidence ). Compared with tacrolimus: 1% Pimecrolimus is no more effective in clearing atopic eczema at 6 weeks compared with 0.03% tacrolimus (moderate-quality evidence). Frequency of application: Four-times-daily application of pimecrolimus is no more effective in clearing atopic eczema at 3 weeks compared with twice-daily application of pimecrolimus (moderate-quality evidence). Compared with placebo: 1% Pimecrolimus reduces acute flares of atopic eczema as well as the need of corticosteroid rescue treatment at 6–12 months compared with placebo ( high-quality evidence ). ADVERSE EFFECTS Compared with corticosteroids: 1% Pimecrolimus increases skin-burning sensations compared with 0.1% betamethasone valerate or 0.1% triamcinolone acetonide plus hydrocortisone acetate (high-quality evidence). NOTE We found no clinically important results about the effects of pimecrolimus compared with mild corticosteroids in people with atopic eczema. There is a potential cancer risk from the use of pimecrolimus and tacrolimus.

Benefits

We found one systematic review (search date December 2004, 11 RCTs, 2688 people including 437 infants, 1222 children, and 1029 adults), one additional RCT, and one subsequent RCT.

CLEARANCE: Pimecrolimus versus vehicle:

The review found that, compared with vehicle, pimecrolimus increased the proportion of people who were rated by the investigator as clear or almost clear at 3 weeks, 6 weeks, and 6 months, although this did not quite reach significance at 6 months (see table 3 ). One subsequent RCT (196 infants, aged 3–23 months, with mild atopic eczema) found that, compared with vehicle, 1% pimecrolimus cream significantly increased the proportion of people who were rated by the investigator as clear or almost clear at 4 weeks (clear at 4 weeks: 69/130 [53.5%] with pimecrolimus v 7/66 [10.6%] with vehicle; p < 0.001). It found that 1% pimecrolimus significantly reduced pruritis and sleep loss compared with vehicle at 4 weeks (mean pruritis score: 5.1 at baseline v 2.1 at day 29 with pimecrolimus v 4.5 at baseline to 5.2 at day 29 with vehicle; p < 0.001 for the between group comparison).

Table 5.

Systematic review of RCTs comparing pimecrolimus versus vehicle (see text).

Participants	Outcomes	Results
300 infants, aged 2–23 months, 4 RCTs, 205 children, aged 2–26 years, 130 adults with mild to severe eczema	clear at 3 weeks	169/506 [33.4%] with pimecrolimus v 29/277 [10.5%] with vehicle, RR 2.72, 95% CI 1.84 to 4.03
300 infants, aged 2–23 months, 3 RCTs, 205 children, aged 2–26 years, with mild to severe eczema	clear at 6 weeks	160/390 [41.0%] with pimecrolimus v 40/199 [20.1%] with vehicle, RR 2.03, 95% CI 1.50 to 2.74
251 infants, aged 3–23 months, 1 RCT, 251 infants aged 3–23 months with mild to severe eczema	clear at 6 months	138/204 [67.6%] v 14/46 [30.4%] RR 1.46, 95% CI 0.98 to 2.19

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Pimecrolimus versus mild corticosteroid:

We found no systematic reviews or RCTs comparing pimecrolimus with a mild corticosteroid alone.

Pimecrolimus versus potent corticosteroid:

One RCT identified by the review (87 adults, aged 18–71 years) found that, compared with 0.1% betamethasone valerate, pimecrolimus significantly reduced the proportion of people who were rated by the investigator as clear or almost clear at 3 weeks (5/45 [11.1%] with pimecrolimus v 21/42 [50%] with betamethasone valerate; RR 0.22, 95% CI 0.09 to 0.54).

Pimecrolimus versus potent corticosteroid (trunk) and mild corticosteroid (face):

Another RCT identified by the review (658 adults aged 18–79 years with moderate/severe atopic eczema) found that, compared with a combined topical corticosteroid regimen (0.1% triamcinolone acetonide for the trunk and limbs, and 1% hydrocortisone acetate for the face, neck, and intertriginous areas), 1% pimecrolimus significantly reduced the proportion of people rated by the investigator as clear or better after 1 week, 3 weeks, and 6 months of treatment. However, treatment groups did not differ significantly at the end of the trial (12 months). A large number of people in the pimecrolimus arm of the study did not complete it (only 135/328 [41%]). These data are unlikely to inform clinical decisions because the population studied had moderate to severe disease, and pimecrolimus is indicated for mild to moderate disease.

Pimecrolimus versus tacrolimus:

One RCT identified by the review (141 children, aged 2–17 years, with moderate atopic eczema) found no significant difference between 1% pimecrolimus and 0.03% tacrolimus in the proportion of children clear or almost clear at 6 weeks (21/71 [29.6%] with pimecrolimus v 29/70 [41.4%] with tacrolimus; RR 0.71, 95% CI 0.45 to 1.12; p = 0.15).

Different frequencies of application:

One crossover RCT identified by the review (49 adults and children over the age of 10 years with moderate/severe atopic eczema) found no significant difference in the proportion of people clear or almost clear between four times daily application versus twice daily application of 1% pimecrolimus cream at 3 weeks (RR 0.96, 95% CI 0.4 to 2.33).

MAINTENANCE:

Three RCTs identified by the review (1156 people: 251 infants aged 3–23 months; 713 children and young people aged 2–17 years; 192 adults; children with mild to severe, and adults moderate to severe eczema) found that, compared with vehicle, 1% pimecrolimus significantly reduced the proportion of people with a flare of atopic eczema at 6 months and 12 months (flare at 6 months: 3 RCTs, RR 1.92, 95% CI 1.56 to 2.36; flare at 12 months: 2 RCTs, RR 1.84, 95% CI 1.50 to 2.24, absolute figures not reported). The two RCTs that extended to 12 months allowed use of corticosteroids as rescue medication and both found that the proportion of people requiring corticosteroids was significantly reduced at 6 and 12 months compared with vehicle (corticosteroid use at 6 months: 2 RCTs, RR 1.82, 95% CI 1.51 to 2.21; corticosteroid use at 12 months: 2 RCTs, RR 1.82, 95% CI 1.52 to 2.18, absolute figures not reported). One additional RCT (130 adults; median age 27 years, range 18–65, with moderate atopic eczema) found that 1% pimecrolimus reduced the number of days of rescue corticosteroids required compared with a vehicle cream (9.7% with pimecrolimus v 37.8% with vehicle; p < 0.001, absolute figures not reported). It also reported changes in two quality of life measures (the Quality of life Index – Atopic Dermatitis and Dermatology Life Quality Index). It found that, compared with vehicle, pimecrolimus significantly increased perceived quality of life (mean improvement in the Quality of life Index – Atopic Dermatitis score: 25.5% with pimecrolimus v 2.1% with vehicle, p = 0.002; mean improvement in Dermatology Life Quality Index score: 22.9% with pimecrolimus v 0.9% with vehicle, p = 0.007, absolute figures not reported for either outcome).

Harms

The systematic review found no significant difference in the incidence of skin burning for 1% pimecrolimus and vehicle (6 RCTs, 204/1166 [17.5%] with pimecrolimus v 131/579 [22.6%] with vehicle; RR 0.87, 95% CI 0.07 to 1.09). However, 1% pimecrolimus significantly increased skin burning compared with both 0.1% betamethasone valerate and a combined regimen of 0.1% triamcinolone acetonide plus hydrocortisone acetate (skin burning: 1/43 [2.3%] with pimecrolimus v 2/45 [4.4%] with betamethasone valerate; RR 0.52, 95% CI 1.92 to 14.30, p < 0.05; 85/328 [25.9%] with pimecrolimus v 36/330 [10.9%] with triamcinolone acetonide plus hydrocortisone acetate; RR 2.38, 95% CI 1.66 to 3.40, p < 0.05).

Harms alerts:

The United States Food and Drug Administration issued a public health advisory to inform people about a potential cancer risk from the use of pimecrolimus and tacrolimus. This concern is based on information from animal studies, case reports in a small number of people, and knowledge of how drugs in this class work. It may take human studies of 10 years or longer to determine if use of pimecrolimus or tacrolimus is linked to cancer. In the meantime, this risk is uncertain, and the United States Food and Drug Administration advises that pimecrolimus and tacrolimus should be used only as labelled, after other prescription treatments have failed to work or cannot be tolerated.

Comment

Pimecrolimus has been found to be less effective than 0.1% betamethasone valerate (potent topical corticosteroid). The efficacy of pimecrolimus compared with less potent steroids is not known. In practice, pimecrolimus is being aimed at people with mild atopic eczema; however, this is being done in the absence of RCTs that compare it with existing therapy for such a group. Pimecrolimus prevented more flares than vehicle; however, it is not known if early use of mild topical corticosteroids may be as effective.

Clinical guide:

The UK National Institute of Health and Clinical Excellence recommends that topical pimecrolimus is used as a second line option for resistant head and neck eczema. It may be used in children (over the age of 2 years) and adults, and may be useful for people who become dependent on topical corticosteroids at sensitive sites such as the face, where there is a significant risk of skin thinning. Pimecrolimus is licensed as a second line agent in the USA, although the site of application is not restricted for pimecrolimus.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Tacrolimus

Summary

SYMPTOM SEVERITY Compared with placebo: Tacrolimus 0.03% and 1% are more effective at clearing atopic eczema compared with placebo ( high-quality evidence ). Compared with a mild corticosteroid: 0.03% and 0.1% tacrolimus are more effective compared with mild corticosteroids (1% hydrocortisone acetate) in clearing atopic eczema at 3 weeks (high-quality evidence). Compared with potent corticosteroids: We don’t know if tacrolimus is more effective in clearing atopic eczema compared with potent corticosteroids ( low-quality evidence ). Compared with Pimecrolimus: 0.03% tacrolimus is no more effective in clearing atopic eczema at 6 weeks compared with 0.1% pimecrolimus ( moderate-quality evidence ). Comparing 0.03% with 0.1% tacrolimus: Tacrolimus 0.03% may be as effective as tacrolimus 0.1% in clearing atopic eczema at 3 weeks but may be less effective at 12 weeks (low-quality evidence). ADVERSE EFFECTS Tacrolimus 0.03% and tacrolimus 0.1% increase skin-burning sensations compared with vehicle (high-quality evidence). QUALITY OF LIFE Compared with vehicle: 0.03% and tacrolimus 0.1% are effective in improving quality of life at 12 weeks in toddlers, children, and adults, compared with vehicle (high-quality evidence). NOTE There is a potential cancer risk from the use of pimecrolimus and tacrolimus.

Benefits

We found one systematic review (search date December 2004, 14 RCTs, 4209 people with moderate to severe atopic eczema, including 2712 adults and 1497 children).

Tacrolimus versus vehicle:

One RCT identified by the review (136 children, aged 7–16 years, with moderate/severe atopic eczema) found that, compared with vehicle, 0.03% tacrolimus significantly improved the proportion of people with at least 90% symptom improvement, as assessed by physicians at 3 weeks (physicians' global assessment of 90% improvement or better: 25/44 [56.8%] with tacrolimus v 12/44 [27.3%] with vehicle; RR 2.13, 95% CI 1.24 to 3.68, p = 0.006). It also found that both 0.03% and 0.1% tacrolimus significantly improved the proportion of people who rated their response as better or much better compared with vehicle at 3 weeks (improvement with 0.03% tacrolimus: RR 1.47, 95% CI 1.06 to 2.04; improvement with 0.1% tacrolimus: RR 1.76, 95% CI 1.13 to 2.36, absolute figures not reported). Three further RCTs identified by the review (656 people, including 234 children aged 2–15 years, and 423 adults with mild atopic eczema) found that, compared with vehicle, both 0.03% and 0.1% tacrolimus significantly increased the proportion of people rated by the investigator as clear or achieving excellent improvement (improvement with 0.03% tacrolimus: 100/328 [30.5%] with tacrolimus v 22/328 [6.7%] with vehicle; RR 4.50, 95% CI 2.91 to 6.96, p < 0.0001; improvement with 0.1% tacrolimus: 125/327 [38.2%] with tacrolimus v 22/328 [6.7%] with vehicle; RR 5.62, 95% CI 3.67 to 8.61, p < 0.0001).

Tacrolimus versus mild corticosteroid:

We found one systematic review (3 RCTs). Two RCTs identified by the review (1183 children, aged 2–15 years, with moderate/severe atopic eczema) found that, compared with 1% hydrocortisone acetate, both 0.03% and 0.1% tacrolimus significantly increased the proportion of people rated as clear or achieving excellent improvement on the modified eczema area and severity index at 3 weeks (149/399 [37.3%] with 0.03% tacrolimus v 57/391 [14.6%] with hydrocortisone acetate; RR 2.56, 95% CI 1.95 to 3.36 and 89/186 [47.9%] with 0.1% tacrolimus v 29/185 [15.7%] with hydrocortisone acetate; RR 3.05, 95% CI 2.12 to 4.40). Another small RCT identified by the review (143 adults with moderate/severe atopic eczema) found that, compared with 0.1% aclometasone dipropionate, 0.1% tacrolimus significantly increased the proportion of people achieving at least marked improvement > 75% for treating facial atopic eczema at 1 week (RR 3.94, 95% CI 2.21 to 7.0, absolute figures not reported).

Tacrolimus versus potent corticosteroid:

One RCT identified by the review (570 adults, aged 16–70 years, with moderate/severe atopic eczema) found that, compared with 0.1% hydrocortisone butyrate, 0.03% tacrolimus significantly decreased the proportion of people achieving excellent improvement at 3 weeks (71/193 [36.8%] with 0.03% tacrolimus v 94/186 [50.5%] with 0.1% hydrocortisone butyrate, RR 0.73, 95% CI 0.58 to 0.92). However, there was no significant difference between 0.1% tacrolimus twice daily and 0.1% hydrocortisone butyrate in the proportion of people achieving excellent improvement at 3 weeks (92/191 [48.1%] with 0.1% tacrolimus v 94/186 [50.5%] with 0.1% hydrocortisone butyrate; RR 0.95, 95% CI 0.78 to 1.17).. One RCT identified by the review (181 adults with moderate to severe atopic eczema) found no significant difference between 0.1% tacrolimus twice daily and 0.12% betamethasone valerate in the proportion of people with at least marked improvement at 3 weeks (> 75% on physicians' global assessment; pooled RR for both RCTs 1.08, 95% CI 0.97 to 1.21).

Tacrolimus versus potent corticosteroid (trunk) and mild corticosteroid (face):

One RCT identified by the review (968 adults with moderate/severe atopic eczema) found that, compared with a combined topical corticosteroid regimen (0.1% hydrocortisone butyrate for trunk and extremities plus 1% hydrocortisone acetate for head and neck), 0.1% tacrolimus significantly increased the proportion of people clear or achieving excellent improvement at 12 weeks (231/484 [47.7%] v 138/484 [28.5%]; RR 1.67, 95% CI 1.41 to 1.98, p < 0.0001).

0.03% Tacrolimus versus 0.1% tacrolimus:

Six RCTs identified by the review compared 0.03% tacrolimus with 0.1% tacrolimus. Pooled analysis for three RCTs (696 children aged 2–17 years, 570 adults with moderate to severe atopic eczema) found no significant difference between 0.03% and 0.1% tacrolimus in people clear or achieving an excellent improvement at 3 weeks (168/423 [39.7%] with 0.03% tacrolimus v 202/424 [47.6%] with 0.1% tacrolimus; RR 0.89, 95% CI 0.67 to 1.19). The other three RCTs (351 children, aged 2–25 years, 205 adults with moderate to severe atopic eczema) could not be pooled because of different outcome measures. The RCTs found that, compared with 0.03% tacrolimus, 0.1% tacrolimus significantly increased the proportion of people clear or achieving an excellent improvement at 12 weeks (100/328 [30.5%] with 0.03% tacrolimus v 125/327 [38.2%] with 0.1% tacrolimus; RR 0.80, 95% CI 0.65 to 0.99). The review found that there was no significant difference between 0.03% tacrolimus and 0.1% tacrolimus in participants' global assessment of response (better or much better) at 3 weeks and 12 weeks (3 weeks: 0.84, 95% CI 0.69 to 1.00; 12 weeks: 0.93, 95% CI 0.83 to 1.03, absolute figures not reported).

Tacrolimus versus pimecrolimus:

See benefits of pimecrolimus.

Quality of life:

One study identified by the systematic review comprised three separate RCTs assessing quality of life in three populations: adults, children, and toddlers (using the dermatology life quality index in adults, the children's dermatology life quality index, and a modified version of this instrument in toddlers). It found that both 0.03% and 0.1% tacrolimus significantly improved quality of life at 12 weeks (985 people, 50% of children and adults, and two thirds of children with severe atopic eczema, with similar baseline quality of life scores in each age group; mean change in quality of life change scores [adults]: –5.6 with vehicle v –21.1 with 0.03% tacrolimus v –27.1 with 0.1% tacrolimus; p < 0.005 for all comparisons; [children]: –8.1 with vehicle v –24.4 with 0.03% tacrolimus v –24.1 with 0.1% tacrolimus; p < 0.000 for both doses of tacrolimus versus vehicle; [toddlers]: –7.9 with vehicle v –30.8 with 0.03% tacrolimus v –35.6 with 0.1% tacrolimus; p < 0.000 for both doses of tacrolimus versus vehicle). It also found that, compared with 0.03% tacrolimus, 0.1% tacrolimus significantly improved quality of life in adults (p < 0.000). No significant difference was found between 0.03% and 0.1% tacrolimus in quality of life in infants or children (p = 0.937 in children; p = 0.224 in toddlers).

Harms

The systematic review found that, compared with vehicle, 0.03% and 0.1% tacrolimus significantly increased the proportion of people with skin burning (0.03% tacrolimus: 173/425 v 92/426; RR 1.89, 95% CI 1.43 to 2.50; 0.1% tacrolimus: 187/430 v 90/426, RR 2.08, 95% CI 1.35 to 3.18). Both doses were also significantly more likely to cause skin burning than were mild or potent topical corticosteroids (see table 1 ). The incidence of skin infection was not significantly different in any of the comparisons of pimecrolimus or tacrolimus with active or vehicle control (see table 1 ).

Harms alerts:

The United States Food and Drug Administration issued a public health advisory to inform people about a potential cancer risk from the use of pimecrolimus and tacrolimus. This concern is based on information from animal studies, case reports in a small number of people, and knowledge of how drugs in this class work. It may take human studies of 10 years or longer duration to determine if use of pimecrolimus or tacrolimus is linked to cancer. In the meantime, this risk is uncertain, and the United States Food and Drug Administration advises that pimecrolimus and tacrolimus should be used only as labelled, for people after other prescription treatments have failed to work or cannot be tolerated.

Comment

Clinical guide:

0.1% tacrolimus may be as effective as potent topical corticosteroids and more effective than mild topical corticosteroids. Similarly to pimecrolimus, tacrolimus preparations are only used as second line treatments for children and adults with atopic eczema because of their unknown long term side effects. Topical tacrolimus may be useful for resistant atopic eczema at sensitive sites such as the face, where the use of more potent topical steroids carries a high risk of thinning of the skin and telangiectasia. 0.1% tacrolimus may be useful for people (children and adults) who depend on constant use of potent steroids, although currently there is no evidence on how effective it is in such a subgroup of treatment “failures”.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Vitamin E and multivitamins

Summary

DISEASE SEVERITY Vitamin E plus vitamin B, compared with Vitamins E and B alone: Vitamin E plus Vitamin B2 may be more effective in reducing disease severity of atopic eczema at 4 weeks compared with vitamins E or B alone ( very low-quality evidence ). Vitamin E compared with placebo or selenium: We don't know if Vitamin E is more effective in reducing disease severity at 12 weeks to 8 months compared with placebo or selenium (very low-quality evidence).

Benefits

We found one systematic review (search date 1999, 2 RCTs) and one subsequent RCT. The first RCT identified by the review (60 adults with moderate/severe atopic eczema) had three arms: selenium (600 ìg) alone versus selenium (600 ìg) plus vitamin E (600 IU) versus placebo over 12 weeks. It found no significant difference between selenium alone, selenium plus vitamin E, and placebo in mean severity score (mean severity score assessed using several skin signs at several body sites [0–30, higher is worse]: 21.0 at baseline to 13.7 with selenium v 21.8 at baseline to 15.3 with selenium plus vitamin E v 20.4 at baseline to 14.5 with placebo; reported as not significant). The second RCT identified by the review (59 people with mild/moderate atopic eczema of the dry type) also had three arms: vitamin E (100 mg) alone versus vitamin B2 (20 mg riboflavin butyrate) alone versus vitamin E plus vitamin B2 over 4 weeks. It found that, compared with vitamin E or vitamin B2 alone, vitamin E plus vitamin B2 significantly increased the proportion of people with an improved physicians' global assessment at 4 weeks (significance assessment not performed). However, the clinical significance of these results is difficult to interpret in the absence of a placebo. One subsequent RCT (96 adults and children, aged 10–60 years, with moderate/severe atopic eczema involving 30–70% of the body surface) compared vitamin E supplementation versus placebo over 8 months. The clinical assessment of pruritus was performed using the SCORing Atopic Dermatitis index. It found that, compared with placebo, vitamin E significantly improved the proportion of people with “great improvement” (23/50 [46%] with vitamin E versus 1/46 [2.2%] with placebo; significance assessment not performed). It also found that, compared with placebo, vitamin E increased the proportion of people who went into almost complete remission (7/50 [14%] with vitamin E v 0/46 [0%] with placebo).

Harms

The RCTs did not report on harms.

Comment

It is likely that the results are generalisable to both adults and children.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Egg and cow's milk exclusion diet

Summary

DISEASE SEVERITY Hydrolysed cows' milk formula compared with an amino acid-based formula: Hydrolysed cows' milk formula may be as effective as an amino acid-based formula in reducing the severity of atopic eczema in infants with proven cows' milk intolerance at 6 months ( very low-quality evidence ).

Benefits

We found one systematic review (search date 1999, 5 RCTs) and one subsequent RCT. The review considered the interventions and study populations too diverse to warrant statistical pooling, and raised serious methodological concerns, such as poor concealment of randomisation allocation, lack of blinding, and high withdrawal rates without an intention to treat analysis. The results are not considered further here. One subsequent RCT (73 infants, aged 1–10 months, with a cow's milk allergy/intolerance, proven by double blind, placebo controlled food challenge) compared extensively hydrolysed cow′s milk formula with an amino acid based formula. It found that, compared with baseline, both groups improved the SCORing Atopic Dermatitis index score in all children at 6 months (mean SCORing Atopic Dermatitis index score for both formulas: 24.6, 95% CI 20.1 to 29.0 at baseline v 10.7, 95% CI 7.1 to 14.2 at 6 months, p < 0.0001). The RCT did not perform a comparison between groups.

Harms

Calcium, protein, and calorie deficiency are always a risk in dairy free diets in children. Three RCTs used potentially allergenic soya based milk substitute, which itself can be allergenic in atopic eczema.

Comment

The clinical importance of changes in severity scores obtained in many studies is unknown. Drop out rates are particularly high for elimination diets and those containing hydrolysate milk substitutes.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Probiotics

Summary

DISEASE SEVERITY Compared with placebo: Lactobacillus may be no more effective in reducing total eczema severity at 6 weeks compared with placebo ( very low-quality evidence ). ADVERSE EFFECTS Heat inactivated, but not viable, lactobacillus may increase episodes of diarrhoea in infants.

Benefits

One weak crossover RCT (58 children, aged 1–13 years, with atopic eczema) found that, compared with placebo, Lactobacillus (2 strains) decreased the total eczema severity (as measured by the SCORing Atopic Dermatitis scale) at 6 weeks, although this did not reach significance (mean SCORing Atopic Dermatitis index with lactobacillus: 35.6 at baseline v 31.6 at 6 weeks; p = 0.06; SCORing Atopic Dermatitis index with placebo reported as “unchanged”; between group comparison not reported). Lactobacillus increased the proportion of people who perceived their eczema to have improved compared with placebo (56% with lactobacillus v 15% with placebo; p = 0.001, absolute figures not reported).

Harms

Recruitment in one RCT was prematurely terminated due to adverse gastrointestinal symptoms. It found that, compared with viable Lactobacillus GG and placebo, heat inactivated lactobacillus GG increased the proportion of infants with diarrhoea from several days to weeks after formula introduction (5/13 [38.5%] with inactivated lactobacillus GG v 0/17 [0%] with viable lactobacillus GG v 0/10 [0%] with placebo). No adverse reactions were reported in the other groups. The crossover RCT did not report on harms.

Comment

At the time of review, there was no convincing RCT evidence that probiotic treatment helps children with established atopic eczema. Future studies should involve comparisons between specific age groups, and people should be stratified according to allergic sensitization or total immunoglobulin E level. Recent RCTs performed after the search for this review seem to suggest that probiotics may reduce eczema severity, and will be reviewed fully in the next update.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Few foods diet

Summary

DISEASE SEVERITY Compared with usual diets: Few-foods diet plus whey or casein hydrolysates may be less effective in reducing eczema severity at 6 weeks compared with usual diets ( very low-quality evidence ). NOTE Elemental or few-foods diets are difficult to follow and are unpalatable.

Benefits

We found one systematic review (search date 1999, 1 RCT). The RCT (85 children, aged 0.3–13.3 years) identified by the review compared a few foods diet (eliminating all but 5–8 foods) plus whey hydrolysate versus a few foods diet plus casein hydrolysate versus a usual diet for 6 weeks. It found that, compared with usual diet, both few foods diets reduced the proportion of people who had more than 70% improvement in skin severity score (16/22 [73%] with usual diet v 15/24 [58%] with few foods diet; reported as significant). A total of 35 out of the 39 withdrawals were in the diet group, illustrating the difficulty of adopting a few foods diet, even in motivated people. The analysis was not by intention to treat.

Harms

The systematic review did not report on harms.

Comment

Clinical guide:

At present, there is no RCT evidence to support the use of an elemental or few foods diet; both diets are difficult to follow and are unpalatable. In addition, elemental diets appear to be impractical and require hospitalisation.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Elemental diet

Summary

We found no direct information about whether elemental diets are better than no active treatment in people with atopic eczema. Elemental or few-foods diets are difficult to follow and are unpalatable.

Benefits

We found no systematic review or RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Zinc supplementation

Summary

DISEASE SEVERITY Compared with placebo: Zinc sulphate supplements are no more effective than placebo in reducing disease severity scores of atopic eczema at 8 weeks ( moderate-quality evidence ).

Benefits

We found one RCT (50 children, aged 1–16 years), which compared zinc sulphate (185.4 mg per day) with placebo. It found no significant difference in combined disease severity score between zinc sulphate and placebo (mean combined disease severity score [0–70, higher is worse]: 36.1 at baseline v 48.7 at 8 weeks with zinc sulphate compared with 34.6 at baseline v 39.3 at 8 weeks with placebo; p = 0.64 for between group comparison).

Harms

The RCT found that six people stopped taking the capsules, one (placebo) due to loose stools, one (zinc sulphate) due to severe exacerbation of eczema (attributed to the capsules by the parent), three (one zinc, 2 placebo) developed a widespread itchy maculopapular rash 6–15 days after starting treatment, and one (placebo) developed a herpes simplex virus skin infection recurrence.

Comment

None.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Pyridoxine (vitamin B6)

Summary

DISEASE SEVERITY Compared with placebo: Pyridoxine (vitamin B6) may be no more effective than placebo in reducing disease severity scores of atopic eczema at 4 weeks ( low-quality evidence ).

Benefits

We found one systematic review (search date 1999, 2 RCTs). The first study identified by the review was too small to be considered. The second RCT identified by the review (48 children with moderate/severe atopic eczema) found no significant difference between pyridoxine and placebo in skin severity score at 4 weeks (median skin severity score [total area affected × overall degree of erythema, with a possible range 0–500] 92.3 at baseline to 109.0 with pyridoxine v 125.5 at baseline to 77.0 with placebo; reported as not significant).

Harms

One child developed a non-specific erythematous rash while taking pyridoxine.

Comment

There is insufficient RCT evidence to support the benefit of pyridoxine in the treatment of atopic eczema.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Essential fatty acids (evening primrose oil, blackcurrant seed oil, fish oil)

Summary

DISEASE SEVERITY Compared with placebo: Essential fatty acids (evening primrose oil, blackcurrant seed oil, borage oil, or fish oil) may be no more effective than placebo in reducing disease severity scores of atopic eczema ( low-quality evidence ).

Benefits

We found one systematic review (search date April 2002, 20 RCTs, 1357 people, aged 0.6–78 years, including 6 RCTs in adults only [293 adults], 9 RCTs in adults and children [679 people], 5 RCTs in children [385 people]) and one subsequent RCT. Effect size could not be calculated for 8 studies due to insufficient data on overall severity or component subscales of atopic eczema. The review found no significant difference between essential fatty acids (evening primrose oil, borage oil, blackcurrant seed oil, fish oil) and placebo in physician assessed overall severity (see table 4 ) The subsequent RCT found no significant difference in mean improvement in eczema between borage oil capsules (920 mg gamma linolenic acid) and placebo in at 12 weeks (see table 4 ).

Table 6.

RCTs comparing essential fatty acids versus placebo (see text)

Study	Methods	Participants	Outcomes	Results
	Systematic review pooled data: five RCTs for borage oil, 11 RCTs, and one controlled clinical trial of evening primrose oil, one RCT of blackcurrant seed oil and four RCTs and one controlled clinical trial of fish oil.	3 RCTs (243 adults), 4 RCTs (159 children), 4 RCTs (299 adults and children)	Pooled effect size for evening primrose oil and borage seed oil	+ 0.15, 95% CI –0.02 to + 0.32; p = 0.09
	Systematic review pooled data: five RCTs for borage oil, 11 RCTs, and one controlled clinical trial of evening primrose oil, one RCT for blackcurrant seed oil and four RCTs and one controlled clinical trial of fish oil.	2 RCTs (176 adults), 1 RCT in 82 adults and children	Pooled effect size for fish oils	–0.01, 95% CI –0.27 to + 0.30; p value not reported
	Borage oil capsules (920 mg gamma linolenic acid) versus placebo over 12 weeks	151 participants including 69 children	Mean physician assessed improvement in eczema (SASSAD score)	+ 1.4, 95% CI –2.2 to + 5.0; p = 0.45

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Harms

The systematic review did not report on harms. The subsequent RCT found lower rates of adverse events with borage oil compared with placebo (diarrhoea: 6/85 [4%] with borage oil v 6/55 [11%] with placebo; nausea, vomiting, or both: 3/85 [4%] with borage oil v 5/55 [9%] with placebo; headache: 1/85 [1%] with borage oil v 4/55 [7%] with placebo; influenza like symptoms: 22/85 [26%] with borage oil v 21/55 [38%] with placebo; significance assessment not performed).

Comment

Borage oil, blackcurrant oil, and evening primrose oil are all sources of gamma linolenic acid. It is likely that the results are generalisable to both adults and children.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Prolonged breast feeding by mother straight after birth

Summary

We found no direct information on the effects of breast feeding straight after birth on the development of atopic eczema in infants. DEVELOPMENT OF ATOPIC ECZEMA Compared with bottle feeding: Breast feeding may reduce the risk of developing eczema compared with bottle feeding ( very low-quality evidence ).

Benefits

We found no systematic review or RCTs.

Harms

We found no RCTs.

Comment

We found one systematic review (search date May 2000, 14 prospective cohort studies, 4158 people), which did not meet the inclusion criteria for this review. The summary odds ratio for the protective effect of breast feeding (in children with a family history of atopy) was 0.58, 95% CI 0.41 to 0.9. Much of the available evidence was limited by weak methods (e.g. selection and information bias, short duration of breast feeding, and inadequate control for confounding factors, such as introducing supplemental milk or solid foods). Prolonged self selected breast feeding may be associated with unknown protective factors, leading to bias. It is unlikely that an RCT will be conducted in this area, for ethical reasons.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Reducing allergens (maternal dietary restriction, control of house dust mite only)

Summary

DEVELOPMENT OF ATOPIC ECZEMA Maternal antigen avoidance diet compared with normal diet: We don’t know whether maternal antigen avoidance diets during pregnancy or lactation are effective in reducing the incidence of infants developing atopic eczema during their first 12–18 months of life compared with normal diets ( very low-quality evidence ). Mite reduction compared with information: Mite reduction using an impermeable mattress cover for the child’s bed is no more effective at reducing the incidence of children developing atopic eczema at 24 months compared with advice for allergen avoidance, or information on allergies ( moderate-quality evidence ) NOTE Maternal antigen avoidance diets may decrease mean gestational weight gain by 1.8 kg for a 60 kg woman, and may be associated with a higher risk of preterm birth.

Benefits

Maternal dietary restriction:

We found one systematic review (search date October 2002, 4 RCTs, 451 pregnant women on antigen avoidance diet during pregnancy). RCTs identified by the review were found to be of poor methodological quality, with the exception of one. One RCT did not include the number of women randomised and so was not included in the meta-analysis. The review found no significant difference between maternal antigen avoidance and no avoidance during pregnancy on the incidence of atopic eczema during the first 12–18 months of life (3 RCTs, 47/177 [26.6%] with avoidance v 52/195 [26.7%] with no avoidance; RR 0.94, 95% CI 0.67 to 1.33). The systematic review also included three trials of antigen avoidance during lactation (210 lactating women). The methodological quality of these trials was also poor and two of the studies began the diet during pregnancy. Randomisation was unclear for all of the studies, and analysis was not based on intention to treat. Only one study gave details of compliance and blinding of the physicians who examined the children for atopic eczema. The review found that, compared with no avoidance, maternal antigen avoidance reduced the proportion of children developing atopic eczema during their first 12–18 months of life (3 RCTs, 21/96 [20.1%] with avoidance v 40/98 [39.2%] with no avoidance; RR 0.56, 95% CI 0.36 to 0.86).

House dust mite reduction:

We found one RCT (696 newborn children, at high risk of developing allergies). It found no significant difference in the development of eczema between use of a mite impermeable mattress encasing for the child's bed versus a simple educational package on allergen avoidance versus basic information about allergies at 24 months.

Harms

Maternal dietary restriction:

One RCT identified by the review found that, compared with no avoidance, maternal antigen avoidance significantly decreased mean gestational weight gain by a small amount (WMD: –3.0, 95% CI –5.21 to –0.79, percentage of pre-pregnancy weight [i.e. 1.8 kg for a 60 kg woman]).

House dust mite reduction:

The RCT gave no information on adverse effects.

Comment

More data are necessary on potential adverse effects of maternal antigen avoidance on gestational weight gain, fetal growth, and preterm birth.

Clinical guide:

Antigen avoidance diets for women during pregnancy with a history of atopy are unlikely to substantially reduce her risk of giving birth to an atopic child. House dust mite avoidance did not show a protective effect on the development of sensitisation to house dust mites or symptomatic allergy in children at 24 months. Maternal antigen avoidance diets during lactation may substantially reduce the child's risk of developing atopic eczema; however, existing data must be interpreted with caution due to the poor methodological quality of these studies.

Substantive changes

BMJ Clin Evid. 2006 Jul 1;2006:1716.

Early introduction of probiotics (in last trimester or shortly after birth)

Summary

DEVELOPMENT OF ATOPIC ECZEMA Early introduction of probiotics compared with placebo: The Probiotic lactobacillus GG, taken 2– 4 weeks before delivery and for 6 months after birth, reduces the number of infants who develop atopic eczema at 24 months to 4 years compared with placebo ( low-quality evidence ).

Benefits

One RCT (159 mothers with at least one first degree relative or partner with atopic eczema) compared two capsules of Lactobacillus GG daily (1 × 10¹⁰ colony forming units) versus placebo for 2–4 weeks before delivery and for 6 months afterwards. After delivery, either the breastfeeding mothers or the infants could take the capsules. It found that, compared with placebo, Lactobacillus GG significantly decreased the proportion of infants who developed atopic eczema at 24 months by half (15/64 [23%] with lactobacillus GG v 31/68 [46%] with placebo; RR 0.51, 95% CI 0.32 to 0.84). A follow up RCT found that this was maintained at 4 years (14/53 [26.4%] with Lactobacillus v 25/54 [46.3%] with placebo; RR 0.57, 95% CI 0.33 to 0.97).

Harms

The RCT gave no information on adverse effects.

Comment

Evidence from one study suggests that probiotic Lactobacillus GG, when taken by women during pregnancy and then either continued during breast feeding or given to the baby, may help in prevention of early atopic disease in children at high risk. It also appears that the preventive effect of Lactobacillus GG on atopic eczema extends beyond infancy.

Substantive changes

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PERMALINK

Eczema (atopic)

Fiona Bath-Hextall

Hywel Williams

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

About this condition

Definition

Table 1.

Table 2.

Incidence/ Prevalence

Aetiology/ Risk factors

Prognosis

Aims of intervention

Outcomes

Methods

Table.

Glossary

Disclaimer

Contributor Information

References

Emollients (alone or plus topical steroids)

Summary

Benefits

Emollient versus placebo:

Table 3.

Emollients versus each other:

Emollients versus mild corticosteroid:

Emollients versus potent corticosteroid:

Emollients plus mild corticosteroid:

Emollients plus potent corticosteroid:

Harms

Emollients versus placebo:

Emollients versus each other:

Emollients versus mild corticosteroids:

Emollients versus potent corticosteroids:

Emollients plus mild corticosteroids:

Emollients plus potent corticosteroids:

Comment

Clinical guide:

Substantive changes

Corticosteroids (alone or used concurrently with emollients)

Summary

Benefits

CLEARANCE: Corticosteroids versus placebo:

Different frequencies of application:

MAINTENANCE: Mild corticosteroids versus emollients:

Potent corticosteroids versus emollients:

Table 4.

Mild corticosteroids plus emollients:

Potent corticosteroids plus emollients:

Corticosteroids versus one another:

Mild corticosteroids versus pimecrolimus:

Potent corticosteroids versus pimecrolimus:

Potent corticosteroids (trunk) mild corticosteroids (face) versus pimecrolimus:

Mild corticosteroids versus tacrolimus:

Potent corticosteroids versus tacrolimus:

Potent corticosteroids (trunk) mild corticosteroids (face) versus tacrolimus:

Harms

Corticosteroids versus placebo:

Different frequencies of application:

Mild corticosteroids versus emollients:

Potent corticosteroids versus emollients:

Corticosteroids versus each other:

Mild corticosteroids plus emollients:

Potent corticosteroids plus emollients:

Additional studies:

Comment

Topical steroids versus placebo:

Clinical guide:

Substantive changes

Pimecrolimus

Summary

Benefits

CLEARANCE: Pimecrolimus versus vehicle: