Atopic eczema

Benefits

We found no systematic review of treatment with topical steroids.

Topical steroids versus placebo: We found nine RCTs (double blind vehicle controlled studies) comparing topical steroids versus placebo cream (vehicle) in patients with atopic eczema. Three trials included patients with non-atopic forms of eczema, and another three did not specify the type of eczema. The three remaining trials all found substantial improvement with steroid compared to placebo (table).4^–6

Topical steroids versus each other: We found 11 further double blind RCTs comparing a variety of topical steroids against each other (no placebo) in children and adults with atopic eczema. These showed significant improvements in 41-97% of patients after two to six weeks of treatment.

Harms

No serious or systemic effects or cases of skin atrophy were reported in these short term trials, nor in a longer cohort study in 14 prepubertal children.7 Minor adverse effects such as burning, stinging, irritation, folliculitis, hypertrichosis, contact dermatitis, and pigmentary disturbances occurred in less than 10% of patients.

Skin thinning: We found no RCTs looking at skin thinning in patients with atopic eczema. Four small RCTs in healthy volunteers (n=12) used ultrasound to evaluate skin thickness.8^–11 Skin thinning occurred with three preparations (triamcinolone acetonide 0.1%, clobetasol 17-propionate 0.05%, and betamethasone 17-valerate 0.1%) after twice daily application for six weeks but reversed within four weeks of stopping treatment.

Comment

The RCTs used different clinical scoring systems, making it difficult to compare results.

Benefits

We found no systematic review of the effects of combinations of topical antimicrobials and steroids.

Combinations versus topical steroid alone: We found two RCTs comparing topical antimicrobial-steroid combinations versus topical steroid alone in patients with atopic dermatitis. 12 13 These trials showed no significant difference in the improvement in clinical signs and symptoms with hydrocortisone acetate-fusidic acid compared with hydrocortisone (186 participants) or betamethasone-fusidic acid compared with betamethasone (60 participants) after two weeks' and one week's treatment.

Combinations versus each other: Four further RCTs (34-207 patients) compared different topical steroid-antimicrobial preparations with each other in clinically infected eczema (atopic eczema not specified).14^–17 These found no significant difference between the various preparations with respect to improvement in clinical signs and symptoms. However, patients treated with acetate-fusidic acid responded more quickly than those treated with miconazole-hydrocortisone, and bacteriological responses to betamethasone and acetate-fusidic acid were superior to those with betamethasone-clioquinol and miconazole-hydrocortisone.

Harms

Minor adverse effects—itching, stinging, burning, and irritation—were reported in <2% of patients.

Comment

Only the second study specified a degree of infection in most participants at recruitment. This study also included patients with contact dermatitis in the overall analysis, and the use of left-right comparisons within individual participants may have reduced any observed beneficial effect of combination therapy due to systematic absorption of the antimicrobial agent.13 In practice, topical antimicrobial-steroid combinations are usually reserved for clinically infected eczema.

Benefits

We found no systematic review. We found three controlled trials, one of which did not mention randomisation. A double blind RCT in 48 atopic patients (24 adults and 24 children >7 years old; skin prick and radioallergosorbent test (RAST) status not specified) compared Gore-tex bedcovers, benzyltannate spray, and high filtration vacuuming against cotton bedcovers, placebo spray, and standard vacuum cleaners. After six months there was a significantly greater reduction in eczema severity scores in treated patients than with placebo (mean difference in severity score (maximum 108 units)=4.3 units, 95% confidence interval 1.3 to 7.3). This was associated with a 98% reduction in mean mattress dust load compared with 16% in the placebo group (P=0.002) and a 91% and 76% reduction in the concentration of bedroom and living room carpet mite allergen Der p1 compared with 89% and 38% in the placebo group (P=0.94 and P=0.27).20 A double blind RCT using natamycin or placebo spray with or without vacuuming in 20 patients with atopic dermatitis (aged 12-47 years) with positive skin prick and RAST tests to house dust mite showed no correlation between improvement in clinical score and lowered numbers of mites. However, the study was small and the maximum reduction in mite numbers in mattresses was only 68%.21 A controlled trial (randomisation not mentioned) in patients with atopic eczema showed induction of an itch free period and prolonged remission in 30 patients with positive mite RAST scores after three to four weeks in a “clean room” with reduced dust levels (levels of Der p1 were not measured). Neither an itch free period nor prolonged remission were seen in the 11 patients with negative RAST scores treated in a similar environment, or in the 10 controls with positive mite RAST scores treated in a common hospital room.22

Harms

No harmful effects were reported in the trials.

Comment

Additional, small, uncontrolled studies have suggested a beneficial effect of mite reduction measures on symptoms, although mite or allergen levels were not quantified. The use of bedding covers seems to be the simplest and most effective measure to reduce house dust mite levels in the home.

Benefits

In infants: We found one systematic review that identified one small RCT in 17 breastfed infants with atopic eczema. This looked at the effect of excluding allergenic foods, such as cow's milk and eggs, from the mother's diet. It found no effect on the severity of eczema.23 However, soya milk, which is potentially allergenic itself, was used as a cow's milk substitute in this trial.

In children: We found no systematic review. We found two RCTs (double blind crossover) evaluating the effects of an egg and milk exclusion diet in unselected children with eczema. Both used potentially allergenic soya based milk substitute during the trial period. 24 25 One RCT in 40 children aged 2-8 years found a significant improvement in eczema severity (14/20 treated children improved versus 1/20 controls).24 The other RCT, involving 40 children and young adults, showed no effect.25 Double blind placebo controlled food challenges have been used to identify patients with food allergy, but the clinical relevance of positive reactions (which may comprise gastrointestinal, respiratory, or cutaneous symptoms) to subsequent eczema control is unclear. In three studies, double blind placebo controlled food challenges caused immediate hypersensitivity reactions in 63% of children (n=320) with moderate to severe atopic eczema and in 33-39% of children (n=211) with mild to severe atopic eczema. Egg, milk, and peanut accounted for 67-78% of the reactions. The effect of subsequent dietary elimination was studied in only 27 of these children. This showed a greater improvement in patients on exclusion diets than in non-randomly selected controls, using a crude scoring system.26 Only one RCT (in 85 children) has looked at a “few foods diet,” in which all but a handful of foods are excluded. This found no difference in eczema severity compared with normal diet.

In adults: We found no systematic review. We found one RCT (double blind crossover) that had analysed adults separately. This found no significant improvement in eczema severity with an egg and cow's milk exclusion diet in 18 adults, although potentially allergenic soya milk was used as a cow's milk substitute.25

Harms

Calcium, protein, and calorie deficiency are risks of dairy-free diets in children.

Comment

The clinical relevance to patients of the changes in severity scores obtained in many studies is unknown. We have not included studies looking at the role of food additives, fatty acid supplementation, or trace elements in eczema.

Benefits

We found no systematic review or RCTs. One 17 year prospective study of 236 healthy infants found that those who were breast fed exclusively for more than six months had a significantly lower prevalence of eczema at one year (all infants) and three years (infants with a family history of atopy) than those breast fed for less than one month and weaned onto cow's milk formula.27 Infants who were intermittently breast fed for two to six months showed no reduction in the prevalence of eczema. Two prospective studies 28 29 compared prevalence of eczema in exclusively breast fed infants and in non-breast fed infants. Non-breast fed infants were randomised to different formulae. In infants with a family history of atopy, those who were exclusively breast fed for an average of five months had a significantly lower prevalence of eczema at 18 months compared with non-breast fed infants randomised to soya or cow's milk, but not compared with those randomised to whey hydrolysate or casein hydrolysate. One further prospective study showed a significantly lower incidence of eczema at three years in infants breast fed for 6-13 months (with or without milk supplements) than in those fed conventional adapted formula, but a comparable incidence with those fed hydrolysed milk formulae. Some studies found no beneficial effect of breast feeding, but all had methodological problems.

Harms

We found no evidence of harms associated with prolonged breast feeding.

Comment

Much of the available evidence suffers from methodological difficulties such as selection and information bias, short duration of breast feeding, and inadequate control for confounding factors such as introduction of supplemental milk or solid foods. Choosing to breast feed exclusively for prolonged periods may be associated with other factors that protect against eczema, leading to bias.

Benefits

We found one systematic review that identified three RCTs. 30 These found a lower prevalence of eczema in breast fed infants whose mothers took antigen avoidance diets compared with those on normal diets during lactation.

Harms

No harms of restricting mother's diet during lactation were reported.

Comment

Methodological shortcomings in all three trials argue for caution in applying these results. 30