Dermatitis and Staphylococcus aureus

Among patients with atopic dermatitis, S. aureus is typically found in around 90% of clinically involved skin areas2^,3 and around 75% of clinically uninvolved areas.2 It represents about 90% of the total aerobic bacterial flora in the lesions of such patients compared with 30% in normal skin.2 The density of S. aureus tends to increase with the severity of dermatitic lesions.4 It has been estimated that around 80% of allergic contact dermatitis skin lesions are colonised with S. aureus.5 The consequences of such colonisation, and how 'colonisation' (bacteria present but doing no harm) differs from 'infection' (bacteria causing harm), are not clear. Specific S. aureus infections (such as boils and folliculitis) are more common in patients with atopic dermatitis. These infections often resolve with appropriate antibiotic treatment, suggesting that S. aureus can act as a primary pathogen.

Antistaphylococcal therapy and disease activity

S. aureus can exacerbate the underlying activity of dermatitis or trigger a flare6 (while not causing an overt infection). Accordingly, any treatment that eradicates S. aureus should reduce the severity of the disease activity (but not cure the dermatitis). Short courses of an oral anti-S. aureus antibiotic (e.g. flucloxacillin) are given to manage severe atopic dermatitis which is infected or colonised with bacteria and in dealing with flares which do not respond to other measures. However, a recent randomised placebo-controlled trial suggests that 4 weeks of oral flucloxacillin therapy (250mg four times daily) does not improve the symptoms or the clinical appearance of atopic dermatitis in patients without physical signs of S. aureus infection.7

Long-term use of oral antibiotics increases the likelihood of adverse reactions. Topical antimicrobial therapy would therefore be an attractive alternative for treating skin diseases. In a double-blind crossover trial, 45 patients (aged 2-56 years) with typical features of atopic dermatitis were involved. Patients were randomised to once-daily treatment with mupirocin ointment (an antistaphylococcal antibiotic) or placebo, for 2 weeks.8 Patients applied a standardised dose of topical corticosteroid throughout the trial. Mupirocin caused a short-term reduction in clinical severity (i.e. extent, erythema, pustulation, excoriations, dryness and cracking) compared with placebo.8 However, topical antibiotics are not ideal because of the possibility of the development of resistance. This has therefore led to a search for alternative therapies.

Antiseptics, such as triclosan and benzalkonium chloride, have antibacterial action with less potential for the development of bacterial resistance than with antibiotic therapy. They can also be formulated into bath additives, so facilitating application to large areas of skin. They might therefore offer dual potential for therapeutic advantages over an emollient alone in atopic dermatitis. Firstly, reducing the bacterial load might help prevent S. aureus infections such as boils and folliculitis. Secondly, reduction of secondary pathogen effects might reduce the underlying disease activity. It has also been argued that reducing S. aureus carriage in these patients would help prevent its spread to family members and to other patients at outpatient clinics.

Formulations

Emulsiderm bath additive consists of 0.5% (w/w) benzalkonium chloride in an emollient base. The manufacturer recommends adding 7-30mL of emollient solution to each bath, depending on the size of bath and of the patient. A typical adult bath filled to a depth of 20cm contains around 125L of water: adding 30mL of Emulsiderm results in around a 1:4000 dilution of the product. The manufacturer's in-vitro data suggests that three 30-minute exposures per day are needed to reduce the bacterial count by greater than 95% with a 1:5000 dilution.9 Emulsiderm emollient 0.5% (w/w) is also licensed for direct application to the skin.

Oilatum Plus bath additive contains 6% (w/w) benzalkonium chloride and 2% (w/w) triclosan. The manufacturer recommends that 2 capfuls (20mL) should be added to a typical bath filled to 20cm, producing around a 1:6000 dilution of the product. The manufacturer claims that this dilution is effective against S. aureus in vitro, and that the addition of triclosan should enhance the antibacterial effect. There are no published data available to substantiate these claims.

Dermol 500 lotion contains 0.1% (w/w) benzalkonium chloride and 0.1% (w/w) chlorhexidine hydrochloride. As this product is applied directly to the skin, the antiseptics should be in sufficient concentration to produce effective antistaphylococcal activity but are theoretically more likely to cause irritation.

Clinical trials

There are two published studies of Oilatum Plus,10^,11 one of Dermol 50012 and none of Emulsiderm.

Oilatum Plus

The two small double-blind randomised trials on the clinical10^,11 and antibacterial10 effects of Oilatum emollient versus its antiseptic-containing counterpart Oilatum Plus have been reported only in a "round table" discussion document sponsored by the manufacturers. In both studies, recent or concurrent use of systemic or topical antibacterial therapy or oral corticosteroids was not allowed, but patients applying topical corticosteroids on admission were allowed to continue (but not increase) their use.

The first study involved 15 patients (aged 4-34 years) with moderate or severe atopic dermatitis and S. aureus present on their skin (confirmed microbiologically).10 Patients added 15mL of emollient to their 8-inch-depth, 10-15 minute daily bath for 4 weeks. On comparing the two treatments, the mean changes in clinical scores (of scaling, erythema, oedema, vesicles, crusts, excoriations, lichenification, pigmentation, scratching and loss of sleep) and the population densities of S. aureus were not significantly different after 4 weeks of therapy. This trial was complicated by poor adherence to therapy, with 5 of the 8patients in the Oilatum group failing to complete the study.

The second was a crossover study of Oilatum emollient and Oilatum Plus in 26 children with atopic dermatitis and recurrent infection and/or frequent exacerbations.11 The two 4-week treatment periods were separated by 2 treatment-free weeks. Both the method of emollient application and the measurement of disease activity were the same as in the first trial.10 At 4 weeks, there was a clinical improvement from baseline in the Oilatum Plus group (p<.05) but not in the Oilatum emollient group. However, a comparison of the mean changes in clinical score between the Oilatum group and the Oilatum Plus group would have been more meaningful. Such data were not presented and they are unlikely to have been significantly different. The arguably more important subjective assessments (such as skin condition), rated in the diary cards by the patients' parents, did not show any significant differences between the two treatments.11 Four patients withdrew from the study: 2 for reasons unrelated to the study, 1 (on Oilatum Plus) after experiencing severe pruritus and 1 (on Oilatum) because of deteriorating symptoms.

Dermol 500

In an uncontrolled open-label trial of Dermol 500, 39 children requiring emollients for their eczema/dermatitis were involved.12 For 14 days, Dermol 500 lotion was massaged gently into affected areas (12 of the patients also used the product in the bath, shower or instead of soap). Patients could continue using any other systemic or topical treatment, except for another emollient. Each child's parent/guardian assessed the skin condition by scoring them for skin dryness and severity of itching, and also recorded the ease with which the treatment could be applied. Skin dryness and itching were reportedly improved in around 87% of patients. However, because of the trial design it was not possible to tell whether the antiseptic contained within Dermol 500 provided additional therapeutic activity to ordinary emollients. It is unclear whether the results of such an uncontrolled open-label study could be due to reporting bias, placebo effects or spontaneous improvement.

Lack of useful data

Clinical trials in atopic dermatitis are difficult to carry out, particularly when they may involve assessing a marginal treatment benefit. There tend to be several different components to each patient's therapy and few patients adhere strictly to a treatment regimen. Even so, it is disappointing that the therapeutic potential of emollient/antiseptic combinations has not been investigated more thoroughly. Future studies would need to accurately document topical corticosteroid use, since it is possible that such therapy could contribute to any potential treatment benefits seen with antiseptic emollients.

Unwanted effects

In the absence of large well-controlled studies, it cannot be assumed that any potential benefits of antiseptic emollients outweigh possible unwanted effects (such as allergic contact dermatitis). All emollients can make the bath slippery.

Conclusion

Emollients are useful for patients with inflammatory skin diseases such as atopic dermatitis. Dermol 500, Oilatum Plus and Emulsiderm combine an emollient base with an antiseptic component. Theoretically, their antiseptic activity could offer a therapeutic advantage over ordinary emollients. However, there are very few published data from clinical trials of Dermal 500 lotion and Oilatum Plus emollient and none for Emulsiderm. Therefore, their routine use in patients with atopic dermatitis cannot be recommended.